Islet cell antibodies ? Theoretical and practical implications

Lernmark, Åke; Baekkeskov, Steinunn

doi:10.1007/bf00257781

Cited by 53 publications

(18 citation statements)

References 19 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autoantibodies to an islet protein of M, 64,000 (64K), first described more than a decade ago ( 1,2), are present in most newly diagnosed IDDM patients and prediabetic first-degree relatives (3,4), may precede other antibody markers (4,5), are present in animal models of IDDM (6,7), and may have greater sensitivity, specificity, and predictive value for human IDDM than other established markers (3,5,8). The true utility of64K antibody measurement is unknown, however, since islet-based immunoprecipitation assays are expensive and laborious, preventing completion of large studies.…”

Section: Introductionmentioning

confidence: 99%

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Hagopian

Karlsen

Gottsäter³

et al. 1993

J. Clin. Invest.

205

105

View full text Add to dashboard Cite

At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy. (J. Clin. Invest. 1993. 91:368-374.)

show abstract

Section: Introductionmentioning

confidence: 99%

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Hagopian

Karlsen

Gottsäter³

et al. 1993

J. Clin. Invest.

205

105

View full text Add to dashboard Cite

show abstract

“…Other arguments lending support to the autoimmune theory of B-cell destruction are: (1) occasional associations of type 1 diabetes with other autoimmune endocrinopathies have been known for a long time ]39, 40]; (2) experimentally, insulitis can be produced by active immunization with insulin [41]; (3) indications of an altered cell-mediated immunity have been repeatedly reported [39]; (4) islet cell antibodies (ICA), with and without complement fixation, and islet cell surface antibodies (ICSA) can be demon strated in almost all newly diagnosed type 1 diabetics [42][43][44]; (5) studies in sponta neously diabetic BB-rats suggest that in these animals which serve as model of type 1 dia betes the disease can result from insulitisinduced, possibly immune-related B-cell de struction [45,46].…”

Section: Etiology and Pathogenesis Of Type 1 Diabetesmentioning

confidence: 99%

Islet Pathology and the Pathogenesis of Type 1 and Type 2 Diabetes mellitus Revisited

Klöppel

Löhr

Habich

et al. 1985

Pathol Immunopathol Res

341

294

View full text Add to dashboard Cite

“…Presumably, there is a sequence similar to that occurring in human Type I, insulin dependent diabetes mellitus (IDDM) in which deteriorating islet secretory cells release antigenic components and the immune system reacts by forming antibodies [Irvine et al, 1976;Lernmark et al, 1981]. The ICA serve as markers of islet cell degeneration in human beings and in monkeys at a time well before overt diabetes can be clinically diagnosed.…”

Section: Introductionmentioning

confidence: 99%

Islet cell antibodies in Sulawesi macaques

et al. 1999

View full text Add to dashboard Cite

Older monkeys of the Sulawesian species Macaca nigra spontaneously develop a lesion in the pancreatic islets of Langerhans in which there is deposition of amyloid and gradual degeneration of all cells, which can lead eventually to development of diabetes mellitus. Islet cell antibodies (ICA), formed in response to the release of cellular antigens, can be used to detect the islet lesion and to monitor the progression of each monkey toward diabetes. Numerous M. nigra and one M. tonkeana in captivity have been tested, but it is unknown whether the islet lesion occurs in monkeys in their natural habitat of Sulawesi. Blood samples collected from M. maurus, M. tonkeana, and hybrid M. maurus/tonkeana were assayed for ICA. When all monkeys were considered together, 33%' had ICA positive against beta cells and 14% had ICA positive against alpha and/or D cells. Appearance of ICA in blood of males was virtually the same as in females. These results are similar to those found in M. nigra examined in captivity. Since all Sulawesian species share a common genetic heritage, these results would support the appearance of this lesion in their natural habitat. Cause(s) for formation of the lesion and eventual development of diabetes are unknown. There may be genetic factors or genetic predisposition to environmental factors. If environmental factors are responsible, then they must be present not only in the wild, but either carried with the monkeys or universally available, since M. nigra born in captivity also develop the lesion and diabetes after physical maturity at ca. 7+ years. Am. J. Primatol. 47:223–229, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

Islet cell antibodies ? Theoretical and practical implications

Cited by 53 publications

References 19 publications

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Islet Pathology and the Pathogenesis of Type 1 and Type 2 Diabetes mellitus Revisited

Islet cell antibodies in Sulawesi macaques

Contact Info

Product

Resources

About