Response to: ‘The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus’ by Zhang <i>et al</i> and the phylogeny of a candidate pathobiont in lupus nephritis

Silverman, Gregg J.; Azzouz, Doua F.

doi:10.1136/annrheumdis-2019-216523

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…25 In other diseases, at most only infrequent concordance between specific host-associated micro-organisms and pathology has been reported. 26 By contrast, evidence of RG expansions in patients with active SLE, and especially LN, has now been found in three US cohorts along with cross-sectional surveys of serum IgG anti-LG studies, 7 a Scandinavian cohort, 27 a large untreated cohort in China 28 and a French cohort. 29 The linkage between RG and SLE is also remarkable as RG bloom-associated disease flares occurred in individuals of diverse race and ethnicity (online supplemental table S1).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

Azzouz,

Chen,

Izmirly

et al. 2023

Ann Rheum Dis

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ObjectiveWhereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities.MethodsIn an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed.ResultsMultivariate analyses documented that, unlike healthy controls, significant temporal community-wide ecological microbiota instability was common in SLE patients, and transient intestinal growth spikes of several pathogenic species were documented. Expansions of only the anaerobic commensal,Ruminococcus (blautia) gnavus(RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares.ConclusionsOur findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.

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