Type 1 Diabetes (T1D) is an autoimmune disease caused by the destruction of beta cells. Because both viral infections and cytokines are suggested to play a role in T1D pathogenesis, we analyzed the viral infection and cytokine profiles of T1D patients compared to age and sex-matched healthy controls. The median age in years of T1D patients was 16.9 ± 1.14 (mean ± SEM) and 17.88 ± 0.78 for the healthy subjects. The disease duration in years was 8 ± 1.1 (n=25, 13 females, 12 males) . We first assessed the viral infection history using a PepSeq-based highly multiplexed serological assay. This assay covers the full proteomes of human viruses and determines serum immunoglobulin-G (IgG) reactivity to 30mer viral peptides. We showed that enterovirus (EV) seropositivity were distinct between the two groups, with more EV-C and EV-D positives in the T1D samples and more EV-A and EV-B positives in the controls. The trends for the viruses showing higher seropositivity were primarily driven by the female patients. To determine the cytokine profiles, we measured the serum levels of 48 cytokines, chemokines and growth factors. Interestingly, we only observed significant sex-specific differences. For example, anti-inflammatory cytokines interleukin-4 (IL-4) , IL-13, IL-22, and pro-inflammatory cytokines IL-17E and tumor necrosis factor-β were significantly lower in female patients as compared to female controls. Male patients had increased levels of epidermal growth factor and platelet-derived growth factor compared to healthy males. IL-22 was unique, unlike the decrease in female patients, it increased in the male patients compared to healthy males. Altogether, we identified sex-dependent alterations in the cytokine profiles and observed a difference in EV exposure profiles between T1D patients and healthy subjects. Determining sex-specific cytokine profiles and the potential role of viral infections in T1D pathogenesis will help us to gain deeper insight into the pathogenesis of the disease.


K.Girdhar: n/a. A.Pina: None. J.Momirov: None. M.A.Atkinson: None. J.Ladner: None. E.Altindis: None.


NIH NIDDK 1K01DK117967-G. Harold & Leila Y. Mathers Foundation grants to EA

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