The concept of autoimmune pancreatitis and its immunological backgrounds

The aim of the present review is to describe the epidemiological and clinical aspects of autoimmune pancreatitis (AIP), and to report the data existing in the English literature on the usefulness of IgG4 serum levels, as well as of other serological markers in the diagnosis and follow-up of patients with AIP. The serum IgG4 subclass seems to be a good marker of AIP, and its determination should be included in the diagnostic work-up of this disease. The relationship between allergy and IgG4 serum concentrations in patients with AIP has also been reviewed. Finally, we have revised the current literature data on the imaging feature of AIP and the therapeutic modalities for curing AIP patients.     

Inter‐Test Comparison Between Filter Paper Absorbed Blood Eluate and Serum for Malaria Serology by Enzyme Immunoassay: An Operational Feasibility

Abstract

Antimalarial IgG and IgM were detected by enzyme immunoassay in finger‐stick blood samples collected in capillary tubes and also spotted onto Whatman filter paper. Assay was performed in 92 blood samples obtained from 53 falciparum malaria patients, representing 23 fever cases (malaria negative) and 16 healthy individuals. A simple indirect ELISA was done using Plasmodium falciparum lysate and MSP1₁₉ peptide as antigens. Total IgG and IgM contents were also estimated in individual sera and filter paper eluate by single radial immunodiffusion (SRID). Assay results of both serum and filter paper eluates were compared. The sensitivity and specificity of the assays for IgG measurement were comparable between serum and filter paper eluates (P < 0.001), whereas, in case of IgM, detection level was poor in filter paper eluates as observed by ELISA and SRID. The filter paper eluates may serve the purpose of antigen‐specific IgG detection in seroepidemiological surveys.     

IgG4相关性疾病20例临床特征分析

目的 总结IgG4相关性疾病临床特征及预后,提高认识,做到早期诊断及合理治疗.方法 对在我院住院明确诊断的20例IgG4相关性疾病患者资料进行回顾性分析.结果 20例患者中男性14例,女性6例,平均年龄58岁,胰腺和胆管为最常见受累器官,17例患者(85％)有≥2个器官受累.所有患者血清IgG4均明显升高(＞1350 mg/L).12例患者行组织病理学检查,主要表现为组织弥漫性纤维化,伴有大量淋巴细胞、浆细胞浸润,免疫组织化学可见CD38阳性浆细胞浸润,IgG4阳性浆细胞浸润,IgG4阳性浆细胞占IgG阳性浆细胞比例均＞40％.20例患者中,除1例患者死于急性化脓性胆管炎及1例未治疗,其余患者病情均明显缓解.结论 IgG4相关性疾病临床症状无特异性,血清IgG4可作为疑似病例的首选检查方法,及时应用糖皮质激素可迅速缓解病情.     

MMP-3、IgG和CD68在青少年与中老年突出腰椎间盘组织中的表达分析

【摘要】 目的：比较细胞因子基质金属蛋白酶3（matrix metalloproteinases 3,MMP-3）、IgG和CD68在青少年与中老年患者突出腰椎间盘组织中的表达,探讨两个年龄段腰椎间盘突出的病因。方法：收集40例腰椎间盘突出症患者的突出腰椎间盘髓核标本,青少年组18例,年龄11～25岁,平均20.6±3.4岁;中老年组22例,年龄40～72岁,平均48.0±10.3岁。HE染色观察标本退变情况,免疫组化染色检测MMP-3、IgG和CD68的表达,光学显微镜下观测并计录数据。结果：标本HE染色提示多数（17/22）中老年组腰椎间盘存在明显退变,青少年组多数椎间盘（13/18）退变不明显或无退变。MMP-3阳性率青少年组（33.33%）低于中老年组（81.82%）;IgG阳性率青少年组（66.67%）高于中老年组（31.82%）;CD-68阳性率青少年组（83.33%）高于中老年组（45.45%）,两组MMP-3、IgG和CD68的表达阳性率比较,差异均有统计学意义（P<0.05）。结论：免疫和炎症反应可能是青少年腰椎间盘突出的重要病因,而中老年腰椎间盘突出可能主要与退变有关。     

“Plasma Cell Hepatitis” in Liver Allografts: Identification and Characterization of an IgG4‐Rich Cohort

Plasma cell hepatitis (PCH), also known as “de novo autoimmune” hepatitis, is an increasingly recognized, but suboptimally named and poorly understood, category of late allograft dysfunction strongly resembling autoimmune hepatitis (AIH): They share plasma‐cell‐rich necro‐inflammatory activity on biopsy, autoantibodies and steroid responsiveness, but overlap with rejection is problematic. A retrospective study of clinical, serological, histopathological and IgG4 immunohistological features of PCH (n = 20) in liver allograft recipients, native liver AIH (n = 19) and plasma‐cell‐rich renal allograft rejection (n = 20) showed: (1) high frequency (44%) of HLA‐DR15; (2) less female predominance (p = 0.03) and (3) n = 9/20 PCH recipients showed >25 IgG4+ plasma cells/high‐power field (IgG4+ PCH) versus AIH (n = 1/19, p = 0.008) or plasma‐cell‐rich kidney rejection (n = 2/20, p = 0.03). The IgG4+ PCH (n = 9) subgroup showed lower alanine transaminase (ALT) (p < 0.01) and aspartate transaminase (AST) (p < 0.05) at index biopsy but (a) higher plasma cell number/percentage, (b) more aggressive‐appearing portal/periportal and perivenular necro‐inflammatory activity and (c) more severe portal/periportal fibrosis than IgG4? PCH (n = 11). Significant demographic, histopathologic and plasma cell phenotype differences between PCH and AIH suggest distinct pathogenic mechanisms for at least the IgG4+ PCH subgroup likely representing an overlap between allo‐ and auto‐immunity. IgG4+ PCH was associated with fibrosis, but also highly responsive to increased immunosuppression.

     

IgG subclass profile among anti‐Glutathione S‐transferase T1 antibodies in post‐transplant de novo immune hepatitis

Although the pathogenic pathways leading to de novo immune hepatitis (IH) are not completely understood, we have shown strong evidences of an antidonor response against Glutathione S‐transferase T1 (GSTT1), an antigen exclusively expressed in the donor liver. The first sign of this process is the production of GSTT1 antibodies that, in 25% of the cases, will precede de novo IH. Because the presence of the antibodies is not sufficient to trigger the disease, we aimed to study GSTT1 IgG subclasses in a group of 18 liver transplant patients, 12 that developed de novo IH and 6 that remained free of disease. Surprisingly, the predominant subclasses were IgG1‐_GSTT1 and IgG4‐_GSTT1. The presence of IgG4‐expressing plasma cells was also investigated in 10 available liver biopsies. Six biopsies coinciding with diagnosis showed a mean value of 32.8 IgG4+ plasma cells/hpf vs. 5.55 in patients without the disease. We have not found a distinctive GSTT1‐IgG profile in patients with de novo IH, but the ratio IgG1‐_GSTT1/IgG4‐_GSTT1 in samples from close to the time of diagnosis seemed to be important. The novel finding of abundant IgG4‐_GSTT1 in liver transplantation is intriguing, but their possible role in pathogenesis of de novo IH remains unknown.     

Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter,open label clinical trial

Background

To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial.