Anti-CD38 autoantibodies: characterisation in new-onset type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies.
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.
Mallone
R
R
Department of Internal Medicine, University of Torino, Italy. roberto.mallone@unito.it
Ortolan
E
E
Pinach
S
S
Volante
M
M
Zanone
M M
MM
Bruno
G
G
Baj
G
G
Lohmann
T
T
Cavallo-Perin
P
P
Malavasi
F
F
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
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