Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies

Abstract

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity

“…Murine models have also provided evidence that gut barrier defects and translocation of commensals, their antigens, and in some cases live bacteria have been recoverable from draining lymph nodes and the liver ( 37 ). However, a subsequent report found sera from both patients with SLE as well as healthy controls had IgG and IgA antibodies reactive with E. gallinarum ( 38 ), suggesting this commensal is not a common driver of uncomplicated SLE. Taken together, dysfunctional intestinal barrier integrity has been documented in three lupus mouse models ( 37 , 39 , 40 ), while severe lupus-like disease arises in the B6.Sle1.Sle2.Sle3 mouse without evidence of altered gut barrier permeability or commensal translocation ( 34 ).…”

Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies

“…Therefore, pathogen-specific therapy can suppress host autoimmune processes without the use of immunosuppressants. More recently, another study showed that E. gallinarum is associated with autoimmune responses to autoantibodies such as anti-Ribosomal P, anti-dsDNA, and anti-Sm in patients with SLE ( 61 ). This study further confirmed that E. gallinarum is a specific pathogen of SLE-susceptible individuals.…”

Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis

“…There is evidence that intestinal expansion of this species leads to cross-reaction with lupus anti-double stranded DNA (dsDNA) antibodies and correlated with lupus nephritis. 38 Bagavant et al 54 also found an increase in Enterococcus gallinarum in patients with SLE and that this was significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. However, we cannot infer changes at the level of the species or genus based on changes at the level of the family, as determined by 16S RNA data.…”