Direct correlation between plasma microbial translocation and autoantibodies in first-degree relatives of patients with systemic lupus erythematosus

Abstract

Abstract Background The process of events underlying autoantibody production in systemic lupus erythematosus (SLE) is unknown. Methods Plasma from 36 female African-Americans (18 unrelated healthy controls (UHCs) and 18 first-degree relatives of SLE patients (FDRs)) were assessed for autoantibodies by autoantibody array, lipopolysaccharide (LPS) levels by the limulus amebocyte assay and microbiome by 16S rDNA analysis. Results Compared to UHCs, FDRs exhibited elevated plasma autoantibody levels but not similar total IgGs. The median plasma IgGs were 346 (interquartile range, 236–465) and 480 (286–891) for anti-double strand DNA (anti-dsDNA, P = 0.04, Mann-Whitney U-test), 3422 (2863–4076) and 4815 (3447–8464) for anti-single strand DNA (anti-ssDNA, P = 0.03), and 4593 (4050–5521) and 4714 (4004–5278) for total IgGs (P = 0.95), in UHCs and FDRs respectively. Furthermore, parent/child of patients exhibited elevated plasma LPS compared to UHCs. Plasma LPS levels were 59.1 (53.3–68.6) and 71.2 (62.2–80.4) for UHCs and parent/child of patients respectively (P = 0.03). Notably, plasma LPS was positively correlated with IgG anti-dsDNA (r = 0.53, P = 0.02, Spearman correlation) and anti-ssDNA (r = 0.53, P = 0.02) in FDRs but not in UHCs (P > 0.70). Plasma microbiome revealed a reduced diversity (P < 0.02) and lower abundance of Streptococcaceae (unadjusted P = 0.01, adjusted for multiple comparisons P = 0.10) in FDRs compared to UHCs. The ratios of Firmicutes to Bacteroidetes were 6.75 (0.66–42.5) in UHCs and 3.37 (0.63–22.5) in FDRs but did not achieve significance. Conclusion Taken together, these results indicate a possible role for plasma microbial translocation and microbiome composition in autoantibody development in SLE.