Differences in Epitope Restriction of Autoantibodies to Native Human Insulin (IAA) and Antibodies to Heterologous Insulin (IA)

Differences in Epitope Restriction of Autoantibodies to Native Human Insulin (IAA) and Antibodies to Heterologous Insulin (IA)
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天然人胰岛素 (IAA) 自身抗体和异源胰岛素 (IA) 抗体表位限制的差异

DOI:
10.2337/diab.36.1.66
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发表时间:
1987
期刊:
影响因子:
7.7
通讯作者:
T. Wilkin
T. Wilkin
中科院分区:
医学1区
文献类型:
--
作者:
J. Diaz;T. Wilkin

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采用直接免疫特异性酶联免疫吸附试验(ELISA)和胰岛素与Sepharose beads共价偶联的间接吸附实验,研究了胰岛素自身抗体(IAA)和胰岛素抗体(IA)与高纯度胰岛素变体和片段的结合谱。来自胰岛素初始的非糖尿病患者的10个含有laa的血清中,有5个与全人(H)胰岛素结合,而不与全猪(P)或全牛(B)胰岛素结合。这些血清结合H型胰岛素b链,但不结合P型胰岛素b链或脱盐的P型胰岛素,表明它们依赖于苏氨酸B30的存在。其他5个含有iaa的血清结合H、P、B和脱盐猪胰岛素,但只有1个结合分离的B链。胰岛素治疗的糖尿病患者10种含ia的血清均与H、P、B和脱盐P胰岛素结合,但只有1种与人(和猪)的B链结合。进一步与羊、兔、大鼠和豚鼠胰岛素的结合研究证实了含5iaa血清的H(苏氨酸B30)特异性。然而,当胰岛素外源性给药时,B30残基似乎不占优势。相反,IA主要结合到链或构象决定因素涉及两个链。对具有代表性的H胰岛素特异性IAA血清的Scatchard分析表明,它具有单一的结合亲和力,而对具有代表性的ia糖尿病血清的分析表明,它具有几种不同的亲和力。
The binding profiles of insulin autoantibodies (IAA) and insulin antibodies (IA) to highly purified species variants and fragments of insulin were studied in direct immunospecific enzyme-linked immunosorbent assay (ELISA) and indirect absorption experiments with insulins covalently coupled to Sepharose beads. Five of 10 lAA-containing sera from insulin-naive nondiabetics that bound whole human (H) insulin did not bind whole porcine (P) or whole bovine (B) insulins. These sera bound H insulin B-chain but not P B-chain or desalanated P insulin, suggesting they were dependent on the presence of threonine B30. The other 5 IAA-containing sera bound H, P, B, and desalanated porcine insulins, but only 1 bound isolated B-chains. All 10 IA-containing sera from insulin-treated diabetics bound H, P, B, and desalanated P insulins, but only 1 bound to human (and porcine) B-chain. Further binding studies with ovine, rabbit, rat, and guinea pig insulins confirmed the H (threonine B30) specificity of the 5 IAA-containing sera. B30 residues do not appear to be dominant, however, when insulin is administered exogenously. Instead, IA bind predominantly to Achain or conformational determinants involving both chains. Scatchard analysis of a representative H insulin-specific IAA serum suggested that it contained a single binding affinity, whereas analysis of a representative IA-diabetic serum suggested it contained several different affinities.
DOI: --
发表时间: 1983
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Bender,TP;Schroer,J;Claflin,JL
通讯作者: Claflin,JL