IgA肾病患者血清aIgA1对系膜细胞增殖的影响

目的观察IgA肾病（IgAN）患者与正常人的血清热聚合IgA1（aIgA1）对系膜细胞（MC）增殖的影响。方法收集原发性IgAN患者及健康人的血清标本,利用Jacalin-agarose亲和层析联合Sephacryl S-200HR分子筛层析法分离获得血清单体IgA1（mIgA1）,将mIgA1热聚合为aIgA1。利用患者及正常人的aIgA1分别刺激小鼠MSC-1097系膜细胞株,利用MTT法检测aIgA1对系膜细胞增殖的影响。结果aIgA1刺激48h组的吸光度是24h组的1.59倍（P=0.000）。不同浓度aIgA1刺激组间MTT吸光度的差异有统计学意义（P=0.000）,相比于阴性对照组（SFM）,0.25mg/mL组、0.5mg/mL组、1mg/mL组的吸光度分别为SFM的1.67、1.74、1.77倍（P=0.000）;2mg/mL组的吸光度是SFM的1.15倍（P=0.086）。在刺激24h时患者0.25mg/mL组的aIgA1就可促进系膜细胞增殖了,其吸光度是SFM的1.34倍（P〈0.05）,而正常对照组则要在浓度达到1mg/mL时才引起系膜细胞增殖,其吸光度为SFM的1.33倍（P〈0.05）。结论研究结果提示患者及正常人的aIgA1均可促进系膜细胞增殖,这种增殖表现为时间依赖性及一定的剂量依赖性,在高浓度时aIgA1促系膜细胞增殖的作用消失了;患者的aIgA1可能更易与系膜细胞结合,刺激相同时间时患者低浓度aIgA1既可引起MC增殖。     

前必治口服液治疗慢性前列腺炎45例临床观察

应用纯中药制剂前必治口服液治疗慢性前列腺炎４５例，并测定了治疗前后患者前列腺的局部免疫功能（ＥＰＳ－ＩｇＡ、ＩｇＧ含量）、前列腺液中微量元素锌（ＥＰＳ－Ｚｎ）的含量。结果表明，前必治能明显改善慢性细菌性或无菌性前列腺炎患者的临床症状，并能显著提高其ＥＰＳ－ＩｇＡ、ＩｇＧ和ＥＰＳ－Ｚｎ水平，提示前必治具有良好的抗炎、抗力作用，并能改善前列腺的局部免疫功能和Ｚｎ含量水平，这可能是前必治口服液治疗慢性前列腺炎的作用机理之一。     

Proteomic analysis of excretory/secretory products released by Teladorsagia circumcincta larvae early post-infection

Teladorsagia circumcincta is an important parasitic nematode of domestic small ruminants. Drug resistance in this species is common so alternative methods of control are required. As animals develop immunity to T. circumcincta, vaccination is a valid option. Little is known about the antigens that play a role in stimulating immunity at this host/parasite interface. As responses generated between 1 and 5 dpi are known to affect development of these nematodes in their gastric niche, we focused on proteins released during the early stages of infection. To identify molecules potentially involved in immunity, we undertook a proteomics analysis of proteins released from larvae harvested at 1-, 3- and 5-days post-infection (dpi). This analysis produced peptide sequence data that was used to search information available in T. circumcincta expressed sequence tag (EST) databases and enabled identification of a number of excretory/secretory (ES) proteins. Immunoblots were performed to assess the relative molecular weight of ES antigens that were targets of local IgA responses in mucus from sheep rendered immune to infection. ELISA was performed to assess antigen-specific mucus IgA levels in individual sheep. These experiments provided preliminary evidence that the proteins identified in the larval secretome were subject to these antibody responses.     

The outcome of patients with unclassified hypogammaglobulinemia in early childhood

Symptomatic hypogammaglobulinemia in childhood may be the initial finding of primary immunodeficiency (PID) or may be due to delay in maturation of immunoglobulin synthesis. The aim of this study was to review the clinical and laboratory records of patients with unclassified hypogammaglobulinemia and to evaluate whether these children experience changes in serum immunoglobulin concentrations during long‐term followup and have an exact diagnosis in natural course of disease. We reviewed the data of 412 patients who were diagnosed as PID with symptomatic hypogammaglobulinemia. Thirty‐seven patients with hypogammaglobulinemia [19 males (51.4%) and 18 females (48.6%), with a followup of 34.1 ± 22.0 months] who were not classified according to European Society for Immunodeficiencies diagnostic criteria were included in this study. The mean age at the beginning of the symptoms was 21.4 ± 20.6 months and the mean age at admission was 51.5 ± 25.8 months. The commonest clinical presentations were recurrent upper (94.6%) and/or lower (40.5%) respiratory infections, urinary infection (27%) and gastroenteritis (10.8%). Percentage of consanguinity was 8%. Of the initial 37 patients, 18 (48.6%) spontaneously corrected their immunoglobulin abnormalities during followup. Clinical symptoms of these patients were also improved. IgG, IgA and IgM levels reached to normal levels at ages 62.5 ± 21.8, 72.0 ± 11.2, 55.2 ± 7.8 months, respectively. In remaining 19 patients with undefined/unclassified hypogammaglobulinemia, three partial IgA deficiency, seven IgG subclass deficiency, two selective IgM deficiency and two common variable immunodeficiency (CVID) were diagnosed by long‐term monitoring of immunoglobulin levels. Five (13.5%) of the 37 unclassified patients could not be exactly diagnosed while two of them might have a T‐cell defect and three of them still had low IgG and IgA levels but adequate antibody responses against vaccine antigens. In conclusion, it is important to monitor symptomatic patients with hypogammaglobulinemia periodically. Some children may spontaneously correct their immunoglobulin abnormalities not in the first 30 months of age, but during the first decade of life and some of them may have a severe PID like CVID.     

益气增免冲剂防治儿童反复呼吸道感染疗效观察和机制探讨

目的观察益气增免冲剂防治儿童反复呼吸道感染的疗效,探讨其作用机制。方法共纳入123例复感儿,随机数字表法分为研究组和对照组。对照组采用诱因预防(一级预防)和急性感染期西药常规治疗(二级治疗),研究组同时加服自拟益气增免冲剂。疗程3月,随访1年,观察急性感染发作频次、每次持续时间和感染部位,测量治疗前、治疗后、治疗后3月、治疗后6月4个时间点的IgG、IgA水平,对符合方案集患儿采用Mann-Whitney U检验和重复测量设计方差分析进行统计学处理。结果研究组显效、有效和无效率分别是58.93%、37.50%和3.57%,对照组分别为32.20%、49.15%和18.64%(z=-3.255,P=0.001);两组4个时点的IgG、IgA水平差异有高度统计意义(P=0.000),研究组高于对照组(P=0.000),其趋势变化不平行(P=0.000)。结论益气增免冲剂能减少复感儿呼吸道感染频次,缩短急性期病程,其机理可能是通过调节机体IgG、IgA水平实现的。     

No evidence for a role of cosmc-chaperone mutations in European IgA nephropathy patients

Background. Altered IgA1 galactosylation is involved in thepathogenesis of IgA nephropathy (IgAN). The galactosyltransferasecore-1 beta3-galactosyltransferase-1 (C1GALT1) and its chaperonecosmc are specifically required for O-galactosylation of theIgA1 hinge region. Mutations in the cosmc gene result in a secondaryloss of function of C1GALT1 with subsequent undergalactosylationof glycoproteins. Mosaic mutations of cosmc have been shownto result in autoimmune disease. We hypothesized that cosmcmutations might contribute to the altered IgA1 galactosylationin IgAN patients. Methods. We studied cosmc gene sequences in genomic DNA obtainedfrom male patients with biopsy-proven sporadic (n = 33) andfamilial IgAN (n = 6 patients from different families). To accountfor a potential mosaicism we sequenced cosmc in 10 differentperipheral blood mononuclear cell DNA clones of every patient.To specifically assess potential mosaic mutations in IgA-producingcells, cosmc mutations were also analysed in DNA isolated fromCD20+ B-lymphocytes from three male IgAN patients. Results. Despite our extensive genomic analysis, the data revealedno functionally relevant cosmc gene variants in sporadic orfamilial IgAN cases. A cosmc gene polymorphism, rs17261572,was identified in these IgAN patients in a similar frequencyas previously reported in healthy adults. A functional consequenceof this polymorphism has not yet been determined. Conclusion. Although decreased C1GALT1 activity has been implicatedin the IgAN pathogenesis and cosmc chaperone mutations can causeautoimmune disease, our data provide no evidence for a relevantrole of cosmc gene mutations in European patients with sporadicor familial IgAN.     

Prospective analysis of the incidence of autoimmune bullous disorders in Lower Franconia,Germany

Background: Only limited epidemiologic data are available on autoimmune bullous diseases. Improved diagnostic tools should have led to an increased incidence. To test this hypothesis, all patients with autoimmune bullous disorders who were treated in the Department of Dermatology at the University of Würzburg, Germany, between January 2001 and June 2002 were analysed prospectively. Patients and Methods: Epidemiologic data of patients diagnosed with an autoimmune bullous disease during this time period were registered and statistically evaluated. Diagnosis was based on the clinical picture and specific immunopathological findings. Only patients from Lower Franconia, a well‐defined administrative region of Southern Germany, were included into this study. Results: During the study period, 41 patients with an autoimmune bullous disease were diagnosed, including 27 with bullous pemphigoid, 4 with pemphigoid gestationis and mucous membrane pemphigoid, 2 with dermatitis herpetiformis and linear IgA disease, and 1 with epidermolysis bullosa acquisita and pemphigus vulgaris, respectively. The highest incidence was calculated for bullous pemphigoid (13.4 per 1 million inhabitants per year) followed by pemphigoid gestationis (2.0) and mucous membrane pemphigoid (2.0). Patients with mucous membrane pemphigoid were found to have the highest mean age at disease onset (76 years) followed by patients with bullous pemphigoid (74 years). Conclusions: This is the first prospective study on the incidence of autoimmune bullous disorders. Subepidermal blistering autoimmune diseases were shown to be more frequent than previously reported for Central Europe. This is most likely due to improved diagnostic tools for and increased awareness of these diseases.