Human Monoclonal Autoantibodies That React with Multiple Endocrine Organs

Satoh, Jo; Prabhakar, Bellur S.; Haspel, Martin V.; Ginsberg‐Fellner, Fredda; Notkins, Abner Louis

doi:10.1056/nejm198307283090405

Cited by 139 publications

(59 citation statements)

References 23 publications

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“…F A E 7 was derived from b l o o d o b t a i n e d 1 y e a r b e f o r e onset of Type 1 diabetes, but the a n t i b o d y did not represent the typical features k n o w n for I C A -p o s i t i v e sera. D u e to its cross-reactivity with h u m a n pituitary cells, thyroid, exocrine p a n c r e a t i c epithelia, and pancreas ducts, F A E 7 must be c o n s i d e r e d as a polyreactive IgM a n t i b o d y like the previous islet-reactive h u m a n m o n o c l o n a l IgMantibodies derived from patients with Type 1 d i a b e t e s [13]. Such polyreactive I g M -a n t i b o d i e s also occur in nor-mal individuals unrelated to autoimmune diseases [14].…”

Section: Discussionmentioning

confidence: 94%

Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies

et al. 1993

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Summary.The first human monoclonal islet cell antibodies of the IgG class (MICA 1-6) obtained from an individual with Type 1 (insulin-dependent) diabetes mellitus were cytoplasmic islet cell antibodies selected by the indirect immunofluorescence test on pancreas sections. Surprisingly, they all recognized the 64 kDa autoantigen glutamate decarboxylase. In this study we investigated which typical features of cytoplasmic islet cell antibodies are represented by these monoclonals. We show by double immunofluorescence testing that MICA 1-6 stain pancreatic beta cells which is in agreement with the beta-cell specific expression of glutamate decarboxylase. In contrast an islet-reactive IgM monoclonal antibody obtained from a pre-diabetic individual stained all islet cells but lacked the tissue specificity of MICA 1-6 and must therefore be considered as a polyreactive IgM-antibody. We further demonstrate that MICA 1~5 revealed typical features of epitope sensitivity to biochemical treatment of the target tissue which has been demonstrated for islet cell antibodies, and which has been used to argue for a lipid rather than a protein nature of target antigens. Our results provide direct evidence that the epitopes recognized by the MICA are destroyed by methanol/chloroform treatment but reveal a high stability to Pronase digestion compared to proinsulin epitopes. Conformational protein epitopes in glutamate decarboxylase therefore show a sensitivity to biochemical treatment of sections such as ganglioside epitopes. MICA 1-6 share typical features of islet cell and 64 kDa antibodies and reveal that glutamate decarboxylase-reactive islet cell antibodies represent a subgroup of islet cell antibodies present in islet cell antibody-positive sera.

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Section: Discussionmentioning

confidence: 94%

Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies

et al. 1993

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“…The human T cell line HD-Mar, lkndly provided by Dr H. Ben-Bassat (Ben-Bassat et al, 1980), the human B cell lines 209 (a gift of Dr G.Lenoir, Lyon, France) and GM 4672 (Satoh et al, 1983) were grown in RPMI 1640 supplemented with 15% fetal calf serum (FCS). HeLa cells were grown in Dulbecco's modified Eagle's medium containing 10% FCS.…”

Section: Cells and Reagentsmentioning

confidence: 99%

Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

et al. 1987

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“…The second is that the serum contains antibodies that recognize common proteins or epitopes in different organs. Using hybridoma technology or Epstein-Barr virus (EBV) transformation, it is now becoming possible to address this question by studying the reactivity ofhuman monoclonal autoantibodies (12)(13)(14). In this paper, we describe a simple and rapid screening procedure for detecting human monoclonal autoantibodies that react with pancreatic islets, and show that many of these antibodies also react with the thyroid and other human tissues.…”

Section: Introductionmentioning

confidence: 99%

Human monoclonal autoantibodies that react with both pancreatic islets and thyroid.

Garzelli¹,

Taub²,

Jenkins³

et al. 1986

J. Clin. Invest.

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Transformation of human peripheral blood lymphocytes with Epstein-Barr virus and rapid screening on rat insulinoma cells by an enzyme-linked immunosorbent assay were used to identify monoclonal autoantibodies that reacted with human pancreatic islets. Six such monoclonal autoantibodies were isolated and cloned. All six also were found to react with human thyroid. It is concluded that lymphocytes able to make autoantibodies that react with both the pancreas and thyroid are common in the human B cell repertoire.

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Human Monoclonal Autoantibodies That React with Multiple Endocrine Organs

Cited by 139 publications

References 23 publications

Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies

Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies

Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

Human monoclonal autoantibodies that react with both pancreatic islets and thyroid.

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