THU0348 ALTERED IMMUNE RECOGNITION OF SPECIFIC GUT BACTERIA BY IMMUNOGLOBULINS IN EARLY SYSTEMIC SCLEROSIS

Abstract

Background:Gastrointestinal tract (GIT) involvement is highly prevalent in systemic sclerosis (SSc) and associates with GIT symptoms that are present early and progress over time. Changes in gut microbiota are often reported in inflammatory disease settings but whether GIT symptoms associate with altered immune recognition of specific gut bacteria in early SSc is unknown.Objectives:Here, we profiled Ig coating patterns of gut bacteria in early disease from two well-characterized SSc cohorts to determine if the pattern and extent of bacterial immunoglobulin (Ig) coating differs in early SSc.Methods:We collected fecal material from early SSc patients (<36 months from time of diagnosis) at Oslo and Lund University Hospitals and from healthy age and gender matched controls (HC). To assess whether adaptive immunity was triggered against gut microbiota in early disease, we sorted and sequenced IgA, IgM and IgG coated bacteria from fecal samples by flow cytometry and performed 16s rRNA sequencing to compare the relative Ig coating of early SSc patients to HC. Data was resolved to the family level, rarefied to 5101 reads and converted to relative abundance. Taxonomic profiles, relative abundance, IgA, IgM and IgG coating patterns and extent of Ig coating were assessed. Unadjusted p-values <0.05 were defined as significant.Results:We included 50 SSc patients (26 from Oslo, 24 from Lund) with early SSc and 9 gender and age matched HC. Mean age of SSc patients at time of inclusion was 53 years, mean time since diagnosis was 13 months; 82% were female, 61% had limited cutaneous SSc and 43% were anti-centromere antibody positive. In all, 82% were treatment naïve while 18% had received either cyclophosphomide or mycophenolate mofetil immunosuppressants. We found increased relative abundance of IgA coated Desulfovibrionaceae in both SSc cohorts compared to HC and increased IgM and IgG coating of Veillonellaceae and Streptococcaceae (Figure 1). All of these bacteria have previously been associated with other autoimmune diseases or pro-inflammatory status; Desulfovibrionaceae to immune activation in the gut, and Veillonellaceae and Streptococcaceae to other chronic inflammatory and fibrotic conditions. While abundance of IgA coated Desulfovibrionaceae was higher in cyclophosphomide or mycophenolate mofetil-treated SSc patients than untreated patients, Veillonellaceae and Streptococcaceae were not affected by treatment. A lower abundance of IgA and IgM coated Akkermansiaceae; and IgM and IgG coated Bifidobacteriaceae was detected in treated compared to treatment naïve early SSc patients (Figure 2).Conclusion:We find the pattern and extent of Ig coating to inflammatory-associated gut bacteria differs between treatment-naïve, early SSc patients treated with cyclophosphomide or mycophenolate mofetil and HC which suggests immunosuppressive treatments may modify gut microbiota in SSc. Overall these findings support the involvement of altered immune recognition of specific gut bacteria in early SSc.Disclosure of Interests:Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Kristofer Andréasson: None declared, Simen Hyll Hansen: None declared, Simon Midtvedt: None declared, Håvard Fretheim: None declared, Henriette Didriksen Consultant of: Actelion, Torhild Garen: None declared, Espen Bækkevold: None declared, Øyvind Midtvedt: None declared, Roger Hesselstrand: None declared, Brian K Chung: None declared, Øyvind Molberg: None declared