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Histidine Decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
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2003 In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, Vol. 88, no 4, 1445-1452 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 88, no 4, 1445-1452 p.
URN: urn:nbn:se:uu:diva-90402OAI: oai:DiVA.org:uu-90402DiVA: diva2:162743
Available from: 2003-04-29 Created: 2003-04-29Bibliographically approved
In thesis
1. Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
Open this publication in new window or tab >>Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 44 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1256
Medicine, autoantibodies, autoimmune polyendocrine syndrome type 1, cysteine sulfinic acid decarboxylase, histidine decarboxylase, systemic lupus erythematosus, ahnak, CLLD4, Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Molecular Medicine
urn:nbn:se:uu:diva-3421 (URN)91-554-5618-9 (ISBN)
Public defence
2003-05-22, Rosénsalen, Akademiska sjukhuset (Ingång 95/96), Uppsala, 13:15 (English)
Available from: 2003-04-29 Created: 2003-04-29 Last updated: 2010-01-14Bibliographically approved

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