Combined analysis of islet cell antibodies which cross-react with mouse pancreas, antibodies to the Mr 64,000 islet protein, and antibodies to glutamate decarboxylase in subjects at risk for IDDM

Chaillous, Lucy; Elmansour, A.; Charbonnel, B.; Saı̈, Pierre; Delamaire, M.; Maugendre, D; Allannic, H; Rohmer, V.; Joseph, Mina; Limal, Jean-Marie; Lecomte, P.

doi:10.1007/s001250050137

Cited by 13 publications

(4 citation statements)

References 48 publications

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“…In the non-diabetic population, the prevalence of ICA (4.9%) was also significantly higher than in the general population of our country (<1%), or even than in French schoolchildren (1.8%) (35) but was not very different from the prevalence of ICA in relatives of diabetic patients (36). This prevalence of ICA was slightly higher than reported in other studies on Caucasian and Japanese patients (37)(38)(39).…”

Section: Discussioncontrasting

confidence: 57%

“…It is now well established that the 64 kDa protein identified by immunoprecipitation method is GAD (7) and we have previously demonstrated that antibodies to the 64 kDa protein and to GAD were strongly associated in diabetic patients and their ICA-positive relatives (36,41). The Second GAD Workshop showed that the mean sensitivity of radiobinding assays (76.2%) was higher than for ELISA (36.5%) and immunotrapping assays (49.9%) (29).…”

Section: Discussionmentioning

confidence: 96%

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Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Maugendre¹,

Verite²,

Guilhem³

et al. 1997

European Journal of Endocrinology

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The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes.Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis.To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 96%

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Maugendre¹,

Verite²,

Guilhem³

et al. 1997

European Journal of Endocrinology

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“…It has been shown that the prediction of IDDM can be considerably improved by the addition of insulin autoantibodies (IAA), autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to 37 kDa (37 kDa-ab) and 40 kDa (40 kDa-ab) antigens in ICA positive individuals [7][8][9][10][11][12]. Primary screening for either IAA or GADA alone, however, has proved to be less specific than ICA testing [7,[13][14][15].…”

mentioning

confidence: 99%

Combined screening for autoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM

et al. 1996

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To determine the value of antibodies to the intracytoplasmic domain of the tyrosine phosphatase IA-2 (anti-IA-2ic) and glutamic acid decarboxylase (GADA) for identification of subjects at risk for insulin-dependent diabetes mellitus (IDDM) we investigated 1238 first degree relatives of patients with IDDM for the presence of anti-IA-2ic and GADA and compared the results with cytoplasmic islet cell antibodies (ICA). Anti-IA-2ic were observed in 54 (4.4%) first degree relatives, in 51 of 86 (59.3%) ICA positive relatives and in 3 of 4 individuals who developed overt IDDM within a follow-up period of 1 to 28 months. GADA were found in 78 of 1238 (6.3%) first degree relatives. They were detected in 22 of 35 (62.9%) sera with ICA alone and in 1 of 3 subjects with anti-IA-2ic in the absence of ICA. Of the 1238 subjects 37 (3.0%) sera were positive for all three antibodies. Both anti-IA-2ic and GADA were positively correlated with high levels of ICA. Anti-IA-2ic and GADA were detected in 39.1 and 47.8% of subjects with ICA of less than 20 Juvenile Diabetes Foundation units (JDF-U) but in 66.7 and 76.2% of individuals with ICA of 20 JDF-U or more, respectively (p < 0.05). The levels of ICA and GADA in first degree relatives with at least one additional marker were significantly higher than in subjects with ICA alone (p < 0.005) or GADA alone (p < 0.03). The combination of anti-IA-2ic and GADA identified 84.9% of all ICA positive subjects and 93.7% of individuals with high level ICA (> or = 20 IDF-U). All 4 individuals who progressed to IDDM had either IA-2ic or GADA. Our data indicate that primary screening for anti-IA-2ic and GADA provides a powerful approach with which to identify subjects at risk for IDDM in large-scale population studies which may represent the basis for the design of new intervention strategies.

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“…ICA found in Type 1 diabetic patients are heterogeneous immunoglobulins directed against selected antigens in the islets of Langerhans [1, 5, 6]. The ICA assay continues to be one of the best, if not the best, immunologic markers for the subsequent development of Type 1 diabetes in first-degree relatives of diabetic patients [7, 8, 9, 10].…”

Section: Introductionmentioning

confidence: 99%

Sera from Children with Type 1 Diabetes mellitus React against a New Group of Antigens Composed of Lysophospholipids

Bleich¹,

Polak

Chen³

et al. 1999

Horm Res Paediatr

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Several autoantibodies related to Type 1 diabetes mellitus and their corresponding autoantigens have been previously identified. While peptide antigens are more widely recognized, lipid antigens like sulfatides and gangliosides are also known epitopes for the diabetic humoral immune response. Islet cell antibodies (ICA) in Type 1 diabetes are heterogeneous immunoglobulins directed against selected antigens in the islets of Langerhans. Moreover, ICA may be the best predictive marker of disease in family members of patients with Type 1 diabetes. The aims of this study were: (1) to purify lipids from porcine pancreas that contain ICA epitopes; (2) to characterize these lipid antigens, and (3) to use the purified lipids in an assay to detect antibodies in patients with Type 1 diabetes. A unique family of 4 lysophospholipids, 1 fully characterized as lysophosphatidylmyoinositol, partially inhibited ICA staining, and therefore, were considered to be candidate antigens for an ICA immunoassay. Using a dot blot immunoassay, we detected antibodies directed against these phospholipids in 28 out of 46 (61%) diabetic sera, while detecting only 1 false positive out of 28 nondiabetic sera (3.6%; p < 0.0001 comparing diabetic vs. nondiabetic serum). Therefore, lysophospholipid immunoassay positivity is present in sera of Type 1 diabetic patients. Furthermore, we detected 15 out of 23 ICA-negative diabetic sera (65.2%), showing that our phospholipid immunoassay does not correlate with ICA positivity.

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Combined analysis of islet cell antibodies which cross-react with mouse pancreas, antibodies to the Mr 64,000 islet protein, and antibodies to glutamate decarboxylase in subjects at risk for IDDM

Cited by 13 publications

References 48 publications

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Combined screening for autoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM

Sera from Children with Type 1 Diabetes mellitus React against a New Group of Antigens Composed of Lysophospholipids

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