原发性胆汁性肝硬化谱系中的体液自身免疫反应异质性
Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis.
作者信息
Dellavance Alessandra, Cançado Eduardo Luiz R, Abrantes-Lemos Clarice Pires, Harriz Michelle, Marvulle Valdecir, Andrade Luis Eduardo C
机构信息
Rheumatology Division, Universidade Federal de São Paulo, UNIFESP, Rua Botucatu 740, São Paulo, SP 04023-900 Brazil ; Research and Development Division, Fleury Medicine and Health Laboratories, São Paulo, Brazil.
出版信息
Hepatol Int. 2012 Dec 5;7(2):775-84. doi: 10.1007/s12072-012-9413-0. Print 2013 Jun.
OBJECTIVE
To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease.
METHODS
A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA.
RESULTS
High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).
CONCLUSION
The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.
目的
比较原发性胆汁性肝硬化（PBC）患者与抗线粒体抗体（AMA）阳性但无疾病临床或生化证据个体的自身抗体特征。
方法
将212份AMA阳性血清样本分为四组：PBC（确诊PBC，n = 93）；PBC/自身免疫性疾病（AID；PBC合并其他AID，n = 37）；生化正常（BN）个体（n = 61）；以及BN/AID（BN合并其他AID，n = 21）。通过大鼠肾间接免疫荧光法（IIF）检测样本（IIF-AMA），并采用酶联免疫吸附测定法检测[抗丙酮酸脱氢酶E2复合物（PDC-E2）、gp-210、Sp-100和CENP-A/B抗体]。通过IIF-AMA测定AMA同种型。采用8M尿素修饰的酶联免疫吸附测定法测定抗PDC-E2 IgG的亲和力。
结果
高滴度IIF-AMA在PBC和PBC/AID中更常见（分别为57%和70%），而在BN和BN/AID样本中较少见（分别为23%和19%）（p < 0.001）。三联同种型IIF-AMA（IgA/IgM/IgG）在PBC和PBC/AID样本中更常见（分别为35%和43%），而在BN样本中较少见（18%；p = 0.008；p = 0.013）。PBC（平均3.82；95%可信区间3.36 - 4.29）和PBC/AID样本（3.89；3.15 - 4.63）中的抗PDC-E2水平高于BN（2.43；1.92 - 2.94）和BN/AID样本（2.52；1.54 - 3.50）（p < 0.oo1）。PBC（平均64.5%；95%可信区间57.5 - 71.5%）和PBC/AID样本（66.1%；54.4 - 77.8%）中的抗PDC-E2亲和力高于BN样本（39.2%；30.9 - 37.5%）（p < 0.001）。与BN（p = 0.008）和BN/AID样本（p = 0.002）相比，PBC和PBC/AID识别更多细胞结构域（线粒体、核膜、PML/sp-100小体、着丝粒）。三个变量与确诊PBC独立相关：高亲和力抗PDC-E2（比值比4.121；95%可信区间2.118 - 8.019）；高滴度IIF-AMA（比值比4.890；2.319 - 10.314）；抗三种或更多抗原性细胞结构域的抗体（比值比9.414；1.924 - 46.060）。
结论
与AMA阳性的生化正常个体相比，确诊PBC的自身抗体谱在数量和质量上更显著。
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