Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemi...Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.展开更多
Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the char...Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.展开更多
Background:Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to reduce its consequences. This study was aime...Background:Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to reduce its consequences. This study was aimed at determining the activities of new-onset primary Sjögren syndrome (pSS) since the emergence of SARS-CoV-2.Methods:This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group ( n = 24) or vaccinated and infected group based on exposure ( n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS-CoV-2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS-CoV-2 were assigned to a vaccinated and infected group. The controls comprised age- and sex-matched patients who had not been exposed to SARS-CoV-2 before December 2019 ( n = 21). We then compared data among the three groups. Results:The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti-nuclear antibody (ANA) titers > 1:320 ( n = 12;50%) and anti-phospholipid antibodies (aPL) ( n = 7;29%) than the controls. The frequency of anti-Ro/SSA antibodies (13, 65%), ANA titers > 1:320 ( n = 16;80%), and aPLs ( n = 7;29%) ( n = 5;25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups ( p < 0.05, for all). Conclusions:Patients with new-onset pSS and a history of vaccination and SARS-CoV-2 infection展开更多
Background:Sarcopenia significantly impairs quality of life(QoL).The Sarcopenia Quality of Life®(SarQol®)questionnaire provides a sarcopenia-specific instrument for the assessment of QoL.The aim of this stud...Background:Sarcopenia significantly impairs quality of life(QoL).The Sarcopenia Quality of Life®(SarQol®)questionnaire provides a sarcopenia-specific instrument for the assessment of QoL.The aim of this study was to cross-culturally adapt the SarQol®to an Indonesian language questionnaire and to confirm its validity and reliability as a tool to measure QoL in Indonesian-speaking elderly patients with sarcopenia.Methods:This cross-sectional study translated and cross-culturally adapted the SarQol®questionnaire,followed by evaluating the psychometric properties of the final cross-culturally adapted SarQol®Indonesia questionnaire.Results:Fifty-nine elderly Indonesian subjects(29 sarcopenic and 30 nonsarcopenic)with a mean age of 72.2±6.3 years were included in this study.SarQol®Indonesia questionnaire overall provides a good discriminative value[60.61±14.34 vs.73.60±13.17,p=0.001],good internal consistency(Cronbach'sαcoefficient=0.896 and McDonald'sωcoefficient=0.906,both with good correlation to the questionnaire individual domains),acceptable construct validity,and good test-retest reliability(intraclass correlation coefficient:0.962[95%confidence interval:0.883-0.987]).Conclusions:The SarQol®Indonesia questionnaire provides a conceptual and literally equivalent questionnaire content to its original source with good discriminative value,good internal consistency,acceptable construct validity,and good test-retest reliability.The SarQol®Indonesia questionnaire is ready to be used to measure QoL in Indonesian elderly sarcopenic individuals.展开更多
To the Editor,The hypocomplementemic urticarial vasculitis(HUV)is a subtype of urticarial vasculitis.The diagnostics has become easier with the Schwartz criteria proposed in 1982.1,2 It has a large spectrum of etiolog...To the Editor,The hypocomplementemic urticarial vasculitis(HUV)is a subtype of urticarial vasculitis.The diagnostics has become easier with the Schwartz criteria proposed in 1982.1,2 It has a large spectrum of etiology.We report a case of a 43-year-old woman who was admitted to Hedi Chaker University Hospital to explore skin rash and lower limbs pitting edema.She had multiple recurrent urticarial rashes on the trunk and limbs.She also had angioedema affecting the tongue and eyelids,regressing spontaneously.She complained of asthenia,anorexia,and dyspnea on exertion.All was evolving for 4 months.Physical examination showed:fifth proximal interphalangeal arthritis,bilateral lower limb edema,and urticarial exanthema slightly pruritic leaving residual pigmentation on the trunk and limbs.She suffered from impure nephrotic syndrome with microscopic hematuria and acute renal failure(creatinine clearance at 50 mL/min).The levels of C3,C4,and C1q complement fractions were markedly decreased.The anti-C1q antibodies were positive(anti-C1q:99 U/mL,Cut-off titer:15 U/mL).展开更多
To the Editor,Rheumatoid arthritis(RA)synovitis is characterized by synovial inflammation,characterized by synovial proliferation,neovascularization,and leukocyte infiltration into the joint space,1 leading to irrever...To the Editor,Rheumatoid arthritis(RA)synovitis is characterized by synovial inflammation,characterized by synovial proliferation,neovascularization,and leukocyte infiltration into the joint space,1 leading to irreversible cartilage and bone damage.2 This synovial inflammation stimulates the formation of pannus,which is an invasive tumor-like mass,ultimately contributing to the pathogenesis of RA.RA shares several similarities with cancer,including joint pain,swelling,and stiffness,which are accompanied by hypoxia in the synovial tissue and tumor environment.3 Spalt-like transcription factor 4(SALL4)plays an essential role in the occurrence and development of tumors.4 However,SALL4 expression in synovial tissue of RA is yet to be investigated.This study aimed to investigate SALL4 expression in synovial tissue derived from patients with RA,using immunohistochemical techniques.展开更多
To the Editor,Sarcoidosis is a disease known for over a century and remains enigmatic in etiology and pathophysiology.1 While the pulmonary manifestation prevails in more than 90%of cases,sarcoidosis can affect any or...To the Editor,Sarcoidosis is a disease known for over a century and remains enigmatic in etiology and pathophysiology.1 While the pulmonary manifestation prevails in more than 90%of cases,sarcoidosis can affect any organ.Commonly,it targets the eyes,skin,lymph nodes,and,in rare instances,the liver and spleen.2 The development of the disease is significantly influenced by genetic and environmental factors,as well as gene variations on chromosome 6.Notably,first-degree relatives of patients have a heightened risk factor of 3.7.Other adverse prognostic factors involve being of Black race,female gender,and having a lower income.The increased incidence of sarcoidosis among firefighters who responded to the 9/11 disaster highlighted environmental triggers,including agricultural employment,metalworking,firefighting,exposure to inorganic and silica dust,and handling building supplies.1 Clinical symptoms can vary widely depending on the affected organ.Diagnosis often relies on characteristic chest radiography findings,but approximately 10%of patients show noncaseating granulomas on biopsy without pulmonary abnormalities.2 Herein,we present a unique case of multiorgan sarcoidosis,where the sole manifestations were severe thrombocytopenia,weight loss,and a history of cerebral vascular events.展开更多
A 59-year-old woman was admitted to Peking University People's Hospital with a 6-month history of a palpable growing abdominal mass.She had no fever,abdominal pain,hematochezia,or vaginal bleeding but had a 13-yea...A 59-year-old woman was admitted to Peking University People's Hospital with a 6-month history of a palpable growing abdominal mass.She had no fever,abdominal pain,hematochezia,or vaginal bleeding but had a 13-year history of systemic lupus erythematosus,thrombocytopenia,and hypertension.Physical examination showed a large,painless,firm abdominal mass with limited mobility.Complete blood count showed a hemoglobin concentration of 109 g/L,neutrophilic leukocytosis(9.6×10^(9)/L),and thrombocytopenia(47×10^(9)/L).Antinuclear antibodies were present at a titer of 1:640 and antidouble-stranded DNA antibody was positive.Blood tests for carbohydrate antigen(CA)19-9,carcinoembryonic antigen,CA-125,and alpha-fetoprotein were performed:only CA-125 was elevated.The mass measuring 12 cm by 10 cm by 8 cm had been detected by laparoscopy in another hospital 4 months ago.It was tightly associated with the intestine,with tortuous blood vessels on the surface.However,the surgery had not been done because of her low platelets and extremely high bleeding risk.Contrast-enhanced computed tomography revealed an irregular cystic mass,measuring 12.1 cm by 11.2 cm by 14.8 cm(Figure 1A),with heterogeneous enhancement.The cystic mass contained thickened septa.展开更多
Systemic lupus erythematosus(SLE),a chronic autoimmune disease,is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems.Hallmarks of SLE include elevated type I interfe...Systemic lupus erythematosus(SLE),a chronic autoimmune disease,is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems.Hallmarks of SLE include elevated type I interferons and autoantibody production,though the exact causes of SLE remain elusive despite advances in research techniques.Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods.Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression.Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations,oxidative stress,immune metabolic reprogramming,and cellular death.These factors collectively contribute to the loss of self-tolerance,increased autoantibody production,and impaired clearance of immune complexes,leading to their deposition.This triggers sustained inflammatory responses and damages multiple organs.This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE.Targeting mitochondrial pathways presents a promising strategy for treating SLE,potentially improving prognosis and quality of life for those affected.Future research should further investigate the role of mitochondria in the onset and progression of SLE,providing new avenues for understanding and managing this complex disease.展开更多
To the Editor,Anti-melanoma differentiation-associated gene 5(anti-MDA5)antibody-associated dermatomyositis(DM)presenting with rapidly progressive interstitial lung disease(RP-ILD)is extremely challenging to treat.MDA...To the Editor,Anti-melanoma differentiation-associated gene 5(anti-MDA5)antibody-associated dermatomyositis(DM)presenting with rapidly progressive interstitial lung disease(RP-ILD)is extremely challenging to treat.MDA5 is a cytosolic viral RNA sensor that normally triggers an innate response resulting in interferon I production.Upregulation of MDA5 expression can result in autoantibody formation,leading to overactivation of the type I interferon pathway,causing aberrant metabolic remodeling of peripheral B and T cells and a profibrotic response in the affected lungs.展开更多
To the Editor,We present a case involving a 44-year-old male patient who has suffered from psoriasis for over 30 years and developed recurrent pericardial effusions over the past 4 years.Psoriasis has been linked to a...To the Editor,We present a case involving a 44-year-old male patient who has suffered from psoriasis for over 30 years and developed recurrent pericardial effusions over the past 4 years.Psoriasis has been linked to an elevated risk of cardiovascular disease due to the shared interleukin(IL)-23/T helper type 17(Th17)immune pathway.1 Notably,inflammatory cells Th17 are persistently exposed to the pro-inflammatory factor IL-23.The inhibition of downstream effector cytokine IL-17A by secukinumab can mitigate the excessive skin response to inflammatory factors,potentially reducing the cardiovascular risk in psoriasis patients.展开更多
To the Editor,Systemic lupus erythematosus(SLE)is a chronic autoimmune systemic disease in which the immune system attacks healthy cells and tissues throughout the body with a broad variety of clinical manifestations,...To the Editor,Systemic lupus erythematosus(SLE)is a chronic autoimmune systemic disease in which the immune system attacks healthy cells and tissues throughout the body with a broad variety of clinical manifestations,and is more prevalent in African American women and women than in other ethnic minority groups.1 The maximum estimation for the prevalence of SLE in the United States is about 320,000 patients.2 However,the first presentation of SLE often mimics a viral syndrome with constitutional symptoms,like,a low-grade fever,fatigue,and weight loss,and maybe arthralgia or arthritis;it may present in several other ways and have an abrupt onset with target-organ involvement,particularly in Hispanics(61%)and African Americans(45%)compared with Whites(41%).1 Neurological manifestations are common in SLE,named neuropsychiatric SLE,and its prevalence ranges between 14%and 95%,which is more common in children than adults.The involvement of the nervous system is coupled with worse outcomes and mortality rates vary from 2%to 45%.Psychoses,seizures,and cranial nerve involvement,in particular,have been given much emphasis.Besides,visual defects secondary to involvement of the visual pathways posterior to the optic chiasm,presenting as homonymous hemianopia,were rarely reported in SLE.3-5 On the other hand,homonymous hemianopia as the first manifestation of SLE is extremely rare in the literature.In this paper,we present a patient who experienced homonymous hemianopia as the initial presentation of SLE.展开更多
Background:Polymyalgia rheumatica (PMR) is an inflammatory disease that affects the older adult population. The aim of this study was to investigate the risk and prognosis associated with the coronavirus disease 2019 ...Background:Polymyalgia rheumatica (PMR) is an inflammatory disease that affects the older adult population. The aim of this study was to investigate the risk and prognosis associated with the coronavirus disease 2019 (COVID-19) infection among patients diagnosed with PMR during the predominance of the Omicron variant.Methods:In this retrospective study, we included a cohort of patients with PMR who met the 2012 European League Against Rheumatism/American College of Rheumatology classification criteria or the 1982 PMR diagnostic criteria and tracked their progress over time. The diagnosis of COVID-19 was based on the clinical manifestations and laboratory tests. We collected demographic information, PMR disease activity, treatment data, and clinical data related to COVID-19.Results:In total, 101 patients diagnosed with PMR were enrolled. Most patients with PMR exhibited low disease activity. Of the total cohort, 81 patients (80.2%) were categorized as individuals diagnosed with COVID-19, while the remaining 20 (19.8%) were not diagnosed with COVID-19. Among the patients with PMR diagnosed with COVID-19, 65 (80.2%) exhibited the presence of the COVID-19 antigen, while 16 (19.8%) tested positive for COVID-19 RNA. Most COVID-19 patients with PMR were classified as having mild disease (72, 88.9%). Two cases were identified within the confirmed infected group, resulting in a recurrence rate of 2.5% (2/81). Conversely, no relapses were observed in the non-infected group (0/20). In our multivariate logistic regression analysis, we found that pre-COVID-19 PMR disease activity was an independent risk factor for COVID-19 infection (odds ratio = 30.00, 95% confidence interval: 2.137-421.117, p = 0.012). Conclusion:The increased susceptibility to COVID-19 may be influenced by the pre-existing disease activity of PMR.展开更多
To the Editor,Genetic and phenotypic heterogeneity present challenges for the diagnosis and personalized treatment of systemic lupus erythematosus(SLE).1 Leukopenia,a common clinical presentation of SLE,can vary in se...To the Editor,Genetic and phenotypic heterogeneity present challenges for the diagnosis and personalized treatment of systemic lupus erythematosus(SLE).1 Leukopenia,a common clinical presentation of SLE,can vary in severity from mild to severe.Current thinking often attributes the pathogenesis of leukopenia to immune-mediated damage,infections,or iatrogenic factors(azathioprine and cyclophosphamide).2 However,the gene defects associated with leukopenia have only gained limited attention.Here,we report a novel dedicator of cytokinesis 2(DOCK2)gene mutation that played a nonautoimmune pathogenic role in a woman with SLE who developed refractory lymphopenia.展开更多
To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspa...To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspase activation and recruitment domain 15(CARD15).NOD2 mutations result in the activation of nuclear factor-kappa B and induction inflammation.1 Some patients develop the disease in a familial manner,but sporadic cases can occur.The main clinical manifestations of BS are the triad of rash,arthritis,and iridocyclitis,while multiple aortitis,deafness,heart disease,liver,spleen,and central nervous system are also involved.2 The disease was first described by Dr.Blau in 1985.展开更多
To the Editor,Lupus nephritis(LN),a renal symptom of systemic lupus erythematosus(SLE),frequently causes severe organ damage in SLE patients.1 There is no consensus on the definition of refractory LN,which has been su...To the Editor,Lupus nephritis(LN),a renal symptom of systemic lupus erythematosus(SLE),frequently causes severe organ damage in SLE patients.1 There is no consensus on the definition of refractory LN,which has been suggested to occur when remission is not achieved after 3–12 months of combined glucocorticoids and immunosuppressive therapy.2 Podocytic infolding glomerulopathy(PIG),a rare type of glomerular morphological alteration,is primarily characterized by the presence of microspheres,microtubular structures,or a combination of the two,which are associated with podocyte infolding into the glomerular basement membrane(GBM).3,4 The exact pathogenesis of PIG remains unclear,but it may be associated with autoimmune diseases like SLE and Sjögren's syndrome.The occurrence of refractory LN complicated by PIG is rare and poses significant challenges in management.Here,we endeavor to provide the patient with benefits by employing a novel treatment,Telitacicept,which has demonstrated the potential to achieve complete renal remission in such cases.展开更多
To the Editor,Diabetes mellitus(DM)patients have a higher incidence of musculoskeletal issues compared to those without diabetes.With diabetes-related complications increasing,early detection of musculoskeletal diseas...To the Editor,Diabetes mellitus(DM)patients have a higher incidence of musculoskeletal issues compared to those without diabetes.With diabetes-related complications increasing,early detection of musculoskeletal diseases is crucial for better quality of life and reduced morbidity.Limited joint mobility(LJM),also known as diabetic stiff hand or diabetic cheiroarthropathy(DCA),is an often overlooked complication of type 2 DM.It manifests as painless stiffness in hands,restricted joint movement,and tight skin.Contractures in hand joints can spread to major joints like elbows and knees,severely impacting daily tasks and quality of life.Physical examination aids in diagnosing LJM and related rheumatic conditions like scleroderma.展开更多
A 50-year-old male patient with a history of chronic tophaceous gout presented with low back pain and bilateral shoulder,hip,knee,and buttock pain for 1 year.He had nocturnal exacerbations of buttock pain and signific...A 50-year-old male patient with a history of chronic tophaceous gout presented with low back pain and bilateral shoulder,hip,knee,and buttock pain for 1 year.He had nocturnal exacerbations of buttock pain and significant early morning stiffness,which improved with nonsteroidal anti-inflammatory agents(NSAIDs).On examination,he had multiple hard,lobulated tophaceous deposits over the bilateral elbow,hand,leg,and foot.There was no ulcer or discharge from tophi(Figure 1A).He had restriction of movements in the lower back and bilateral positive faber test localized to the back.展开更多
A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manif...A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manifestations of Gottron's sign,V-neck sign,shawl sign,and flagellate erythema(Figure 1A).No interstitial lung disease was detected by high-resolution computed tomography.Comprehensive malignancy screenings,encompassing pap smear and mammogram,endoscopic examination,and computed tomography scans of the thorax,abdomen,and pelvis,were performed.They returned negative,apart from a lobulated nodule with biopsy confirmed as sclerosing pneumocytoma at the left lower lobe(Figure 1C).The therapeutic regimen,consisting of high-dose steroids and mycophenolate mofetil,effectively ameliorated the patient's myositis and rash(Figure 1B).展开更多
In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies th...In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.展开更多
基金R&D program of the Beijing Municipal Education Commission(No.KZ202210025037)Beijing Hospitals Authority Youth Program(No.QMS 20191202).
文摘Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.
基金National Natural Science Foundation of China,Grant/Award Numbers:82071834,82271839,82302047Doctoral Start-up Foundation of Liaoning Province,Grant/Award Numbers:2023−BS-160Dalian Medical University Interdisciplinary Research Cooperation Project Team Funding,Grant/Award Numbers:JCHZ2023010.
文摘Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.
基金Jiangsu Provincial Key Research and Development Program,Grant/Award Number:BE2020621.
文摘Background:Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to reduce its consequences. This study was aimed at determining the activities of new-onset primary Sjögren syndrome (pSS) since the emergence of SARS-CoV-2.Methods:This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group ( n = 24) or vaccinated and infected group based on exposure ( n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS-CoV-2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS-CoV-2 were assigned to a vaccinated and infected group. The controls comprised age- and sex-matched patients who had not been exposed to SARS-CoV-2 before December 2019 ( n = 21). We then compared data among the three groups. Results:The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti-nuclear antibody (ANA) titers > 1:320 ( n = 12;50%) and anti-phospholipid antibodies (aPL) ( n = 7;29%) than the controls. The frequency of anti-Ro/SSA antibodies (13, 65%), ANA titers > 1:320 ( n = 16;80%), and aPLs ( n = 7;29%) ( n = 5;25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups ( p < 0.05, for all). Conclusions:Patients with new-onset pSS and a history of vaccination and SARS-CoV-2 infection
文摘Background:Sarcopenia significantly impairs quality of life(QoL).The Sarcopenia Quality of Life®(SarQol®)questionnaire provides a sarcopenia-specific instrument for the assessment of QoL.The aim of this study was to cross-culturally adapt the SarQol®to an Indonesian language questionnaire and to confirm its validity and reliability as a tool to measure QoL in Indonesian-speaking elderly patients with sarcopenia.Methods:This cross-sectional study translated and cross-culturally adapted the SarQol®questionnaire,followed by evaluating the psychometric properties of the final cross-culturally adapted SarQol®Indonesia questionnaire.Results:Fifty-nine elderly Indonesian subjects(29 sarcopenic and 30 nonsarcopenic)with a mean age of 72.2±6.3 years were included in this study.SarQol®Indonesia questionnaire overall provides a good discriminative value[60.61±14.34 vs.73.60±13.17,p=0.001],good internal consistency(Cronbach'sαcoefficient=0.896 and McDonald'sωcoefficient=0.906,both with good correlation to the questionnaire individual domains),acceptable construct validity,and good test-retest reliability(intraclass correlation coefficient:0.962[95%confidence interval:0.883-0.987]).Conclusions:The SarQol®Indonesia questionnaire provides a conceptual and literally equivalent questionnaire content to its original source with good discriminative value,good internal consistency,acceptable construct validity,and good test-retest reliability.The SarQol®Indonesia questionnaire is ready to be used to measure QoL in Indonesian elderly sarcopenic individuals.
文摘To the Editor,The hypocomplementemic urticarial vasculitis(HUV)is a subtype of urticarial vasculitis.The diagnostics has become easier with the Schwartz criteria proposed in 1982.1,2 It has a large spectrum of etiology.We report a case of a 43-year-old woman who was admitted to Hedi Chaker University Hospital to explore skin rash and lower limbs pitting edema.She had multiple recurrent urticarial rashes on the trunk and limbs.She also had angioedema affecting the tongue and eyelids,regressing spontaneously.She complained of asthenia,anorexia,and dyspnea on exertion.All was evolving for 4 months.Physical examination showed:fifth proximal interphalangeal arthritis,bilateral lower limb edema,and urticarial exanthema slightly pruritic leaving residual pigmentation on the trunk and limbs.She suffered from impure nephrotic syndrome with microscopic hematuria and acute renal failure(creatinine clearance at 50 mL/min).The levels of C3,C4,and C1q complement fractions were markedly decreased.The anti-C1q antibodies were positive(anti-C1q:99 U/mL,Cut-off titer:15 U/mL).
基金Shanxi Provincial Department of Science and Technology(Grant/Award Number:201803D421072).
文摘To the Editor,Rheumatoid arthritis(RA)synovitis is characterized by synovial inflammation,characterized by synovial proliferation,neovascularization,and leukocyte infiltration into the joint space,1 leading to irreversible cartilage and bone damage.2 This synovial inflammation stimulates the formation of pannus,which is an invasive tumor-like mass,ultimately contributing to the pathogenesis of RA.RA shares several similarities with cancer,including joint pain,swelling,and stiffness,which are accompanied by hypoxia in the synovial tissue and tumor environment.3 Spalt-like transcription factor 4(SALL4)plays an essential role in the occurrence and development of tumors.4 However,SALL4 expression in synovial tissue of RA is yet to be investigated.This study aimed to investigate SALL4 expression in synovial tissue derived from patients with RA,using immunohistochemical techniques.
文摘To the Editor,Sarcoidosis is a disease known for over a century and remains enigmatic in etiology and pathophysiology.1 While the pulmonary manifestation prevails in more than 90%of cases,sarcoidosis can affect any organ.Commonly,it targets the eyes,skin,lymph nodes,and,in rare instances,the liver and spleen.2 The development of the disease is significantly influenced by genetic and environmental factors,as well as gene variations on chromosome 6.Notably,first-degree relatives of patients have a heightened risk factor of 3.7.Other adverse prognostic factors involve being of Black race,female gender,and having a lower income.The increased incidence of sarcoidosis among firefighters who responded to the 9/11 disaster highlighted environmental triggers,including agricultural employment,metalworking,firefighting,exposure to inorganic and silica dust,and handling building supplies.1 Clinical symptoms can vary widely depending on the affected organ.Diagnosis often relies on characteristic chest radiography findings,but approximately 10%of patients show noncaseating granulomas on biopsy without pulmonary abnormalities.2 Herein,we present a unique case of multiorgan sarcoidosis,where the sole manifestations were severe thrombocytopenia,weight loss,and a history of cerebral vascular events.
基金National Natural Science Foundation of China,Grant/Award Numbers:82071813 and 82171772.
文摘A 59-year-old woman was admitted to Peking University People's Hospital with a 6-month history of a palpable growing abdominal mass.She had no fever,abdominal pain,hematochezia,or vaginal bleeding but had a 13-year history of systemic lupus erythematosus,thrombocytopenia,and hypertension.Physical examination showed a large,painless,firm abdominal mass with limited mobility.Complete blood count showed a hemoglobin concentration of 109 g/L,neutrophilic leukocytosis(9.6×10^(9)/L),and thrombocytopenia(47×10^(9)/L).Antinuclear antibodies were present at a titer of 1:640 and antidouble-stranded DNA antibody was positive.Blood tests for carbohydrate antigen(CA)19-9,carcinoembryonic antigen,CA-125,and alpha-fetoprotein were performed:only CA-125 was elevated.The mass measuring 12 cm by 10 cm by 8 cm had been detected by laparoscopy in another hospital 4 months ago.It was tightly associated with the intestine,with tortuous blood vessels on the surface.However,the surgery had not been done because of her low platelets and extremely high bleeding risk.Contrast-enhanced computed tomography revealed an irregular cystic mass,measuring 12.1 cm by 11.2 cm by 14.8 cm(Figure 1A),with heterogeneous enhancement.The cystic mass contained thickened septa.
基金Key Research and Development Program of Jiangxi Municipal Science and Technology Department,Grant/Award Number:20192BBGL70024Science and Technology Program of Department of Health of Jiangxi Province,Grant/Award Number:20204254National Key Research and Development Program of China,Grant/Award Number:2021YFC2501304。
文摘Systemic lupus erythematosus(SLE),a chronic autoimmune disease,is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems.Hallmarks of SLE include elevated type I interferons and autoantibody production,though the exact causes of SLE remain elusive despite advances in research techniques.Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods.Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression.Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations,oxidative stress,immune metabolic reprogramming,and cellular death.These factors collectively contribute to the loss of self-tolerance,increased autoantibody production,and impaired clearance of immune complexes,leading to their deposition.This triggers sustained inflammatory responses and damages multiple organs.This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE.Targeting mitochondrial pathways presents a promising strategy for treating SLE,potentially improving prognosis and quality of life for those affected.Future research should further investigate the role of mitochondria in the onset and progression of SLE,providing new avenues for understanding and managing this complex disease.
文摘To the Editor,Anti-melanoma differentiation-associated gene 5(anti-MDA5)antibody-associated dermatomyositis(DM)presenting with rapidly progressive interstitial lung disease(RP-ILD)is extremely challenging to treat.MDA5 is a cytosolic viral RNA sensor that normally triggers an innate response resulting in interferon I production.Upregulation of MDA5 expression can result in autoantibody formation,leading to overactivation of the type I interferon pathway,causing aberrant metabolic remodeling of peripheral B and T cells and a profibrotic response in the affected lungs.
基金GuangDong Basic and Applied Basic Research Foundation of Guangdong Province,China,Grant/Award Number:2019A1515011094GuangDong Basic and Applied Basic Research Foundation of Guangdong Province,China,Grant/Award Number:2022A1515010471Guangzhou Science and Technology Planning Project of Guangdong Province,China,Grant/Award Number:202102010139.
文摘To the Editor,We present a case involving a 44-year-old male patient who has suffered from psoriasis for over 30 years and developed recurrent pericardial effusions over the past 4 years.Psoriasis has been linked to an elevated risk of cardiovascular disease due to the shared interleukin(IL)-23/T helper type 17(Th17)immune pathway.1 Notably,inflammatory cells Th17 are persistently exposed to the pro-inflammatory factor IL-23.The inhibition of downstream effector cytokine IL-17A by secukinumab can mitigate the excessive skin response to inflammatory factors,potentially reducing the cardiovascular risk in psoriasis patients.
文摘To the Editor,Systemic lupus erythematosus(SLE)is a chronic autoimmune systemic disease in which the immune system attacks healthy cells and tissues throughout the body with a broad variety of clinical manifestations,and is more prevalent in African American women and women than in other ethnic minority groups.1 The maximum estimation for the prevalence of SLE in the United States is about 320,000 patients.2 However,the first presentation of SLE often mimics a viral syndrome with constitutional symptoms,like,a low-grade fever,fatigue,and weight loss,and maybe arthralgia or arthritis;it may present in several other ways and have an abrupt onset with target-organ involvement,particularly in Hispanics(61%)and African Americans(45%)compared with Whites(41%).1 Neurological manifestations are common in SLE,named neuropsychiatric SLE,and its prevalence ranges between 14%and 95%,which is more common in children than adults.The involvement of the nervous system is coupled with worse outcomes and mortality rates vary from 2%to 45%.Psychoses,seizures,and cranial nerve involvement,in particular,have been given much emphasis.Besides,visual defects secondary to involvement of the visual pathways posterior to the optic chiasm,presenting as homonymous hemianopia,were rarely reported in SLE.3-5 On the other hand,homonymous hemianopia as the first manifestation of SLE is extremely rare in the literature.In this paper,we present a patient who experienced homonymous hemianopia as the initial presentation of SLE.
基金Natural Science Foundation of China,Grant/Award Number:82171768National Key Research and Development Program of China,Grant/Award Number:2022YFC3602000Zhejiang Province Excellent Young Talent Fund for Traditional Chinese Medicine,Grant/Award Number:2022ZQ051.
文摘Background:Polymyalgia rheumatica (PMR) is an inflammatory disease that affects the older adult population. The aim of this study was to investigate the risk and prognosis associated with the coronavirus disease 2019 (COVID-19) infection among patients diagnosed with PMR during the predominance of the Omicron variant.Methods:In this retrospective study, we included a cohort of patients with PMR who met the 2012 European League Against Rheumatism/American College of Rheumatology classification criteria or the 1982 PMR diagnostic criteria and tracked their progress over time. The diagnosis of COVID-19 was based on the clinical manifestations and laboratory tests. We collected demographic information, PMR disease activity, treatment data, and clinical data related to COVID-19.Results:In total, 101 patients diagnosed with PMR were enrolled. Most patients with PMR exhibited low disease activity. Of the total cohort, 81 patients (80.2%) were categorized as individuals diagnosed with COVID-19, while the remaining 20 (19.8%) were not diagnosed with COVID-19. Among the patients with PMR diagnosed with COVID-19, 65 (80.2%) exhibited the presence of the COVID-19 antigen, while 16 (19.8%) tested positive for COVID-19 RNA. Most COVID-19 patients with PMR were classified as having mild disease (72, 88.9%). Two cases were identified within the confirmed infected group, resulting in a recurrence rate of 2.5% (2/81). Conversely, no relapses were observed in the non-infected group (0/20). In our multivariate logistic regression analysis, we found that pre-COVID-19 PMR disease activity was an independent risk factor for COVID-19 infection (odds ratio = 30.00, 95% confidence interval: 2.137-421.117, p = 0.012). Conclusion:The increased susceptibility to COVID-19 may be influenced by the pre-existing disease activity of PMR.
基金Natural Science Foundation of Shandong Province(No.ZR2022MH016)National Natural Science Foundation of China(Youth fund project,No.82201994).
文摘To the Editor,Genetic and phenotypic heterogeneity present challenges for the diagnosis and personalized treatment of systemic lupus erythematosus(SLE).1 Leukopenia,a common clinical presentation of SLE,can vary in severity from mild to severe.Current thinking often attributes the pathogenesis of leukopenia to immune-mediated damage,infections,or iatrogenic factors(azathioprine and cyclophosphamide).2 However,the gene defects associated with leukopenia have only gained limited attention.Here,we report a novel dedicator of cytokinesis 2(DOCK2)gene mutation that played a nonautoimmune pathogenic role in a woman with SLE who developed refractory lymphopenia.
基金Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority,Grand/Award Number:XTCX201819National Regional Medical Center Opening Project,Grand/Award Number:NRMC0110BCH Young Investigator Program(BCHYIP),Grant/Award Number:BCHYIP-3-39.
文摘To the Editor,Blau syndrome(BS)is a rare autosomal dominant disorder that occurs early in childhood.It is caused by mutations in nucleotide-binding oligomerization domain-containing protein 2(NOD2),also known as caspase activation and recruitment domain 15(CARD15).NOD2 mutations result in the activation of nuclear factor-kappa B and induction inflammation.1 Some patients develop the disease in a familial manner,but sporadic cases can occur.The main clinical manifestations of BS are the triad of rash,arthritis,and iridocyclitis,while multiple aortitis,deafness,heart disease,liver,spleen,and central nervous system are also involved.2 The disease was first described by Dr.Blau in 1985.
基金National Key Research and Development Program of China(2021YFC2501304)Science and Technology Program of Department of Health of Jiangxi Province(20204254)Key Research and Development Program of Jiangxi Municipal Science and Technology Department(20192BBGL70024).
文摘To the Editor,Lupus nephritis(LN),a renal symptom of systemic lupus erythematosus(SLE),frequently causes severe organ damage in SLE patients.1 There is no consensus on the definition of refractory LN,which has been suggested to occur when remission is not achieved after 3–12 months of combined glucocorticoids and immunosuppressive therapy.2 Podocytic infolding glomerulopathy(PIG),a rare type of glomerular morphological alteration,is primarily characterized by the presence of microspheres,microtubular structures,or a combination of the two,which are associated with podocyte infolding into the glomerular basement membrane(GBM).3,4 The exact pathogenesis of PIG remains unclear,but it may be associated with autoimmune diseases like SLE and Sjögren's syndrome.The occurrence of refractory LN complicated by PIG is rare and poses significant challenges in management.Here,we endeavor to provide the patient with benefits by employing a novel treatment,Telitacicept,which has demonstrated the potential to achieve complete renal remission in such cases.
文摘To the Editor,Diabetes mellitus(DM)patients have a higher incidence of musculoskeletal issues compared to those without diabetes.With diabetes-related complications increasing,early detection of musculoskeletal diseases is crucial for better quality of life and reduced morbidity.Limited joint mobility(LJM),also known as diabetic stiff hand or diabetic cheiroarthropathy(DCA),is an often overlooked complication of type 2 DM.It manifests as painless stiffness in hands,restricted joint movement,and tight skin.Contractures in hand joints can spread to major joints like elbows and knees,severely impacting daily tasks and quality of life.Physical examination aids in diagnosing LJM and related rheumatic conditions like scleroderma.
文摘A 50-year-old male patient with a history of chronic tophaceous gout presented with low back pain and bilateral shoulder,hip,knee,and buttock pain for 1 year.He had nocturnal exacerbations of buttock pain and significant early morning stiffness,which improved with nonsteroidal anti-inflammatory agents(NSAIDs).On examination,he had multiple hard,lobulated tophaceous deposits over the bilateral elbow,hand,leg,and foot.There was no ulcer or discharge from tophi(Figure 1A).He had restriction of movements in the lower back and bilateral positive faber test localized to the back.
文摘A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manifestations of Gottron's sign,V-neck sign,shawl sign,and flagellate erythema(Figure 1A).No interstitial lung disease was detected by high-resolution computed tomography.Comprehensive malignancy screenings,encompassing pap smear and mammogram,endoscopic examination,and computed tomography scans of the thorax,abdomen,and pelvis,were performed.They returned negative,apart from a lobulated nodule with biopsy confirmed as sclerosing pneumocytoma at the left lower lobe(Figure 1C).The therapeutic regimen,consisting of high-dose steroids and mycophenolate mofetil,effectively ameliorated the patient's myositis and rash(Figure 1B).
基金National Institute of Allergy and Infectious Diseases,Grant/Award Numbers:AI101981,AI110498National Institute of Arthritis and Musculoskeletal and Skin Diseases,Grant/Award Numbers:AR079369,AR051749,AR078268,AR075033,AR076450,AR071321,AR065466。
文摘In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.
