疱液在诊断表皮下自身免疫性大疱病中的意义

目的：探讨表皮下自身免疫性大疱病疱液中抗基底膜带（ＢＭＺ）自身抗体的情况及在诊断中的意义。方法：应用非盐裂皮肤及盐裂皮肤间接免疫荧光技术（ＩＦ）检测３８例表皮下自身免疫性大疱病患者疱液和血清中ＩｇＧ、ＩｇＡ、ＩｇＭ、ＩｇＥ及ＩｇＧ亚型ＩｇＧ１～ＩｇＧ４抗ＢＭＺ抗体及滴度，并检测疱液和血清中结合补体Ｃ３的特异性抗ＢＭＺ抗体。结果：（１）疱液和血清中抗ＢＭＺ抗体及滴度和结合补体Ｃ３的特异性抗ＢＭＺ抗体均无显著性差异。（２）大疱性类天疱疮患者的疱液和血清中ＩｇＧ抗ＢＭＺ抗体的亚型分布相同，主要为ＩｇＧ１和ＩｇＧ４。结论：疱液可作为ＩＩＦ检测表皮下大疱病抗ＢＭＺ抗体的另一个有价值的标本来源。     

Differential anti-Golgi complex autoantibody production following murine lactate dehydrogenase-elevating virus infection

Lactate dehydrogenase-elevating virus (LDV) causes asymptomatic infection and persistent viremia in mice with unique infectious specificity directed to a certain subpopulation of macrophages leading to chronic infection and an immunological disorder that includes hyperimmunoglobulinemia and production of autoantibodies. Infection with a species of LDV originally isolated from mice carrying an LDV-contaminated transplantable tumor (LDV-W) was reported to induce anti-Golgi complex antibody (AGA) production. In contrast, infection with the most common LDV species (LDV-P) was not associated with AGA production. Here we performed the first independent side by side comparison of the effects of the two LDV strains on their hosts as an initial approach to investigating the production of AGA. After viral inoculation, both LDV-W and LDV-P infected mice exhibited similar changes in lactate dehydrogenase in plasma suggesting similar viral activity. However, AGA production was observed in only the LDV-W infected mice and these mice exhibited plasma IgG elevation and immune complex formation. These data validated the differential potential of LDV-W and LDV-P in the production of AGA. Future comparative characterizations in the immune processing of Golgi complex autoantigens using these viral strains may be useful in obtaining specific insights in the specific anti-Golgi complex autoimmune responses.     

Systemic Lupus Erythematosus Involving the Nervous System: Presentation,Pathogenesis, and Management

Neuropsychiatric syndromes in systemic lupus erythematosus (SLE) have a wide range of severity and phenotype and are fairly common. Presentations are seen involving both central and peripheral nervous systems. Pathogenic mechanisms are thought to include vascular occlusion and hemorrhage, antineuronal antibodies, cytokine effects, choroid plexus dysfunction, neuroendocrine-immune effects, and direct central nervous system (CNS) tissue injury. Work-up includes serum, cerebrospinal fluid (CSF), and imaging studies. Treatment is based on severity and phenotype and includes steroids, anticoagulants, antidepressants, and cytotoxic approaches. Much remains to be done in terms of further elucidation of pathologic processes, correlation of these mechanisms with specific phenotypes, and management of the most severe presentations of neuropsychiatric lupus erythematosus.     

Natural Autoantibody to Galectin-9 in Normal Human Sera

Antibodies to certain self-antigens are detected in normal individuals as well as in patients with autoimmune diseases. Natural autoantibodies found in normal human sera are thought to act as an immune regulator, a functional controller of specific proteins, or the first-line defense against pathogenic microorganisms. In the course of screening human pancreatic islet cDNA library with human sera, we found that autoantibodies to galectin-9 and its unique isoform are present in normal healthy individuals. Galectin-9 antibody was detected in all 44 human sera tested by the immunoprecipitation assays, suggesting a widespread presence of galectin-9 autoantibodies in humans. The reactivity of the sera to galectin-9 was not inhibited by lactose or endoglycosidase treatment, indicating that the reactivity was not due to a nonspecific lectin–carbohydrate interaction. We also demonstrated by RT-PCR that galectin-9 and its isoform are expressed in a variety of human tissues such as pancreatic islets, liver, lung, and tonsils as well as HeLa and Jurkat cell lines. Thus, although it has been reported previously that human galectin-9 is expressed mainly in immune cells and tissues, the current work suggests that the expression of galectin-9 and its isoform is not tissue-restricted and natural autoantibodies against them are present in normal human sera. The significance of these autoantibodies needs to be studied further.     

Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW × C57BL/6)F1 mice

In the present study, we mapped the major quantitative trait loci (QTL) differing between the NZW and C57BL / 6 inbred strains of mice by making use of (NZW × C57BL / 6.Yaa)F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa. Linkage analysis of 126 C57BL / 6 × (NZW × C57BL / 6.Yaa)F1 backcross males provided evidence for a major QTL on chromosome 7 controlling both the severity of glomerulonephritis and the production of IgG anti-DNA autoantibody and retroviral gp70-anti-gp70 immune complexes. Two additional QTL of C57BL / 6 origin on chromosome 17 had no apparent individual effects, but showed strong epistatic interaction with chromosome 7 QTL for disease severity and anti-DNA autoantibody production. Our data also identified on chromosome 13 a QTL of NZW origin with a major effect on the level of gp70, and showing an additive effect with the chromosome 7 QTL on the level of gp70 immune complexes. Our study thus provides a model to dissect the complex genetic interactions that result in manifestations of murine lupus-like disease.     

Correlation between chlamydial infection and autoimmune response: molecular mimicry between RNA polymerase major σ subunit from Chlamydia trachomatis and human L7

L7 is one of the ribosomal proteins frequently targeted by autoantibodies in rheumatic autoimmune diseases. A computer search revealed a region within the immunodominant epitope of L7 (peptide II) that is highly homologous to amino acid sequence 264 – 286 of the RNA polymerase major σ factor of the eubacterium Chlamydia trachomatis. Anti-L7 autoantibodies affinity purified from the immunodominant epitope were able to recognize this sequence as they reacted with purified recombinant σ factor. Immunofluorescence labeling experiments on C. trachomatis lysates revealed a punctate staining pattern of numerous spots when incubated with the affinity-purified anti-peptide II autoantibodies. Binding of autoantibodies to peptide II was inhibited by the homologous σ peptide. This is the first demonstration of epitope mimicry between a human and a chlamydial protein on the level of B cells. Antibody screening revealed a significant correlation between the presence of anti-L7 autoantibodies and C. trachomatis infection in patients with systemic lupus erythematosus and mixed connective tissue disease. Our results suggest that molecular mimicry is involved in the initiation of anti-L7 autoantibody response and may represent a first glance into the immunopathology of Chlamydia with respect to systemic rheumatic diseases.     

CD40-mediated stimulation of B1 and B2 cells: implication in autoantibody production in murine lupus

B1 cells usually show preferential responses to T cell-independent antigens. To ask whether B1 cells could respond to CD40-mediated stimulation for proliferation and differentiation, and whether CD40-mediated signals are involved in the production of autoantibodies by B1 cells, we compared responses to our newly established agonistic anti-mouse CD40 monoclonal antibody (mAb) between B1 and B2 cells from autoimmune-prone (NZB X NZW) F1 mice. Stimulation with this mAb induced a similar level of proliferative responses of both B1 and B2 cells, as well as an increase in expression of cell surface molecules I-A, CD54, CD23, CD80, and CD86. While co-stimulation with interleukin (IL)-4 markedly augmented proliferative as well as IgG1 and IgE antibody responses of both B1 and B2 cells, co-stimulation with IL-5 augmented proliferative and IgM antibody responses of only B1 cells. Splenic B1, but not B2 cells from young (NZB X NZW) F1 mice spontaneously produced substantial amounts of IgM including IgM anti-DNA antibodies, and the levels increased in case of stimulation with anti-CD40 mAb alone, or to a greater extent with the mAb plus IL-4 and IL-5. Collectively, these results indicate that splenic B1 cells from autoimmune (NZB X NZW) F1 mice have a comparable responsiveness to the CD40-mediated stimulation to that of B2 cells, which would be a potent regulatory mechanism involved in the spontaneous production of autoantibodies by B1 cells.     

Positive direct antiglobulin tests in cancer patients on immune checkpoint inhibitors: A case series from India

Tumour cells activate immune checkpoints such as programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) signalling pathways to inhibit T lymphocyte activation and thus escape from immune surveillance. Immune checkpoint inhibitors (ICPis) reactivate T lymphocytes to recognize cancer cells by blocking CTLA-4 or PD-1. Autoimmune haemolytic anaemia is a rare, but often severe, complication of ICPis. Therefore, we performed a retrospective clinical case review, including serologic, haematology, and biochemistry laboratory results, of three patients who developed autoantibodies to erythrocytes following treatment with pembrolizumab, an anti-PD-1 inhibitor. Serologic testing of blood samples from these patients showed their red cells were positive for direct antiglobulin test (DAT + for IgG in two cases and IgG with C3d in one case). Antibody detection test was negative. No patient had clinical and laboratory features of haemolysis. There were no additional immune-related adverse events. IgG antibodies coating red cells were neither IgG1 nor IgG3 in class and elution was found negative in all. In conclusion, immunohaematology laboratories should be aware of the possibility of erythroid autoantibodies and their nature in cancer patients receiving ICPis. The result of a positive DAT should be interpreted carefully in these patients to exclude other possible causes of anaemia.     

新型冠状病毒感染诱导的机体自身免疫

新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）感染不仅严重影响人体免疫，而且可能诱发易感人群的自身免疫病。此文对SARS-CoV-2感染者体内产生的5大类自身抗体以及这些自身抗体可能导致的自身免疫病、患者自身免疫系统过度激活的相关研究进展，以及其诱导机体自身免疫的可能机制进行综述，以期为SARS-CoV-2相关的自身免疫性损伤与疾病的研究提供理论基础。     

Loss of anti-AT1R reactivity in ELISA post-adsorption – False reactivity or interference in the assay?

Autoantibodies to Angiotensin II type 1 receptor (AT1R) are associated with detrimental outcomes in organ transplants. However, reports showed that adsorption with latex beads reduced positive anti-AT1R antibodies, suggesting possible false reactivity. To investigate this conundrum, we studied 11 samples positive for AT1R antibodies with an ELISA kit before and after adsorption. Adsorption significantly reduced the measurable level of AT1R antibodies (28.3 ± 9.8 vs. 6.3 ± 3.0 U/ml, p < 0.001). AT1R antibodies were lower when post-adsorption serum was added back at 1:1 ratio to the neat serum compared to the diluent control (8.6 ± 4.2 vs. 18.1 ± 10.3 U/ml, p = 0.02). Sham adsorption with the buffer from Adsorb Out™ kit without beads also suppressed the detection of anti-AT1R antibodies (32.7 ± 9.1 vs. 8.1 ± 3.9 U/ml, p < 0.001). Thus, rather than actively removing nonspecific antibodies by the beads, the adsorption process introduces soluble factors that interfere with the detection of anti-AT1R antibodies with the ELISA kit.