Liver abnormalities in connective tissue diseases

The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd–Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.     

In angioimmunoblastic T-cell lymphoma,neoplastic T cells may be a minor cell population. A molecular single-cell and immunohistochemical study

The significance of T-cell proliferations in angioimmunoblastic lymphoma (AILD) is still enigmatic. Although classified as a malignant T-cell lymphoma in the World Health Organisation lymphoma classification, some cases of AILD lack dominant T-cell clones. In a previous study, based on single-cell polymerase chain reaction (PCR), we obtained similar results as studies of AILD using Southern blot or conventional PCR: some cases of AILD contained large T-cell clones, and, in other cases, T-cell clones were undetectable. As in single-cell studies, only a limited number of cells could be investigated; thus, we wanted to gain more insight into the amount and distribution of tumour cells. By applying triple immunofluorescent staining with antibodies directed against T-cell receptor V-family-specific epitopes, we investigated T-cell populations in AILD and their localisation in the tissue in relation to B cells (CD20) and follicular dendritic cells (CD21). In two of five cases investigated, only a minority of the T-cells compartment belonged to the tumour clone. Neoplastic T cells were found throughout the tissue, including areas dominated by B cells.     

血管免疫母细胞淋巴结病23例临床分析

目的通过对血管免疫母细胞淋巴结病(AILD)临床表现的分析,为AILD的诊断和治疗提供依据.方法回顾性分析近15年收治的23例AILD住院患者的各项临床资料.结果 AILD临床表现多样,可累及多脏器;确诊需淋巴结活检,而反应性淋巴结增生与AILD关系密切;此病预后差,积极治疗可延长生存期.结论临床考虑AILD时,多次淋巴结活检是必要的.治疗上宜采用联合化疗并加α-干扰素.     

Multicentric angiofollicular lymph node hyperplasia and associated carcinoma

There is a well described association between multicentric angiofollicular hyperplasia and non-Hodgkin's lymphoma and/or Kaposi's sarcoma. Two cases of multifocal angiofollicular hyperplasia and associated carcinomas and non-Hodgkin's lymphoma are reported. We suggest that underlying immunological defects in patients with multicentric angiofollicular hyperplasia make them susceptible to the development of carcinomas, as well as non-Hodgkin's lymphoma and Kaposi's sarcoma. © 1994 Wiley-Liss, Inc.     

Angioimmunoblastic T-cell lymphoma with autoimmune thrombocytopenia: A report of two cases

We report two patients, a 68-year-old man (Case 1) and a 66-year-old man (Case 2), with polyclonal gammopathy, lymphadenopathy, thrombocytopenia, and high platelet-associated IgG (PAIgG) level. We initially diagnosed them as having angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). From confirmation of clear cells by careful observation and detection of rearrangement bands of T cell receptors by Southern blot hybridization analysis, we finally concluded that their diagnoses were compatible with angioimmunoblastic T-cell lymphoma (AILT). AILT with autoimmune thrombocytopenia (AIT) is very rare, and all the reported cases were Japanese ones.     

自身免疫性抗体检测在临床诊断自身免疫性肝病中的价值评估

目的探讨自身免疫抗体检测在临床诊断自身免疫性肝病(AILD)中的价值。方法选取AILD患者69例、病毒性肝炎患者77例以及正常健康者65例,检测并比较三组的血清自身免疫抗体和肝功能指标。结果AILD组的血清自身免疫抗体ANA、AMA-M2、LKM-1、SP100、SLA阳性率以及总阳性率均显著高于病毒性肝炎组和健康对照组(P<0.05)。AILD组的肝功能指标(ALT、AST、GGT、ALP)含量均显著高于病毒性肝炎组和健康对照组(P<0.05)。结论自身免疫抗体检测对临床诊断自身免疫性肝病具有重要的应用价值,可用于自身免疫性肝病的早期诊断,联合肝功能指标检测有利于提高诊断准确性。     

IL-17 and IL-17-producing cells and liver diseases,with focus on autoimmune liver diseases

The pro-inflammatory cytokine interleukin(IL)-17 and IL-17-producing cells are important players in the pathogenesis of many autoimmune / inflammatory diseases. More recently, they have been associated with liver diseases. This review first describes the general knowledge on IL-17 and IL-17 producing cells. The second part describes the in vitro and in vivo effects of IL-17 on liver cells and the contribution of IL-17 producing cells to liver diseases. IL-17 induces immune cell infiltration and liver damage driving to hepatic inflammation and fibrosis and contributes to autoimmune liver diseases. The circulating levels of IL-17 and the frequency of IL-17-producing cells are elevated in a variety of acute and chronic liver diseases. The last part focuses on the effects of IL-17 deletion or neutralization in various murine models. Some of these observed beneficial effects suggest that targeting the IL-17 axis could be a new therapeutic strategy to prevent chronicity and progression of various liver diseases.     

The role of 2-chlorodeoxyadenosine in the treatment of patients with refractory angioimmunoblastic lymphadenopathy with dysproteinemia

Treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) often constitutes a challenge for the clinical haematologist. Single-agent and combination chemotherapy have failed to increase the response rate or survival of patients with AILD. A total of seven patients with refractory or relapsed AILD were treated with 2-chlorodeoxyadenosine (2-CdA) for variable number of cycles. The overall response rate was 57% with two patients (28.5%) achieving complete and sustained response. 2-Chlorodeoxyadenosine appears to be an active agent for patients with previously treated AILD. Phase II studies evaluating the efficacy of this agent as front-line treatment for AILD are justified, especially in the absence of any effective therapy for this disorder.