Identification of an autoimmune enteropathy-related 75-kilodalton antigen

Background & Aims: We have previously reported a 75-kilodalton autoantigen specific to X-linked autoimmune enteropathy (AIE) associated with tubulone- phropathy. The aim of this study was to identify the autoantigen. Methods: Complementary DNA (cDNA) clones were isolated by immunoscreening a human du odenal cDNA-expression library with serum from a patient with AIE. Results: cDNA encoding the 75-kilodalton antigen (AIE-75) was identified. The compo site nucleotide sequence of the cDNA for AIE-75 was 2214 base pairs long an d encoded 552 amino acids, The genomic sequence of AIE-75 was found in Sequ ence DataBank, which consisted of 21 exons and was located on the chromosom e 11p14.3. Recombinant AIE-75 specifically reacted with sera from 3 of 4 un related patients with AIE but not with 58 control sera. AIE-75 was predomin antly distributed in the epithelial cells of the luminal surface and the up per half of the crypts of the intestine and in the proximal renal tubulus. Similarity searches revealed that the AIE-75 cDNA sequence was an authentic form of several colon cancer-related cDNAs of unknown function. The deduce d amino acid sequence contained 3 conserved PSD-95/Dlg/ZO-1 (PDZ) domains. Conclusions: AIE-75 is a PDZ domain-containing protein expressed in the dif ferentiated epithelial cells of the intestine and kidney and may be involve d in protein-protein interaction, The identification of the autoantigen may prove useful in the approach to the pathogenesis of this poorly understood disease.