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Epitopes of calreticulin recognised by IgA autoantibodies from patients with hepatic and coeliac disease.
Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2003-11-20 , DOI: 10.1016/s0896-8411(03)00137-9
Daniel Sánchez 1 , Ludmila Tucková , Thomas Mothes , Wolfgang Kreisel , Zdenek Benes , Helena Tlaskalová-Hogenová
Affiliation  

Calreticulin (CRT) was identified as a frequent target of serum autoantibodies (Ab) in various diseases, but anti-CRT Ab of IgA isotype were described only in coeliac (CLD) and some hepatic diseases. Employing ELISA with recombinant CRT we found significantly higher (P<0.001) levels of IgA anti-CRT Ab in sera of patients with primary biliary cirrhosis (PBC) (77.6+/-8.9 AU/mean+/-SE), autoimmune hepatitis (AIH) (105.1+/-9.2 AU) and alcoholic liver cirrhosis (ALC) (193.5+/-21.0 AU) relative to healthy controls (38.6+/-2.0 AU). The levels of IgG anti-CRT Ab in sera of patients with PBC (59.5+/-3.4 AU), AIH (89.7+/-7.9 AU) and ALC (86.4+/-6.2 AU) were also significantly increased (P<0.001) when compared with controls (38.5+/-2.1 AU). Pepscan technique with decapeptides of CRT (each overlapping by eight amino acids) revealed antigenic epitopes of this molecule recognised by IgA Ab of almost all tested patients-KGKNVLINKD and QVKSGTIFDNFL. We also identified disease specific antigenic epitopes on CRT molecule, predominantly recognised by IgA Ab of patients suffering from a particular disease: GGYVKLFPNS and YVKLFPNSLD in AIH (83%, 92% of patients), GLQTSQDARF and EQRLKEEEED in CLD (both 75%) and ASKPEDWDER in ALC (67%). Identification of disease specific CRT epitopes contributes to clarification of autoreactivity against this molecule.

中文翻译:

肝和腹腔疾病患者的IgA自身抗体识别的钙网蛋白表位。

钙网蛋白(CRT)被确定为多种疾病中血清自身抗体(Ab)的常见靶标,但仅在腹腔(CLD)和某些肝脏疾病中描述了IgA同种型的抗CRT Ab。使用重组CRT的ELISA我们发现原发性胆汁性肝硬化(PBC)(77.6 +/- 8.9 AU /平均值+/- SE),自身免疫性肝炎(AIH)患者的血清中IgA抗CRT Ab的水平显着更高(P <0.001) )(105.1 +/- 9.2 AU)和酒精性肝硬化(ALC)(193.5 +/- 21.0 AU)相对于健康对照组(38.6 +/- 2.0 AU)。PBC(59.5 +/- 3.4 AU),AIH(89.7 +/- 7.9 AU)和ALC(86.4 +/- 6.2 AU)患者血清中的IgG抗CRT Ab水平也显着升高(P <0.001 )与对照(38.5 +/- 2.1 AU)相比。带有CRT十肽的Pepscan技术(每个肽都重叠八个氨基酸)揭示了该分子的抗原表位,几乎所有受测患者KGKNVLINKD和QVKSGTIFDNFL被IgA Ab识别。我们还确定了CRT分子上特定于疾病的抗原表位,主要由患有特定疾病的患者的IgA Ab识别:AIH中的GGYVKLFPNS和YVKLFPNSLD(83%,患者的92%),CLD中的GLQTSQDARF和EQRLKEEEED(均为75%)和ALC中的ASKPEDWDER(67%)。疾病特异性CRT表位的鉴定有助于阐明对该分子的自身反应性。IgA Ab主要识别患有特定疾病的患者:AIH中的GGYVKLFPNS和YVKLFPNSLD(83%,占92%),CLD中的GLQTSQDARF和EQRLKEEEED(均为75%)和ALC中的ASKPEDWDER(占67%)。疾病特异性CRT表位的鉴定有助于阐明对该分子的自身反应性。IgA Ab主要识别患有特定疾病的患者:AIH中的GGYVKLFPNS和YVKLFPNSLD(83%,占92%),CLD中的GLQTSQDARF和EQRLKEEEED(均为75%)和ALC中的ASKPEDWDER(占67%)。疾病特异性CRT表位的鉴定有助于阐明对该分子的自身反应性。
更新日期:2019-11-01
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