Abstract
There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as determined by immunoblotting. We have now identified one of the major autoantibody specificities using expression cloning. Serum from a BD patient was used as a probe to immunoscreen a λZAP expression cDNA library. Candidate autoantigen cDNAs were characterized by direct nucleotide sequencing and their expressed products were examined for reactivity to the entire panel of BD sera using immunoprecipitation. Reactivity was also examined with normal control sera and disease control sera from patients with lupus and Sjögren's syndrome. Six independent candidate clones were isolated from the cDNA library screen and were identified as overlapping partial human kinectin cDNAs. The finding that kinectin was an autoantigen was verified in 9 out of 39 (23%) BD patient sera by immunoprecipitation of the in vitro translation products. Sera from controls showed no reactivity. The significance of kinectin as a participant in autoimmune pathogenesis in BD and the potential use of autoantibody to kinectin in serodiagnostics are discussed.
Highlights
Behçet's disease (BD) is a systemic vasculitic disease typified by a triad of symptoms including recurrent oral ulcers, genital ulcers and uveitis
The study subjects of 39 Chinese BD patients comprised 17 males and 22 females, mean age 37 ± 11.3 years old, who were divided into two subgroups: 25 typical BD patients (Group I, satisfying the International Criteria) and 14 clinically diagnosed BD patients who had recurrent oral ulcers and one of the symptoms of genital ulcers, eye symptoms or skin lesions as defined by the International Criteria, as well as additional symptom(s) closely related to BD as listed in the International Criteria, that is, gastrointestinal ulcerations, deep vein thrombosis or arthralgia/arthritis without evidence that the latter symptoms might be related to any other disease (Group II, defined as 'probable BD' in this study)
These antigens were detected in HeLa and T24 cells; the latter cell line was analyzed because our laboratory at The Scripps Research Institute has produced an excellent expression cDNA library from the T24 line and the positive result with the T24 cell extracts allowed us to screen the T24 library
Summary
Behçet's disease (BD) is a systemic vasculitic disease typified by a triad of symptoms including recurrent oral ulcers, genital ulcers and uveitis. The etiopathogenesis of the disease remains unclear but microbial agent triggers, environmental factors, genetic predisposition, neutrophil hyperfunction, endothelial cell dysfunction and immunological abnormalities involving both T and B cells have been implicated. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune rheumatic disease with autoantibodies against cellular ( nuclear) antigens, some of which are critically implicated in the autoimmune pathology while others provide valuable serodiagnostic markers for the disease. Sporadic reports on findings of autoantibodies in this disease have been described, such as antibodies to retinal antigen(s), heat shock protein (HSP) of some strains of Streptococcus sanguis cross-reactive with human HSP polypeptide [3], antibodies to endothelial cell antigens (AECA) and antibodies to α-tropomyosin [4,5], attesting to the complicated humoral immune disorders in this disease
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