Human Anti-CD38 Autoantibodies Raise Intracellular Calcium and Stimulate Insulin Release in Human Pancreatic Islets

Antonelli, Alessandro; Baj, Germano; Marchetti, Piero; Fallahi, Poupak; Surico, N; Pupilli, Cinzia; Malavasi, Fabio; Ferrannini, Ele

doi:10.2337/diabetes.50.5.985

Cited by 51 publications

(53 citation statements)

References 31 publications

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“…The prevalence of anti-CD38 antibodies in this Type II diabetic cohort was 8.4%, which is slightly lower than that observed in Japanese [20] or Italian Type II diabetes patients [21,22]. Given the relatively large sample size in these studies, this result probably refers to the inter-ethnic variability of autoimmune phenomena.…”

Section: Discussioncontrasting

confidence: 62%

“…The autoradiografic signals were abolished by preincubating anti-CD38 positive sera with recombinant CD38 but not with LacZ-MBP [21,22]. When anti-CD38 positive and anti-CD38 negative sera were screened against recombinant CD38 from P. pastoris, a band of approximately 30 kilo-Dalton, corresponding to the soluble CD38, and a higher molecular mass species (probably due to self-aggregation) were observed for all six anti-CD38 positive sera, whereas no signal was detected with six anti-CD38 negative sera.…”

Section: Detection Of Anti-cd38 Antibodies In Human Serummentioning

confidence: 99%

“…Recently, the presence of autoantibodies to CD38 has been described both in Japanese [20] and Caucasian [21,22] patients with Type II diabetes. These findings raise the question of whether Type II diabetic patients with anti-CD38 autoantibodies have a clinical phenotype similar to that of anti-GAD positive patients, who share features of latent autoimmune diabetes (LADA).…”

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confidence: 99%

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Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

et al. 2002

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Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulindependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects).Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1*02 compared with 38% of anti-CD38 negative (p=0.04).On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2±3.1 U/mol, mean ± SD) but not in anti-CD38 positive patients (5.6±2.9) as compared with patients free of autoimmunity (4.5±4.6, p=NS).In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5′ end of intron 1 or the 5′ and 3′ untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence. [Diabetologia (2002[Diabetologia ( ) 45:1298[Diabetologia ( -1306

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Section: Discussioncontrasting

confidence: 62%

Section: Detection Of Anti-cd38 Antibodies In Human Serummentioning

confidence: 99%

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confidence: 99%

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Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

et al. 2002

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“…The large preponderance of agonistic features for anti-CD38 aAbs is also in line with the clinical and metabolic correlations observed. Indeed, the Ca 2+ -mobilising activity of anti-CD38 aAbs was shown not only to be effective in lymphocytic cell lines [25], but also in purified human islets, where it is coupled to stimulation of insulin secretion [30]. In this scenario, the observed in vitro agonistic features of anti-CD38 aAbs could be operating in vivo as well.…”

Section: Discussionmentioning

confidence: 98%

“…The majority of these aAbs showed agonistic properties, capable of triggering Ca 2+ release from CD38 + target cells [25]. Anti-CD38 + sera incubated with purified islet cells induced not only Ca 2+ mobilisation, but also insulin secretion, with a direct correlation between the two effects [24,30]. In agreement with these experimental findings, anti-CD38 + Type II diabetic patients were characterized by higher residual beta-cell function and higher BMI, i.e., a phenotype opposite to that of LADA [25].…”

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confidence: 99%

Anti-CD38 autoantibodies: Characterisation in new-onset Type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies

Mallone¹,

Ortolan²,

Pinach³

et al. 2002

Diabetologia

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Aims/hypothesis. Serum anti-CD38 autoantibodies (aAbs) have been reported in 17 to 19% of patients with long-standing Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus. Whether these aAbs are also found in new-onset Type I diabetes and in Latent Autoimmune Diabetes in Adults (LADA) is not known, as is their relationship with conventional islet aAbs. Methods. These issues were addressed by studying new-onset Type I and LADA diabetic cohorts with a recently developed anti-CD38 enzymatic immunoassay. Results. Anti-CD38 aAb prevalence among newonset Type I patients (3.8%) was lower than previously found in long-standing Type I diabetes (11.7%, as defined with the 97.5 percentile cutoff; p=0.01), suggesting a late appearance of these aAbs. Among LADA patients, 14.9% were anti-CD38 + . Anti-CD38 were only associated with anti-GAD aAbs in newonset Type I diabetes. Although the CD38 target molecule was expressed in human pancreatic islets, anti-CD38 aAbs did not contribute to the islet cell antibody (ICA) immunofluorescence reactivity. All the positive sera analysed for Ca 2+ release were found to mobilise it. In agreement with these agonistic features, anti-CD38 + new-onset Type I patients showed higher fasting C-peptide values as compared to negative counterparts; the association was stronger when the analysis was limited to the agonistic anti-CD38 + sera. A similar trend was found among LADA patients. Conclusion/interpretation. Anti-CD38 aAbs are distinct markers of islet autoimmunity which are more prevalent in long-standing disease, as opposed to the other known islet aAbs. Their in vitro agonistic properties could be operating in vivo as well, as they identify sub-groups of patients with higher residual betacell function. [Diabetologia (2002[Diabetologia ( ) 45:1667[Diabetologia ( -1677

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Vaccinations and Type 1 Diabetes

Antonelli

Ferrari

Domenicantonio

et al. 2015

Vaccines and Autoimmunity

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Human Anti-CD38 Autoantibodies Raise Intracellular Calcium and Stimulate Insulin Release in Human Pancreatic Islets

Cited by 51 publications

References 31 publications

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

Anti-CD38 autoantibodies: Characterisation in new-onset Type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies

Vaccinations and Type 1 Diabetes

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