Background/Purpose: Rheumatoid arthritis (RA) is a complex autoimmune disorder in which several genetic and environmental factors play a role. Recent data suggest that the gut and oral microbiome might potentially contribute to the priming of an aberrant systemic immune response characteristic of RA. Among studied microbiota, both Porphyromonas gingivalis in the oral cavity and Prevotella copri in the gut have been implicated. Intriguingly, airway abnormalities and increased lung tissue citrullination is found in both RA patients and individuals at at-risk for the development of disease. This suggests the possibility that the lung could be yet another site of autoimmunity generation in RA. Our objective was to study whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity.

Methods: Bronchoalveolar lavage (BAL) samples from 20 subjects with RA, 10 with sarcoidosis and 24 healthy controls were obtained by research bronchoscopy. 16S rDNA sequencing was performed to define microbiota composition. Levels of arginine/citrulline were measured in BAL fluid using GC-MS for all samples. Autoantibodies, including anti-CCP, RF and ACPAs were also measured in BAL and sera of RA subjects. Statistical analysis was performed using wilcoxon test and Spearman correlation.

Results: There were no differences in demographic or clinical characteristics (including smoking status) between groups. 16S sequencing data showed similar alpha/beta diversity between RA and DC groups, but significantly different from controls. Taxonomic comparison between groups was performed using LEfSe, which revealed several significant differences (LDA score>2). Multiple taxa, including Rhanella and Rhodanobacter were present only in the RA and DC groups, but completely absent from healthy subjects (p<0.001). While RA BAL samples were enriched with Sphingobacteria, sarcoidosis BAL was enriched with Bacteroidia, Rhizobiales, Nitrospirales, and Campylobacter. GC-MS showed similar levels of arginine and citrulline in BAL for the sarcoidosis and RA groups. Raoultella and Barnesiella correlated with CCP2 levels in BAL (rho= 0.49 and 0.47; p-value= 0.026 and 0.032 respectively). Serum levels of CCP-IgA had a negative correlation with Massilia and Tannerella (rho= -0.63 and 0.53; p-value 0.003 and 0.016, respectively), and a positive correlation with Vagococcus and Lactobacillus (rho= 0.59 and 0.54; p-value 0.006 and 0.014, respectively). Unclas_Lactobacillales also had a positive correlation with serum levels of RF-IgA (rho= 0.71; p-value <0.001). Serum levels of anti-CCP2 antibodies had a positive correlation with Porphyromonas, Rahnella and Chryseobacterium(rho=0.46, 0.46 and 0.45; p-value= 0.03, 0.03 and 0.04 respectively).

Conclusion: Despite the relatively small number of samples analyzed, several taxonomic differences were noted between groups. Correlations between relative abundance of specific taxa in RA BAL with serum autoantibodies (i.e., anti-CCP) support an association between the lung microbiome and the host immune phenotype in RA. Further evaluation of functional aspects of this microbiome may provide further insights into its possible contribution to RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-lung-microbiome-in-rheumatoid-arthritis-and-associated-localsystemic-autoimmunity/