title: Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses.
abstract: Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment-further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD.
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Harlow
authors.affiliation: Medical Genetics Branch, NHGR, NIH, Bethesda, MD 20892, United States.
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States.
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Rosas
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States.
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Doyle
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Osorio
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Travers
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Camacho
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL 33136, United States. Electronic address: DAscherman@med.miami.edu.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
mesh_terms: D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000150:complications*; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018604:Epitope Mapping; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology; D008297:Male
chemical_list: D000906:Antibodies; D015415:Biomarkers; D018841:HSP90 Heat-Shock Proteins
keywords: Autoantibodies; Bronchoalveolar lavage fluid; Citrullination; HSP90; Interstitial lung disease; Rheumatoid arthritis