ALPHA-SUBUNIT AND BETA-SUBUNIT OF THE GASTRIC H+/K+-ATPASE ARE CONCORDANTLY TARGETED BY PARIETAL-CELL AUTOANTIBODIES ASSOCIATED WITH AUTOIMMUNE GASTRITIS

被引：48

作者：

CALLAGHAN, JM ^{[1
]}

KHAN, MA ^{[1
]}

ALDERUCCIO, F ^{[1
]}

VANDRIEL, IR ^{[1
]}

GLEESON, PA ^{[1
]}

TOH, BH ^{[1
]}

机构：

[1] MONASH UNIV,SCH MED,DEPT PATHOL & IMMUNOL,MELBOURNE,VIC 3181,AUSTRALIA

来源：

AUTOIMMUNITY | 1993年 / 16卷 / 04期

基金：

英国医学研究理事会;

关键词：

AUTOIMMUNITY; H+/K+-ATPASE; AUTOIMMUNE; GASTRITIS;

D O I：

10.3109/08916939309014648

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We have previously shown that parietal cell autoantibodies predominantly react with a 60-90 kDa gastric autoantigen(1,2), subsequently identified as the beta subunit of the gastric H+/K+-ATPase (EC 3.6.1.3) (proton pump)(3-5) whereas Karlsson et al(6) showed that these autoantibodies primarily target the 95 kDa a subunit of the pump. In view of these discordant results, we have reassessed the reactivity of parietal cell autoantibodies with the two subunits of the gastric H+/K+-ATPase. We show here that all 26 parietal cell autoantibody-positive sera immunoblot both subunits under appropriate, but mutually exclusive, conditions. Thus, reactivity of anti- parietal cell autoantibodies with the 95 kDa alpha subunit is optimal when the SDS-PAGE is carried out with samples which are reduced but not boiled. Whereas reactivity with the 60-90 kDa beta subunit is optimal with samples which are boiled but not reduced. Autoantibody reactivity with the beta subunit is critically dependent on the presence of a full complement of N-linked glycans since partially deglycosylated protein, and recombinant beta subunit expressed in COS cells, bearing high mannose N-glycans, failed to bind to the autoantibody. These studies also suggest that B cell auto-epitopes are located on the lumenal domain of the beta subunit. Reactivity of parietal cell autoantibodies with a bacterial fusion protein incorporating the catalytic cytoplasmic domain of the a subunit suggests the presence of auto-epitopes in this region of the molecule.

引用

页码：289 / 295

页数：7

共 15 条

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