title: The lung microbiota in early rheumatoid arthritis and autoimmunity.
abstract: Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity.
  
  
  
  16S rRNA gene high-throughput sequencing was utilized to compare the bacterial community composition of bronchoalveolar lavage fluid (BAL) in patients with early, disease-modifying anti-rheumatic drugs (DMARD)-naïve RA, patients with lung sarcoidosis, and healthy control subjects. Samples were further assessed for the presence and levels of anti-citrullinated peptide antibodies (including fine specificities) in both BAL and serum.
  
  
  
  The BAL microbiota of RA patients was significantly less diverse and abundant when compared to healthy controls, but similar to sarcoidosis patients. This distal airway dysbiosis was attributed to the reduced presence of several genus (i.e., Actynomyces and Burkhordelia) as well as reported periodontopathic taxa, including Treponema, Prevotella, and Porphyromonas. While multiple clades correlated with local and systemic levels of autoantibodies, the genus Pseudonocardia and various related OTUs were the only taxa overrepresented in RA BAL and correlated with higher disease activity and erosions.
  
  
  
  Distal airway dysbiosis is present in untreated early RA and similar to that detected in sarcoidosis lung inflammation. This community perturbation, which correlates with local and systemic autoimmune/inflammatory changes, may potentially drive initiation of RA in a proportion of cases.
authors.affiliation: Division of Rheumatology, NYU School of Medicine, New York, NY, USA. Jose.Scher@nyumc.org.
authors.forename: Jose U
authors.initials: JU
authors.lastname: Scher
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Vijay
authors.initials: V
authors.lastname: Joshua
authors.affiliation: Institute for Research in Public Health, Valencia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Artacho
authors.affiliation: Division of Rheumatology, NYU School of Medicine, New York, NY, USA.
authors.forename: Shahla
authors.initials: S
authors.lastname: Abdollahi-Roodsaz
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Öckinger
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Kullberg
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Sköld
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Clemente
authors.affiliation: Institute for Research in Public Health, Valencia, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Ubeda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, NYU School of Medicine, New York, NY, USA.
authors.forename: Leopoldo N
authors.initials: LN
authors.lastname: Segal
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anca I
authors.initials: AI
authors.lastname: Catrina
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016516:CD4-CD8 Ratio; D002956:Citrulline / Q000276:immunology / Q000378:metabolism; D064806:Dysbiosis / Q000382:microbiology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008297:Male; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017565:Sarcoidosis, Pulmonary / Q000276:immunology* / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D012336:RNA, Ribosomal, 16S; D002956:Citrulline