Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children

Ivan Gerling, S. Baekkeskov, A. Lernmark

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation of IgM from IgG to prevent interference between the two antibody classes. Plasma samples from 10 newly diagnosed IDDM children and 10 healthy controls were precipitated with polyethylene glycol (PEG), and the crude Ig was subjected to Sephacryl S-300 chromatography to separate IgM and IgG. ICA determined by indirect immunofluorescence on frozen sections of human pancreas showed reduced background immunofluorescence intensity in the purified fractions compared with crude plasma. The number of ICA-positive samples among the IDDM patients increased from 7/10 in plasma to 9/10 in the IgG fraction. There was an increase in the ICA titer in 6/9 of the positive samples. All purified IgM samples were ICA negative. Immunoprecipitation experiments by using Nonidet P-40 detergent lysates of [35S]methionine-labeled neonatal rat islets demonstrated that the 64,000 autoantibodies were in the IgG fraction. We found 7/10 IDDM samples to be positive, whereas all controls were negative. The background in the autoradiographic analysis was markedly reduced in the IgG fractions compared with immunoprecipitates with crude or PEG-purified plasma and the IgM fraction. ICA titers did not correlate to the ability of the IgG fraction to precipitate the 64,000 autoantigen. It is concluded that both the ICA and 64,000 autoantibodies are primarily of the IgG class at the time of clinical onset of IDDM, and that purification of IgG from human IDDM plasma facilitates the detection of the rat islet cell 64,000 antigen.

Original languageEnglish (US)
Pages (from-to)3782-3785
Number of pages4
JournalJournal of Immunology
Volume137
Issue number12
StatePublished - 1986
Externally publishedYes

Fingerprint

Islets of Langerhans
Autoantibodies
Immunoglobulin G
Type 1 Diabetes Mellitus
Insulin
Immunoglobulin M
Antigens
islet cell antibody
Immunoglobulin Isotypes
Histocompatibility Antigens Class II
Autoantigens
Antigen Presentation
Frozen Sections
Indirect Fluorescent Antibody Technique
Immunoprecipitation
Methionine
Detergents
Fluorescent Antibody Technique
Chromatography
Pancreas

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children. / Gerling, Ivan; Baekkeskov, S.; Lernmark, A.

In: Journal of Immunology, Vol. 137, No. 12, 1986, p. 3782-3785.

Research output: Contribution to journalArticle

@article{5a8487ec472c41f289a1b6e95a9b0152,
title = "Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children",
abstract = "There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation of IgM from IgG to prevent interference between the two antibody classes. Plasma samples from 10 newly diagnosed IDDM children and 10 healthy controls were precipitated with polyethylene glycol (PEG), and the crude Ig was subjected to Sephacryl S-300 chromatography to separate IgM and IgG. ICA determined by indirect immunofluorescence on frozen sections of human pancreas showed reduced background immunofluorescence intensity in the purified fractions compared with crude plasma. The number of ICA-positive samples among the IDDM patients increased from 7/10 in plasma to 9/10 in the IgG fraction. There was an increase in the ICA titer in 6/9 of the positive samples. All purified IgM samples were ICA negative. Immunoprecipitation experiments by using Nonidet P-40 detergent lysates of [35S]methionine-labeled neonatal rat islets demonstrated that the 64,000 autoantibodies were in the IgG fraction. We found 7/10 IDDM samples to be positive, whereas all controls were negative. The background in the autoradiographic analysis was markedly reduced in the IgG fractions compared with immunoprecipitates with crude or PEG-purified plasma and the IgM fraction. ICA titers did not correlate to the ability of the IgG fraction to precipitate the 64,000 autoantigen. It is concluded that both the ICA and 64,000 autoantibodies are primarily of the IgG class at the time of clinical onset of IDDM, and that purification of IgG from human IDDM plasma facilitates the detection of the rat islet cell 64,000 antigen.",
author = "Ivan Gerling and S. Baekkeskov and A. Lernmark",
year = "1986",
language = "English (US)",
volume = "137",
pages = "3782--3785",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children

AU - Gerling, Ivan

AU - Baekkeskov, S.

AU - Lernmark, A.

PY - 1986

Y1 - 1986

N2 - There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation of IgM from IgG to prevent interference between the two antibody classes. Plasma samples from 10 newly diagnosed IDDM children and 10 healthy controls were precipitated with polyethylene glycol (PEG), and the crude Ig was subjected to Sephacryl S-300 chromatography to separate IgM and IgG. ICA determined by indirect immunofluorescence on frozen sections of human pancreas showed reduced background immunofluorescence intensity in the purified fractions compared with crude plasma. The number of ICA-positive samples among the IDDM patients increased from 7/10 in plasma to 9/10 in the IgG fraction. There was an increase in the ICA titer in 6/9 of the positive samples. All purified IgM samples were ICA negative. Immunoprecipitation experiments by using Nonidet P-40 detergent lysates of [35S]methionine-labeled neonatal rat islets demonstrated that the 64,000 autoantibodies were in the IgG fraction. We found 7/10 IDDM samples to be positive, whereas all controls were negative. The background in the autoradiographic analysis was markedly reduced in the IgG fractions compared with immunoprecipitates with crude or PEG-purified plasma and the IgM fraction. ICA titers did not correlate to the ability of the IgG fraction to precipitate the 64,000 autoantigen. It is concluded that both the ICA and 64,000 autoantibodies are primarily of the IgG class at the time of clinical onset of IDDM, and that purification of IgG from human IDDM plasma facilitates the detection of the rat islet cell 64,000 antigen.

AB - There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation of IgM from IgG to prevent interference between the two antibody classes. Plasma samples from 10 newly diagnosed IDDM children and 10 healthy controls were precipitated with polyethylene glycol (PEG), and the crude Ig was subjected to Sephacryl S-300 chromatography to separate IgM and IgG. ICA determined by indirect immunofluorescence on frozen sections of human pancreas showed reduced background immunofluorescence intensity in the purified fractions compared with crude plasma. The number of ICA-positive samples among the IDDM patients increased from 7/10 in plasma to 9/10 in the IgG fraction. There was an increase in the ICA titer in 6/9 of the positive samples. All purified IgM samples were ICA negative. Immunoprecipitation experiments by using Nonidet P-40 detergent lysates of [35S]methionine-labeled neonatal rat islets demonstrated that the 64,000 autoantibodies were in the IgG fraction. We found 7/10 IDDM samples to be positive, whereas all controls were negative. The background in the autoradiographic analysis was markedly reduced in the IgG fractions compared with immunoprecipitates with crude or PEG-purified plasma and the IgM fraction. ICA titers did not correlate to the ability of the IgG fraction to precipitate the 64,000 autoantigen. It is concluded that both the ICA and 64,000 autoantibodies are primarily of the IgG class at the time of clinical onset of IDDM, and that purification of IgG from human IDDM plasma facilitates the detection of the rat islet cell 64,000 antigen.

UR - http://www.scopus.com/inward/record.url?scp=0023029021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023029021&partnerID=8YFLogxK

M3 - Article

C2 - 3537124

AN - SCOPUS:0023029021

VL - 137

SP - 3782

EP - 3785

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -