Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic he...Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed. Results The median time of onset was 42 days after HSCT （range 16-150 days） and the median duration of HC was 43 days （range 29-47 days）. All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus （CMV） reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy. Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission. Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.展开更多
In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well e...In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well established,their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion.Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases.The following topics will be specifically focused upon:(1)definition and characterization of MDSCs;(2)whether all MDSC populations consist of immature cells;(3)technical issues in MDSC isolation,estimation and characterization;(4)the origin of MDSCs and their anatomical distribution in health and disease;(5)mediators of MDSC expansion and accumulation;(6)factors that determine the expansion of one MDSC population over the other;(7)the Yin and Yang roles of MDSCs.Moreover,the functions of MDSCs will be addressed throughout the text.展开更多
Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitizati...Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies(DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.展开更多
Recurrent spontaneous abortion(RSA),defined as three or more consecutive pregnancy losses before 20 weeks of gestation,is difficult to treat in the clinical setting.It affects 1%–5%of women of reproductive age.In the...Recurrent spontaneous abortion(RSA),defined as three or more consecutive pregnancy losses before 20 weeks of gestation,is difficult to treat in the clinical setting.It affects 1%–5%of women of reproductive age.In the investigations of immunopathogenesis,diagnosis,and treatment of RSA since the late 1980s,it was found that RSA was associated with abnormal maternal local or systemic immune response.The pathogenesis of autoimmune RSA was mainly associated with antiphospholipid antibody(APA),while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance.Systemic etiological screening process and diagnosis systems of RSA with immune type were developed,and anticardiolipin(ACL or ACA)+anti-β2-GP1 antibody combining multiple assays for effective diagnosis of RSA with autoimmune type was first established.According to the dynamic monitoring of clinical parameters before and during gestation,low-dose,short-course,and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were carried out.The outcomes of the offsprings of patients with RSA were followed up,and the safety and validity of the therapies were confirmed.The research achievement leads to great progress in the diagnosis and treatment of RSA in China.展开更多
Objective To investigate the effects of allograft inflammatory factor-1 （AIF-1） and （RANTES） in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and decid...Objective To investigate the effects of allograft inflammatory factor-1 （AIF-1） and （RANTES） in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and deciduas/endometria of 43 unexplained early spontaneous abortion women （group A）, 40 healthy women with early pregnancy（group B） and 20 healthy women with no pregnancy （group C）. Immunohistochemistry and enzyme linked immunosorbent assay （ELISA） were used in this study. Results AIF-1 protein was expressed both in deciduas of group A and in endometria of group C. In group A, H scores in the recurrent abortion deciduas specimens were significantly greater than those in the first abortion;in endometrium, expression of AIF-1 was greater in the secretory than in proliferative phase of group C. In group B, concentrations of RANTES in sera were higher in 7th-8th week of pregnancy than in 6th-7th and 〉8th week of pregnancy; expression of AIF-1 protein showed a negative correlation with RASNTES concentration; a significant increase of the RANTES levels in sera and tissue was observed in group B. Conclusion These results demonstrate, for the first time, that AIF-1 are expressed in deciduas of unexplained spontaneous abortion suggesting that AIF-1 involve in alloimmune abortion; RANTES might act as a novel blocking antibody;AIF-1 and RANTES might act as reliable markers for diagnosis of early alloimmune abortion.展开更多
Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloim...Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy.Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal alloimmunization.FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage.Proper diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies.Given the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT.The aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.展开更多
CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about it...CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre re-combinase in T cells（CD4-Cre+）.T cell-specific deficient of CD98hc resulted in lower responses to alloantigen stimulation in mixed lymphocyte reaction assay.Heterotopic cardiac grafting was then performed from BALB/c（H-2K<sup>d</sup>） to CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> /C57BL/6（H-2K<sup>b</sup>） or control littermate C57BL/6 （B6） mice.We found that all CD98hc<sup>lox/</sup>-CD4-Cre<sup>+</sup> recipients had indefinite survival（MST:】100days, n=8）.In contrast,all littermate B6 recipients suffered acute rejection[MST:（7.4±0.5）d,n=12].In addition,the survival of the skin grafts from donor BALB/c mice to more than postoperative day （POD） 100 heart-bearing tolerant CD98hc<sup>lox/-</sup>CD4- Cre<sup>+</sup> recipients was significantly prolonged[MST: （15.2±2.2）d,n =5]compared that of the B6 mice [MST:（8.2±1.3）d,n=9].In consistent with graft survival, we found that the graft infiltration cells on POD7 were fewer than that of the B6 mice by FACS and immune-staining analysis.Also chemotaxis assay data revealed that the migrated CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> lymphocyte were less than that of B6 in the presence of different concentration of chemokines CCL2, CCL5,and CCL2 plus CCL5.In addition,a neutralizing antibody（clone 26-24）specific against CD98hc prolonged the graft survival[MST:（13.4±2.7）d,n=8; P=0.001]in the B6 recipients after they received the BALB/c mice heart.Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens and decreased migration ability result in ind展开更多
Fetoneonatal alloimmune thrombocytopenia is an infrequent and severe disease that is unexpectedly found after an uncomplicated first pregnancy. Affected infants might show unexplained purpura, intracranial hemorrhage,...Fetoneonatal alloimmune thrombocytopenia is an infrequent and severe disease that is unexpectedly found after an uncomplicated first pregnancy. Affected infants might show unexplained purpura, intracranial hemorrhage, and/or gastrointestinal or genitourinary hemorrhage. Nevertheless, in asymptomatic newborns the thrombocytopenia may be discovered incidentally. We describe a case report that highlights that the incidental diagnosis of FNAIT allows both properly managing the newborn, and detecting maternal anti-HPA1a antibodies in order to prevent the disease in subsequent pregnancies. A non-invasive treatment based on IVIgG allowed to this patient to prevent FNAIT in her second pregnancy.展开更多
文摘Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed. Results The median time of onset was 42 days after HSCT （range 16-150 days） and the median duration of HC was 43 days （range 29-47 days）. All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus （CMV） reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy. Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission. Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.
文摘In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well established,their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion.Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases.The following topics will be specifically focused upon:(1)definition and characterization of MDSCs;(2)whether all MDSC populations consist of immature cells;(3)technical issues in MDSC isolation,estimation and characterization;(4)the origin of MDSCs and their anatomical distribution in health and disease;(5)mediators of MDSC expansion and accumulation;(6)factors that determine the expansion of one MDSC population over the other;(7)the Yin and Yang roles of MDSCs.Moreover,the functions of MDSCs will be addressed throughout the text.
文摘Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies(DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.
基金supported by the National Natural Science Foundation of China(Grant Nos.30730087,30530740,389073,39470722,39870666,39870775,30471822,and 30672231).
文摘Recurrent spontaneous abortion(RSA),defined as three or more consecutive pregnancy losses before 20 weeks of gestation,is difficult to treat in the clinical setting.It affects 1%–5%of women of reproductive age.In the investigations of immunopathogenesis,diagnosis,and treatment of RSA since the late 1980s,it was found that RSA was associated with abnormal maternal local or systemic immune response.The pathogenesis of autoimmune RSA was mainly associated with antiphospholipid antibody(APA),while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance.Systemic etiological screening process and diagnosis systems of RSA with immune type were developed,and anticardiolipin(ACL or ACA)+anti-β2-GP1 antibody combining multiple assays for effective diagnosis of RSA with autoimmune type was first established.According to the dynamic monitoring of clinical parameters before and during gestation,low-dose,short-course,and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were carried out.The outcomes of the offsprings of patients with RSA were followed up,and the safety and validity of the therapies were confirmed.The research achievement leads to great progress in the diagnosis and treatment of RSA in China.
文摘Objective To investigate the effects of allograft inflammatory factor-1 （AIF-1） and （RANTES） in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and deciduas/endometria of 43 unexplained early spontaneous abortion women （group A）, 40 healthy women with early pregnancy（group B） and 20 healthy women with no pregnancy （group C）. Immunohistochemistry and enzyme linked immunosorbent assay （ELISA） were used in this study. Results AIF-1 protein was expressed both in deciduas of group A and in endometria of group C. In group A, H scores in the recurrent abortion deciduas specimens were significantly greater than those in the first abortion;in endometrium, expression of AIF-1 was greater in the secretory than in proliferative phase of group C. In group B, concentrations of RANTES in sera were higher in 7th-8th week of pregnancy than in 6th-7th and 〉8th week of pregnancy; expression of AIF-1 protein showed a negative correlation with RASNTES concentration; a significant increase of the RANTES levels in sera and tissue was observed in group B. Conclusion These results demonstrate, for the first time, that AIF-1 are expressed in deciduas of unexplained spontaneous abortion suggesting that AIF-1 involve in alloimmune abortion; RANTES might act as a novel blocking antibody;AIF-1 and RANTES might act as reliable markers for diagnosis of early alloimmune abortion.
基金This work was supported by Canadian Institutes of Health Research(MOP 68986,MOP 119551,MOP 97918,and 119540)。
文摘Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy.Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal alloimmunization.FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage.Proper diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies.Given the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT.The aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.
文摘CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre re-combinase in T cells（CD4-Cre+）.T cell-specific deficient of CD98hc resulted in lower responses to alloantigen stimulation in mixed lymphocyte reaction assay.Heterotopic cardiac grafting was then performed from BALB/c（H-2K<sup>d</sup>） to CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> /C57BL/6（H-2K<sup>b</sup>） or control littermate C57BL/6 （B6） mice.We found that all CD98hc<sup>lox/</sup>-CD4-Cre<sup>+</sup> recipients had indefinite survival（MST:】100days, n=8）.In contrast,all littermate B6 recipients suffered acute rejection[MST:（7.4±0.5）d,n=12].In addition,the survival of the skin grafts from donor BALB/c mice to more than postoperative day （POD） 100 heart-bearing tolerant CD98hc<sup>lox/-</sup>CD4- Cre<sup>+</sup> recipients was significantly prolonged[MST: （15.2±2.2）d,n =5]compared that of the B6 mice [MST:（8.2±1.3）d,n=9].In consistent with graft survival, we found that the graft infiltration cells on POD7 were fewer than that of the B6 mice by FACS and immune-staining analysis.Also chemotaxis assay data revealed that the migrated CD98hc<sup>lox/-</sup>CD4-Cre<sup>+</sup> lymphocyte were less than that of B6 in the presence of different concentration of chemokines CCL2, CCL5,and CCL2 plus CCL5.In addition,a neutralizing antibody（clone 26-24）specific against CD98hc prolonged the graft survival[MST:（13.4±2.7）d,n=8; P=0.001]in the B6 recipients after they received the BALB/c mice heart.Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens and decreased migration ability result in ind
文摘Fetoneonatal alloimmune thrombocytopenia is an infrequent and severe disease that is unexpectedly found after an uncomplicated first pregnancy. Affected infants might show unexplained purpura, intracranial hemorrhage, and/or gastrointestinal or genitourinary hemorrhage. Nevertheless, in asymptomatic newborns the thrombocytopenia may be discovered incidentally. We describe a case report that highlights that the incidental diagnosis of FNAIT allows both properly managing the newborn, and detecting maternal anti-HPA1a antibodies in order to prevent the disease in subsequent pregnancies. A non-invasive treatment based on IVIgG allowed to this patient to prevent FNAIT in her second pregnancy.
