1143-P: Elevated Serum IgA and the Gut Microbiome in Pediatric Type 1 Diabetes (T1D)

Abstract

Elevated serum IgA occurs in ~20% of children with new onset T1D, although its potential role in T1D pathogenesis is not understood. Gut dysbiosis is present at onset of T1D and is strongly associated with its pathogenesis. Mucosal IgA is well known to influence the microbiome and vice versa. In animal models, serum IgA responds to microbiome changes, thereby inducing a protective response to gut invasion by pathogens. However, the relationship between gut microbiome and serum IgA in humans with T1D is unknown. Thus, we aimed to assess if elevated serum IgA is associated with gut dysbiosis at T1D onset. We enrolled 47 children between 7/2021 and 9/2022: New onset T1D with elevated serum IgA (T1D-Hi-IgA, n=14), new onset T1D with normal serum IgA (T1D-Nl-IgA, n=18) and controls (siblings of new onset T1D, n=15). Exclusions: <2 yrs age; antibiotics; probiotics; inflammatory bowel disease; celiac disease; or acute illness <10 days of stool collection. Demographic and clinical variables, diet questionnaires and stool were collected. Stool microbiome was determined via 16Sv4 rDNA sequencing. Differences in alpha and beta diversity along with taxa abundance were assessed. We found that the relative abundance of members of families Oscillospiraceae and Lachnospiraceae, both of which contain butyrate producers, were significantly associated with elevated IgA irrespective of T1D status (p<0.05); higher in T1D-Hi-IgA vs T1D-Nl-IgA (p<0.05); yet similar in T1D-Hi-IgA vs controls. Measures of alpha diversity, including richness and evenness, were also increased in T1D-Hi-IgA vs T1D-Nl-IgA, though these differences did not reach significance (richness: p=0.074; evenness: p=0.135). Similar results were observed for beta diversity. In sum, in children with new onset T1D, elevated serum IgA is associated with beneficial microbial taxa such as butyrate producers, with a trend towards increased diversity, similar to healthy siblings. Further studies are needed to understand its involvement in T1D pathogenesis. Disclosure A.Thakkar: None. M.J.Redondo: None. J.Hajjar: None. J.Petrosino: None. K.L.Hoffman: Consultant; Cooper Surgical. J.Cormier: None. M.Ahmed: None. X.C.Huang: None.