Changes in Intestinal Microflora Correlate with Disease Activity in Patients with Lupus Erythematosus
The role of intestinal microflora in the pathogenesis of autoimmune diseases, including lupus erythematosus, has been discussed for a long time. An American study discovered a specific bacterium whose proliferation in the intestine correlates not only with the occurrence of the disease but also with its activity.
Intestinal Microflora and Lupus
Only recently have technologies become available that allow for deeper exploration of the vast number of commensals in the intestinal microflora. It was previously proven that patients with lupus erythematosus have less diversity in their intestinal microflora, and simultaneously have an imbalance between different types of bacteria. However, the specifics of the composition of intestinal flora in patients with active disease had not been characterized until now.
Study Process and Results
In a study by authors from several American universities, stool and serum samples were collected from 61 female patients diagnosed with systemic lupus erythematosus (SLE) and 17 controls. Identification of microorganisms in the stool using 16S rRNA analysis and analysis of antibodies in the serum was performed on two independent cohorts of patients with SLE.
In individuals suffering from SLE, a lower species diversity of the intestinal microbiome was proven, which was most conspicuous in patients with a high SLEDAI score (SLE Disease Activity Index). The presence of the bacterium Ruminococcus gnavus (RG) from the Lachnospiraceae family was found to be 5 times higher in the gut of patients with lupus erythematosus. The proliferation of RG in the intestine correlated with an increase in antibodies (IgG) in serum for only 1 of the 8 tested strains. The level of these anti-RG antibodies was directly proportional to the SLEDAI score. Additionally, an inverse relationship was found between the level of anti-RG antibodies and the C3 and C4 components of complement, and a direct correlation was found with the levels of interleukin 6 and interferon α2.
The highest levels of anti-RG antibodies were found in patients with active lupus nephritis in both independent cohorts. Furthermore, the study revealed intestinal barrier damage in SLE, which may allow intestinal commensals or their fragments to exit the intestinal lumen.
Significance of Results for Practice and Further Research
The results of this study open new research areas on how the proliferation of certain intestinal bacteria affects the pathogenesis of SLE and immune complex-mediated pathogenesis of lupus nephritis. These findings may also be used to develop tests to assess the risk of developing lupus nephritis.
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Source: Azzouz D., Omaberkova A., Heguy A. et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis 2019; 78 (7): 947–956, doi: 10.1136/annrheumdis-2018-214856.
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