Background/Purpose: Neonatal lupus is linked to the presence of circulating anti-Ro antibodies in the mother. These antibodies are present in asymptomatic individuals, who in a subset years later progress to develop overt autoimmune disease. This study was initiated to investigate whether an environmental trigger such as oral colonization by autoreactivity-inducing commensals may contribute to pathgenesis. This goal was approached by leveraging agnostic profiling of the salivary microbiome to identify pathobionts associated with disease outcome in high titer anti-Ro positive women of children with neonatal lupus.

Methods: The study included 24 anti-Ro⁺ women from the Research Registry for Neonatal Lupus (RRNL) with nine being asymptomatic or having insufficient criteria for Sjögren’s Syndrome (SS) and/or ACR/SLICC SLE (incomplete diagnoses) and 9 SS, 2 SLE, and 4 SS/SLE (established diagnoses) . The rheumatologic diagnoses of the RRNL women were independently determined by two rheumatologists via questionnaire, telephone interview, and/or in-person history/physical exam, and review of medical records. An additional 7 healthy women served as controls. After extraction of host and non-host genomic DNA from saliva (without use of artificial saliva or stimulants), the microbiome was assessed by 16S rRNA gene library analysis using standard protocols (mean of 20k reads per sample). Operational taxonomic units (OTUs) were identified by closed-reference OTU-picking using Green Genes as reference. Shannon’s index, a mathematical measure of species diversity (H’) and relative abundance, was tested for differences using the Kruskal-Wallis tests.

Results: H’ was different for virtually all taxa. At the phylum level, H’ was significantly lower in RRNL vs controls (1.33 vs 1.53 respectively, p=0.018). Significance was retained down to the family level (2.46 vs 2.82 respectively, p=0.007). Contrasting RRNL with controls identified six phyla and 19 families having significant differences in relative abundance (p<0.05). For example, at the family level, Porphyromonadaceae, Fusobacteriaceae, Pasteurellaceae, and Flavobacteriaceae were less abundant in RRNL compared to controls (p=0.003, p=0.004, p=0.030, p=0.038, respectively). In contrast, Peptostreptococcaceae, Weeksellaceae, Coriobacteriaceae and Prevotellaceae were significantly more abundant (p=0.001, p=0.003, p=0.0081, p=0.0421, respectively) in the RRNL. Using a model with comparisons to healthy controls and with RRNL divided into the two subgroups (i.e., incomplete and complete, as described in the methods), the three-group test retained this pattern of significance and differential relative abundance down to the family phylogenetic level, except for Flavobacteriaceae which still showed a similar trend (p=0.08).

Conclusion: These data support a decrease in the diversity of the oral microbiota in anti-Ro positive women, especially in those with established autoimmune diseases such as SS. Our evidence of concurrent increases in relative abundance of organisms, such as inflammatory-provoking Prevotellaceae, may provide insight into disease evolution in a predisposed host.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/salivary-dysbiosis-correlates-with-clinical-status-of-anti-ro-positive-mothers-of-children-with-neonatal-lupus/