Patients with SLE show over-representation of Blautia genus in microbiome

SAN DIEGO — The pathogenesis of lupus nephritis may be linked to immunity to an intestinal commensal Lachnospiraceae species, according to findings presented during a plenary session here at the American College of Rheumatology Annual Meeting.

“That we can find any type of pattern is remarkable but has to due to the power of computational analysis,” Gregg J. Silverman, MD, director of the NYU Laboratory of B-Cell Immunobiology and professor of medicine and pathology at the NYU School of Medicine, told Healio Rheumatology. “We identified, based on as much information as you can get from this ribosomal gene, what appeared to be an over-representation in lupus patients of a single, anaerobic cocci representation in the fecal samples that we believe represents what is in the intestine.”

To find a pattern or patterns about the interface of systemic lupus erythematosus (SLE) with the gut microbiome, researchers obtained blood and fecal samples from 61 patients. Patients with selective IgA deficiency, history of prior cytotoxic drugs or antibiotics within 4 months were excluded from the study. Fecal 16S rRNA next-generation sequencing was performed and sera was profiled for autoantibodies. Two independent cohorts were also studied.

Silverman said the intestinal microbiome from patients with SLE showed decreased species richness diversity as compared with healthy people, while the microbiota of patients in clinical remission was most like that of healthy people. Additionally, patients with high disease activity had the most pronounced reductions in taxonomic complexity.

Among patients with SLE, the Blautia genus was 5 times more common than in healthy people, Silverman said. There was also a significant correlation between the distribution of SLEDAI scores and anti-strain IgG antibody levels.

“Patients with low-disease activity had less of these bacteria. The sicker you are, based on the SLE disease activity index, the more of this bacterial species you have,” he said.

High IgG anti-RG2 levels identified patients with lupus nephritis in three independent cohorts. Silverman said additional prospective studies of the infection cohorts are needed.

“We hope that treatment in the future will no longer require non-selective agents that destroy the immune system. It is not just about a non-specific immune response anymore. It is about a focused antibody-specific response. Understanding what is being targeted and having a test – a metric – to study this response should allow us to better define the therapy and not have to resort to a cancer therapy that destroys the immune system,” Silverman told Healio Rheumatology. – by Kristine Houck, MA, ELS

Reference:
Silverman GJ. Abstract 1786. Presented at: American College of Rheumatology Annual Meeting; Nov. 4-8, 2017; San Diego.

Disclosure: Silverman reports no relevant financial disclosures.