title: 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: OBJECTIVE
  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 immuno-assay.
  
  
  RESULTS
  Anti-CD38 aAb prevalence among new-onset 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 new-onset 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.
  
  
  CONCLUSIONS
  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 beta-cell function.
authors.affiliation: Department of Internal Medicine, University of Torino, Italy. roberto.mallone@unito.it
authors.forename: R
authors.initials: R
authors.lastname: Mallone
authors.forename: E
authors.initials: E
authors.lastname: Ortolan
authors.forename: S
authors.initials: S
authors.lastname: Pinach
authors.forename: M
authors.initials: M
authors.lastname: Volante
authors.forename: M M
authors.initials: MM
authors.lastname: Zanone
authors.forename: G
authors.initials: G
authors.lastname: Bruno
authors.forename: G
authors.initials: G
authors.lastname: Baj
authors.forename: T
authors.initials: T
authors.lastname: Lohmann
authors.forename: P
authors.initials: P
authors.lastname: Cavallo-Perin
authors.forename: F
authors.initials: F
authors.lastname: Malavasi
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000276:immunology*; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D002096:C-Peptide; C096322:ICA512 autoantibody; D008562:Membrane Glycoproteins; C024211:islet cell antibody; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D005968:Glutamate Decarboxylase; D002118:Calcium