子宫内膜异位症和流产及不孕患者血清12种自身抗体的分析

检测69例健康孕妇和225例子宫内膜异位症(EMT)、流产和不孕患者血清中 EMAb、ANA、A-dsDNA、A-Sm、A-RNP、A-TG、A-TM、RF、AphA、InAb、CaMAb、ANCA 等12种自身抗体,健康孕妇 EMAb 阳性率为1.4%,其他抗体的总阳性率为4.3%;EMT(n=66)、流产(n=87)和不孕(n=72)组患者 EMAb 阳性率分别为72.7%、37.9%和38.9%,其余11种自身抗体的总阳性率分别为51.5%、24.1%和19.4%,均显著高于健康孕妇(P<0.01)。结果提示:EMT 患者体内存在高水平自身免疫反应,某些自身抗体的增加,可能影响正常生育。     

M3受体肽段免疫大鼠对其肺脏结构和功能的影响

目的 用M3受体合成肽段免疫大鼠建立主动免疫模型,探讨M3受体自身抗体在慢性阻塞性肺疾病发病中的机制.方法 （1）建立免疫组、对照组动物模型共12周.（2）采用SA-ELISA方法检测两组大鼠血清中的M3受体自身抗体.（3）测定大鼠肺功能及动脉血气分析.（4）光镜观察大鼠肺组织病理变化.结果 （1）M3受体自身抗体测定：免疫组阳性率为100%,平均抗体滴度（G）为1∶152,与对照组（阳性率8.33%、抗体滴度1∶24）比较差异有统计学意义（x2=6.68、t=3.15,P＜0.01）.（2）肺功能测定：免疫组吸气阻力明显增高,为（1.77±0.22）cmH2O/ml.sec,与对照组[（1.39±0.21）cmH2O/ml. sec]比较差异有统计学意义,肺动态顺应性及第3秒用力呼气量与用力肺活量比值均降低,分别为（0.33±0.04）ml/cmH2O、（81.57±2.36）%,与对照组[（0.43±0.07）ml/cmH2O、（90.79±0.71）%]比较差异有统计学意义（t=3.1l、2.82、3.23,P＜0.01）.（3）动脉血气测定：免疫组PaO2下降为（52.106±5.269）mmHg,PaCO2上升为（66.248±3.321）mmHg,与对照组[（93.407±3.298）mmHg、（39.125±4.091）mmHg]比较差异均有统计学意义（t=3.86、3.47,P＜0.01）.（4）肺组织病理学检查：对照组大鼠支气管、细支气管黏膜上皮结构完整,肺泡结构正常连续.免疫组大鼠支气管、细支气管黏膜上皮脱落,周围腺体增生伴大量炎性细胞浸润,肺泡结构紊乱,肺间隔增厚,肺泡壁变薄或断裂,肺泡腔扩大,部分融合成肺大泡.（5））M3受体自身抗体滴度与肺功能、动脉血气的相关性：M3受体抗体滴度与肺功能、动脉血气均呈正相关（r=0.84、0.79,P＜0.05）.结论 M3受体抗体可以损害大鼠肺脏的结构和功能,促进COPD的发生、发展.     

Immune Response to Dietary Proteins,Gliadin and Cerebellar Peptides in Children with Autism

Abstract

The mechanisms behind autoimmune reaction to nervous system antigens in autism are not understood. We assessed the reactivity of sera from 50 autism patients and 50 healthy controls to specific peptides from gliadin and the cerebellum. A significant percentage of autism patients showed elevations in antibodies against gliadin and cerebellar peptides simultaneously. For examining cross-reaction between dietary proteins and cerebellar antigens, antibodies were prepared in rabbits, and binding of rabbit anti-gliadin, anti-cerebellar peptides, anti-MBP, anti-milk, anti-egg, anti-soy and anti-corn to either gliadin- or cerebellar-antigen-coated wells was measured. In comparison to anti-gliadin peptide binding to gliadin peptide at 100%, the reaction of anti-cerebellar peptide to gliadin peptide was 22%, whereas the binding of anti-myelin basic protein (MBP), anti-milk, anti-egg and anti-soy to gliadin was less than 10%. Further examination of rabbit anti-gliadin (EQVPLVQQ) and anti-cerebellar (EDVPLLED) 8 amino acid (AA) peptides with human serum albumin (HSA) and an unrelated peptide showed no binding, but the reaction of these antibodies with both the cerebellar and gliadin peptides was greater than 60%. This cross-reaction was further confirmed by DOT-immunoblot and inhibition studies. We conclude that a subgroup of patients with autism produce antibodies against Purkinje cells and gliadin peptides, which may be responsible for some of the neurological symptoms in autism.     

Sperm Antibody Testing in Infertile Men

Six hundred male patients were examined for circulating spermagglutinating antibodies by the Kibrick sperm-agglutination test and 20% demonstrated autoantibodies. The high incidence of positive findings may be explained by the select population studied. Of 80 men tested who demonstrated more than 10% agglutination in their semen, but were otherwise normospermic, 41% demonstrated positive titers by the Kibrick method. Of 300 men examined for circulating sperm-immobilizing antibodies by the Isojima sperm-immobilizing test, 6% had autoantibodies. This high incidence of positive findings demonstrates the need for these tests in males who otherwise appear normospermic or demonstrate an unexplained infertility.     

Pentraxins,Anti-pentraxin Antibodies,and Atherosclerosis

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.     

Spontaneous and induced immunoglobulin synthesis and anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: relation to leukocyte subpopulations in blood and active lesions

Summary Using a reverse plaque forming cell (PFC) assay the production of immunoglobulin (Ig) by peripheral blood mononuclear cells (MNCs) in vitro was studied in 12 patients with Wegener's granulomatosis (WG). Spontaneous IgG production was increased in two of six untreated patients. The IgG response of MNCs from eight untreated patients to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) stimulation was significantly depressed. The IgM and IgA production followed the individual pattern of IgG. Blood B-cell and T-cell subset concentrations were normal before therapy, whereas the monocyte concentration was increased in four of six patients. Titers of anti-neutrophil cytoplasm autoantibodies (ANCAs) did not correlate with spontaneous or induced Ig production nor with blood leukocyte subset concentrations. Biopsy specimens from upper respiratory tract lesions in seven untreated patients showed numerous macrophages, activated T lymphocytes, and plasma cells, suggesting a pathogenetic role of these cells in the development of lesions and local production of ANCAs.     

Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren

Aims/hypothesis. To study temporal changes in positivity for autoantibodies associated with Type I (insulin-dependent) diabetes mellitus and the relations between these antibodies, HLA-DQB1-risk markers and first-phase insulin response (FPIR) in non-diabetic schoolchildren.¶Methods. The stability of the antibody status over 2 years was assessed in 104 schoolchildren initially positive for islet cell antibodies (ICA) or antibodies to the 65 000 M_r isoform of the glutamic acid decarboxylase (GADA) or both and in 104 antibody-negative control children matched for sex, age and place of residence. All children were also studied for their first-phase insulin response and HLA-DQB1 alleles on the second occasion.¶Results. On the second occasion 3 of the 98 initially ICA-positive children, 3/13 of those positive for antibodies to the IA-2 protein (IA-2A), 1/17 GADA-positive and 2/7 of those positive for insulin autoantibodies (IAA) tested negative for these antibodies. Children with IA-2A, GADA, IAA and multiple ( ≥ 2) antibodies had significantly lower first-phase insulin responses than the control children. In contrast, these responses did not differ between subjects with and without specific HLA-DQB1-risk alleles or genotypes. Of the six subjects with a considerably reduced first-phase insulin response three had multiple antibodies on both occasions but none of them had a DQB1 genotype conferring increased diabetes risk. Two subjects progressed to Type I diabetes within 3.4 years of follow-up, both of them having multiple antibodies and a considerably reduced first-phase insulin response but neither of them having a DQB1-risk genotype.¶Conclusions/interpretation. Positivity for diabetes-associated autoantibodies is a relatively stable phenomenon in unaffected schoolchildren, although conversion to seronegativity can occur occasionally. Our observations also indicate that DQB1 alleles associated with decreased susceptibility to Type I diabetes do not protect from impaired beta-cell function or from progression to overt disease in initially unaffected schoolchildren. [Diabetologia (2000) 43: 457–464]     

A Monoclonal Antibody-Based Characterization of Autoantibodies against Glutamic Acid Decarboxylase in Adults with Latent Autoimmune Diabetes

Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type 1) diabetes. However, these autoantibodies are also found in patients with Stiff-man syndrome (SMS) without onset of diabetes and some diabetic patients who initially present as non-insulin dependent (Type 11) diabetes later becoming insulin-dependent, called as latent autoimmune diabetes in adults (LADA). To study the immune response to GAD in these LADA patients a competitive radiobinding assay based on murine monoclonal antibodies recognizing three different GAD regions was performed. The monoclonal antibodies against GAD recognize two different linear epitopes localized at the N- (amino acids 4-17) and C-terminus (amino acids 572-585) and one conformation-dependent epitope region (amino acids 221-442 IDDM-El) known to be immunodominant for diabetes-associated autoantibodies. All LADA sera (20/20) reduced substantially the ¹²⁵I-GAD binding of the monoclonal antibodies reactive with the conformation-dependent epitope region IDDM-El and only 20% of these sera additionally diminished the ¹²⁵I-GAD65 binding by those monoclonals reactive with the both linear epitopes. The SMS sera completely abolished the GAD binding of all three monoclonals, reflecting a broader repertoire including an immune response against the IDDM-El, a conformation-dependent GAD65 epitope region, also revealed if the SMS sera are diluted to equivalent antibody concentrations. In summary, our results show that diabetes-associated GAD autoantibodies even in adult patients with a late autoimmune process preferentially recognize a conformation-dependent middle GAD65 region. An immune response to all three GAD epitope regions is seldom in these LADA patients and only detectable in association with high antibody titres.     

The Prevalence of Anti-acetylcholinesterase Antibodies in Autoimmune Disease

A robust and precise enzyme linked immunosorbent assay (ELISA) with proven sensitivity and specificity has been employed to detect human antibodies (allogenic/autogenic) to human acetylcholinesterase (AChE). The sensitivity of the method has been established using mouse monoclonal antibodies (0.8?ng/ml) and uniquely, human sera positive for anti-Yt^a allogenic antibodies, to one phenotypic form (most common) of human AChE. The latter was also used as the positive human control to ensure functionality of the assay. The ELISA method was used to establish a normal distribution curve for absorbance values employing sera from healthy blood donors Subsequently, the ELISA was employed to investigate the prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease and patients with non-autoimmune thyroid disease (diseased control). The results indicate that there is not a high prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease. The lack of anti-AChE autoantibodies in patients' with clinically apparent Graves' ophthalmopathy, mitigates against there being a causal role of such antibodies in Graves' associated eye disease.