کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10940910 | 1095530 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Autoantibodies against aromatic amino acid hydroxylases in patients with autoimmune polyendocrine syndrome type 1 target multiple antigenic determinants and reveal regulatory regions crucial for enzymatic activity
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کلمات کلیدی
TphAutoimmune polyendocrine syndrome type 1APECEDAPS-1BH4RIAGADTBSPAHBSA - BSAglutamic acid decarboxylase - glutamic acid dearboxylasebovine serum albumin - آلبومین سرم گاوstandard deviation - انحراف معیارTris buffered saline - تریس نمک بافرautoimmune regulator - تنظیم کننده autoimmunetyrosine hydroxylase - تیروزین هیدروکسیلازradioimmunoassay - رادیوایمونواسیautoimmune polyendocrinopathy candidiasis ectodermal dystrophy - سندرم تخمدان پلی کیستیPhenylalanine hydroxylase - فنیلالانین هیدروکسیلازAIRE - هواAromatic amino acid hydroxylase - هیدروکسیلاز اسید آمینه اسیدtryptophan hydroxylase - هیدروکسیلاز تریپتوفان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Patients with autoimmune polyendocrine syndrome type 1 (APS-1) frequently have autoantibodies directed against the aromatic amino acid hydroxylases tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH). We aimed to characterize these autoantibodies with regard to their antigenic determinants, their influence on enzymatic activity and their clinical associations. In particular, we wanted to compare autoantibodies against the two different isoforms of TPH, which display different tissue distribution. Using sera from 48 Scandinavian APS-1 patients we identified 36 patients (75%) with antibodies against one or more of these three enzymes. Antibodies against TPH1, but not TPH2, were associated with malabsorption in the whole Scandinavian cohort, while TH antibodies were associated with dental enamel hypoplasia in Norwegian patients. Subsequent experiments with selected patient sera indicated that while the C-terminal domain was the immunodominant part of TPH1, the epitopes of TPH2 and TH were mainly located in the N-terminal regulatory domains. We also identified a TPH1 specific epitope involved in antibody mediated inhibition of enzyme activity, a finding that provides new insight into the enzymatic mechanisms of the aromatic amino acid hydroxylases and knowledge about structural determinants of enzyme autoantigens. In conclusion, TPH1, TPH2 and TH all have unique antigenic properties in spite of their structural similarity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunobiology - Volume 218, Issue 6, June 2013, Pages 899-909
Journal: Immunobiology - Volume 218, Issue 6, June 2013, Pages 899-909
نویسندگان
Eirik Bratland, Ng'weina Francis Magitta, Anette Susanne Bøe Wolff, Trude Ekern, Per Morten Knappskog, Olle Kämpe, Jan Haavik, Eystein Sverre Husebye,