Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation

Abstract

Identical citrullinated peptides are present in bronchial and synovial tissues, which may be used as immunological targets for antibodies of patients with RA. The data provide further support for a link between lungs and joints in RA and identify potential targets for immunity that may mediate this link.

Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis

“…Interestingly, increased expression of citrullinated proteins in RA was present in smokers as well as in ACPA-positive non-smokers, suggesting that factors other than smoking might also contribute to generation of citrullinated epitopes in the lungs. Identification of shared citrullinated epitopes in the lungs and joints of patients with RA 9 together with local enrichment of ACPA in the bronchoalveolar lavage (BAL) of patients with early untreated RA and in the induced sputum of arthritis-free individuals at risk for developing RA10 support the notion that RA-associated autoimmunity might indeed initiate in the lung compartment 11. In line with this, ectopic lymphoid structures containing citrullinated protein-binding B cells have previously been reported in patients with established RA and associated lung disease 12.…”

Rheumatoid arthritis-associated lung disease

“…These antibodies may be present in the serum for several years before clinical disease onset [15,16]. Both rheumatoid factor and anti-CCP have been linked to the development of ILD, particularly when present in high titres [4,[17][18][19][20][21]. Anti-CCP antibodies have also been associated with the development of airway disease [2].…”

“…Additionally, a form of reactive lymphoid tissue known as inducible bronchus-associated lymphoid tissue (BALT) has been found in patients with rheumatoid arthritis-related lung disease and is associated with local production of inflammatory cytokines and anti-CCP antibodies [24]. A recent study examined the protein content in tissue samples obtained from lung and synovial biopsies of patients with rheumatoid arthritis, and found identical citrullinated vimentin peptides in both sites [18].…”

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

“…В других исследованиях было показано, что АЦБ обнару-живаются в мокроте здоровых людей, «серопозитивных» по АЦБ или имеющих семейный анамнез по РА [131]. Вы-явлена ассоциация между развитием бронхоэктазов, фиб-роза легких и увеличением концентрации АЦБ [132], об-разованием ростковых центров и накоплением В-клеток и плазматических клеток в ткани легких АЦБ-позитив-ных людей, у которых в последующем развилcя РА [133], и увеличением содержания цитруллинированных белков (виментин) в бронхиальной и синовиальной тканях [134]. Интересно, что на ранней стадии РА, предшествующей поражению суставов, преобладает синтез аутоантител IgA-изотипа [37,49,57,135,136].…”