Islet cell antibodies and insulin autoantibodies as predictive markers in the non-obese diabetic mouse

Reddy, Shiva; Bibby, N.J.; Rb, Elliott

doi:10.1016/0896-8411(90)90091-6

Cited by 17 publications

(25 citation statements)

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“…Guinea pig anti-ovine insulin serum was available in this laboratory and is specific for beta cells (Reddy et al 1988(Reddy et al , 2005. Rabbit anti-glucagon serum was purchased from Dako, Glostrup, Denmark and sheep anti-somatostatin serum was from Guildhay Limited, Guidford, Surrey, UK.…”

Section: Primary Antibodiesmentioning

confidence: 99%

Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study

et al. 2007

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During type 1 diabetes, most beta cells die by immune processes. However, the precise fate and characteristics of beta cells and islet autoimmunity after onset are unclear. Here, the extent of beta cell survival was determined in the non-obese diabetic (NOD) mouse during increasing duration of disease and correlated with insulitis. Pancreata from female NOD mice at diagnosis and at 1, 2, 3 and 4 weeks thereafter were analysed immunohistochemically for insulin, glucagon and somatostatin cells and glucose transporter-2 (glut2) and correlated with the degree of insulitis and islet immune cell phenotypes. Insulitis, although variable, persisted after diabetes and declined with increasing duration of disease. During this period, beta cells also declined sharply whereas glucagon and somatostatin cells increased, with occasional islet cells co-expressing insulin and glucagon. Glut2 was absent in insulin-containing cells from 1 week onwards. CD4 and CD8 T cells and macrophages persisted until 4 weeks, in islets with residual beta cells or extensive insulitis. We conclude that after diabetes onset, some beta cells survive for extended periods, with continuing autoimmunity and expansion of glucagon and somatostatin cells. The absence of glut2 in several insulin-positive cells suggests that some beta cells may be unresponsive to glucose.

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Section: Primary Antibodiesmentioning

confidence: 99%

Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study

et al. 2007

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“…These islet peripheral eells were shown to contain giucagon immunoreactivity by double immunofluorescence staining (S, Reddy, unpublished observations). A minority of ICA-positive sera showed immunoreaetion towards the giucagon eells only (Reddy et at.. 1988)-Representative photomicrographs of the above ICA patterns are shown in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

“…1981;Betterle ct ai, 1982;Baekkeskov, Dyrbcrg & Lernmark, 1984;Dyrberg et ai. 1984;Srikanta et ai, 1986;Takei et ai, 1986;Reddy. Bibby & Elliott.…”

Section: Introductionunclassified

Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice

Reddy

Bibby

1990

Clinical and Experimental Immunology

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SUMMARYWe have previously shown the presence of circulating islet cell cytoplasmic antibodies (ICA) and insulin autoantibodies (IAA) in the NOD mouse before onset of insulin-dependent diabetes mellitus (IDDM), Here we have determined the levels ofthe two autoantibodies in 28 female NOD miee longiludinaliy from approximately day 40 to day 250, to examine their ontogeny, association and predictive value for diabetes. All animals (11 diabetic, 17 non-diabetie) showed varying levels of ICA at some stage, while IAA aetivity was found in 21 out of 28 mice. Expression ofboth the markers was seen in more than half of the animals by day 60. with higher levels and rates oecurring subsequently in both diabetie and non-diabetic groups. The expression of ICA did not always correlate with that of IAA. There was no apparent diflferenee in the ontogeny of ICA and IAA between the two groups. During the study period the number of animals with ICA was similar in the two groups, while the number of those with IAA was higher in the diabetic animals. In this group deelining and rising levels of ICA were seen just before elinical diabetes with frequent peaks of IAA. In the same animals, eight out of 11 mice showed eo-expression of high levels of both markers either intermittently or f>ersistently prior to onset, whereas only one non-diabetic animal showed this. We conclude that the ontogeny and serum level of ICA or TAA alone could not be used to prediet Ihe clinical onset of diabetes in these animals. However, co-expression of high levels ofboth markers prior to onset may suggest a strong predisposition to clinical diabetes. This may have relevance to attempts to predict the onset of IDDM in humans who have one or both of these immunologieal markers.

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“…Autoreactive T cells are detectable in NOD mice within 2 wk of weaning (3,7), and peri-insulitis is slowly established over the next several weeks (8). Progression to invasive insulitis is prominent by 2-3 mo, with the beginning of significant islet destruction and consequent autoantibody production (9). The pace of ␤-cell destruction peaks close to overt disease, at 5-7 mo of age (10).…”

Section: N Autoimmune (Insulin-dependent or Type I) Diabetes Autormentioning

confidence: 98%

Peptide Dose, MHC Affinity, and Target Self-Antigen Expression Are Critical for Effective Immunotherapy of Nonobese Diabetic Mouse Prediabetes

Winer

Gunaratnam

Astsatourov

et al. 2000

The Journal of Immunology

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Cross-reactive T cells that recognize both Tep69 (dominant nonobese diabetic (NOD) T cell epitope in ICA69 (islet cell autoantigen of 69 kDa)) and ABBOS (dominant NOD T cell epitope in BSA) are routinely generated during human and NOD mouse prediabetes. Here we analyzed how systemic administration of these mimicry peptides affects progressive autoimmunity in adoptively transferred and cyclophosphamide-accelerated NOD mouse diabetes. These models were chosen to approximate mid to late stage prediabetes, the typical status of probands in human intervention trials. Unexpectedly, high dose (100 μg) i.v. ABBOS prevented, while Tep69 exacerbated, disease in both study models. Peptide effects required cognate recognition of endogenous self-Ag, because both treatments were ineffective in ICA69null NOD congenic mice adoptively transferred with wild-type, diabetic splenocytes. The affinity of ABBOS for NOD I-Ag7 was orders of magnitude higher than that of Tep69. This explained 1) the expansion of the mimicry T cell pool following i.v. Tep69, 2) the long-term unresponsiveness of these cells after i.v. ABBOS, and 3) precipitation of the disease after low dose i.v. ABBOS. Disease precipitation and prevention in mid to late stage prediabetes are thus governed by affinity profiles and doses of therapeutic peptides. ABBOS or ABBOS analogues with even higher MHC affinity may be candidates for experimental intervention strategies in human prediabetes, but the dose translation from NOD mice to humans requires caution.

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Islet cell antibodies and insulin autoantibodies as predictive markers in the non-obese diabetic mouse

Cited by 17 publications

References 0 publications

Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study

Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study

Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice

Peptide Dose, MHC Affinity, and Target Self-Antigen Expression Are Critical for Effective Immunotherapy of Nonobese Diabetic Mouse Prediabetes

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