ESPE Abstracts

Introduction: The envelope protein of Human Endogenous Retrovirus type W (HERV-W-Env) has been shown to be associated with type 1 diabetes (T1D) pathogenesis in adults patients. This protein is expressed in pancreas of T1D patients and it seems to correlate with macrophage infiltrations. In vitro and in vivo studies have demonstrated that HERV-W-Env inhibits insulin secretion and promotes hyperglycemia. Furthermore, HERV could be implicated in other auto-immune disorders. The purpose of this study was to investigate the prevalence of HERV-W-Env protein and its corresponding RNA in pediatric T1D patients.

Methods: We performed a preliminary study in a monocentric pediatric cohort (n=19). Inclusion criteria were T1D, absence of any acute inflammatory or infectious disease or anti-inflammatory medication. The results were compared to a previously studied cohort of 30 healthy adults. HERV-W-Env expression was assessed by Elisa in sera and by quantitative reverse transcription PCR (RT-qPCR) in peripheral blood mononuclear cells (PBMC). Other clinical data evaluated in the pediatric group were: age, age at onset of diabetes, length of diabetes, BMI, daily insulin dose, fasting glycemia, HbA1C, C-peptide, ACTH, TSH, total Cholesterol, HDL, LDL, Ratio HDL/total cholesterol, HLA typing, specific auto-antibodies (anti GAD, anti-insulin, ant- IA2).

Results: HERV-W-Env protein was significantly detected in T1D pediatric patients compared to control individuals (P<0.01). We detected HERV-W-env RNA expression in PBMC of 7/19 (37%) T1D patients (not statistically significant compared with control individuals). 7/17 (41%) sera of T1D patients were positive for HERV-W-Env, whereas 4/30 (13%) control individuals had low positivity of unknown origin. HERV-W-Env expression was not related to age, age at onset, HbA1c or diabetes duration. Daily insulin dose was positively correlated with HERV-W-Env expression (P<0.05). Additionally, none of the T1D pediatric patients positive for HERV-W-Env had detectable C-peptide. Interestingly we found a positive correlation HERV-W-Env expression and TSH levels (P<0.05).

Conclusions: HERV-W-Env protein was significantly detected in about 40% of T1D pediatric patients. Levels of HERV-W-Env were positively correlated with daily insulin dose, suggesting that HERV-W-Env may be associated with complete insulin deficiency. As HERV could be implicated in other auto-immune disorders and could affect endothelial cells and Schwann cells, a close monitoring of T1D comorbidities in these patients seems essential. Overall, our results suggest that a pediatric subgroup of T1D might benefit from an anti-HERV-W-Env therapy.