Salivary dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus

Abstract

Mothers giving birth to children with manifestations of neonatal lupus (NL) represent a unique population at risk for the development of clinically evident pathologic autoimmunity since many are asymptomatic and only become aware of anti-SSA/Ro positivity (Anti-Ro+) based on heart block in their fetus. Accordingly, we hypothesized that the microbiome in saliva is associated with the development of autoreactivity and in some cases the progression in health status from benign to overt clinical disease including Sjögren's Syndrome (SS) and Systemic Lupus Erythematosus (SLE). The study comprised a clinical spectrum of anti-Ro+ mothers, all of whom gave birth to a child with NL: 9 were asymptomatic or had an undifferentiated autoimmune disease (Asym/UAS) and 16 fulfilled criteria for SS and/or SLE. Microbial diversity was reduced across all levels from kingdom to species for the anti-Ro+ mothers vs healthy controls (HC); however, there were no significant differences between Asym/UAS and SS/SLE mothers. Relative abundance of Proteobacteria and more specifically class Betaproteobacteria decreased with clinical severity (HC<Asym/UAS<SS/SLE). These ordered differences were maintained through the taxonomic hierarchy to three genera (Lautropia, Comamonas, and Neisseria) and species within these genera (L. mirabilis, N. flavescens and N. oralis). Biometric analysis comparing von Willebrand Factor domains present in human Ro60 with L. mirabilis proteins support the hypothesis of molecular mimicry. These data position the microbiome in the development of anti-Ro reactivity and subsequent clinical spectrum of disease.

Salivary dysbiosis in Sjögren’s syndrome and a commensal-mediated immunomodulatory effect of salivary gland epithelial cells

“…There may be some common critical features among these bacteria which await further exploration. The species A. parvulum, enriched in pSS patients, was found to have molecular mimicry with Ro60 54 and has also been reported to induce pancolitis in colitis-susceptible interleukin-10-deficient mice 55 . Further studies focusing on the interaction of A. parvulum with SGECs are therefore worthwhile.…”

Gut dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus

“…As previously described, 7 subjects were healthy controls or mothers enrolled in the Research Registry for Neonatal Lupus (RRNL). 8 All subjects signed informed consent for participation in the study approved by the NYU Grossman School of Medicine Institutional Review Board (IRB) in accordance with the Helsinki Declaration of 1975.…”

“…FASTQ files were processed using the Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline. 7 Reads with low-quality scores (phred < 25) were trimmed using Trim Galore and filtered in DADA2 if the maximum expected error count was greater than 2 per read. Chimeras were identified and removed following DADA2 protocol.…”

“…A subset of women had four-digit HLA alleles imputed from single nucleotide polymorphism (SNP) data from the Illumina Infinium Immunochip array using the program HIBAG. 7 , 20 The remaining women were assigned genotypes of 11 loci within HLA Class I and Class II, using the commercial platform of GenDx (Utrecht, the Netherlands). Briefly, genomic DNA (gDNA) was extracted and purified (QIAamp DNA Blood Mini Kit; Qiagen) from peripheral blood.…”

Lactobacillus Acidophilus Supplementation Exerts A Synergistic Effect on Tacrolimus Efficacy by Restoring Th17/Treg Imbalance in Lupus-Prone Mice via the SIGNR3 Pathway

“…Bacterial dysbiosis is seen in SLE patients and, to some extent, in murine models of lupus [16][17][18][19]. Furthermore, the dysbiosis is not only detected in the intestinal microbiota, but also in the oral mucosa and skin of lupus-affected subjects [20][21][22]. Therefore, bacterial dysbiosis may be related to the clinical status, or even the dietary metabolism, of lupus patients [23][24][25].…”