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

Abstract

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

Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

“…In advanced stages of DR the prevalence of antibodies declines and this could mark pericyte loss and disease progression [ 184 ]. Moreover, antibodies against CD38 (antigen that is present on retinal pericytes) have been found in the serum of diabetic patients [ 185 – 188 ]. Further studies are needed to elucidate the role of these antibodies as biomarkers in DR.…”

Decreased ADP-Ribosyl Cyclase Activity in Peripheral Blood Mononuclear Cells from Diabetic Patients with Nephropathy

“…In agreement with these functional features, the presence of anti-CD38 autoantibodies in type 2 diabetic patients was associated with significantly higher levels of fasting plasma C-peptide and insulin, as compared with anti-CD38 negative subjects. Thus, anti-CD38 autoimmunity might indicate a relative protection against beta-cell failure and a lower risk of insulin requirement [52, 54, 55]. Previous reports on the clinical characteristics of anti-CD38 autoantibodies carriers have not gone into depth on diabetic complications, although the possible exacerbation of diabetic complications by the agonistic effect of anti-CD38 autoantibodies on PBMCs was noted by Mallone et al [51].…”