Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis

• Published in: Nature reviews. Rheumatology Vol. 10; no. 11; pp. 645 - 653
• Main Authors: Catrina, Anca I., Ytterberg, A. Jimmy, Reynisdottir, Gudrun, Malmström, Vivianne, Klareskog, Lars
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2014; Nature Publishing Group
• Subjects: 692/420/256; 692/420/2780; 692/699/1670/498; Antibodies; Antigens; Arthritis, Rheumatoid - immunology; Autoantibodies - immunology; Citrulline - immunology; Development and progression; Disease; Etiology; Genetic aspects; Genetic research; Genetic susceptibility; Genotype & phenotype; Humans; Immune system; Inflammation; Inflammation - immunology; Irritants - immunology; Joints - immunology; Lung - immunology; Lungs; Medicin och hälsovetenskap; Medicine & Public Health; Pathogenesis; Peptides, Cyclic - immunology; Proteins; review-article; Rheumatoid arthritis; Rheumatology; Smoking - immunology
• ISSN: 1759-4790; 1759-4804; 1759-4804
• DOI: 10.1038/nrrheum.2014.115

Key Points Autoantibodies against post-translational modified citrullinated proteins, so-called anti-citrullinated protein antibodies (ACPAs), define a distinct clinical RA phenotype; this phenotype is characterized by an increased frequency of early inflammatory lung changes The presence of ACPAs before signs of inflammation in joints suggests that immunity against citrullinated proteins is initiated outside the joint Changes in the lung and enrichment of ACPAs in the lungs (bronchoalveolar lavage fluid) occur in both individuals at risk of developing RA as well as patients with early RA The lung, therefore, might be a site of initiation of immunity to citrullinated proteins Early targeting of the immune reactions in the lung might be a new approach to modulate disease Autoantibodies towards citrullinated proteins define a distinct clinical subtype of rheumatoid arthritis (RA). Here, the authors describe events triggering immunity against citrullinated proteins and argue that this immune response might be initiated outside the joint, pointing to the lungs as a possibly important site of initiation of these events. Rheumatoid arthritis (RA) is a prototype for a criterion-defined inflammatory disease, for which the aetiology and initial molecular pathogenesis has been elusive for a long time. We describe in this Review how studies on the interplay between specific immunity, alongside genetic and environmental predisposing factors, provide new tools to understand the molecular basis of distinct subsets of the disease. A particular emphasis is on the possibility that pathogenic immune reactions might be initiated at other sites than the joints, and that the lungs could harbour such sites. New data strengthen this concept, showing that local immunity towards citrullinated proteins and accompanying inflammation might be present in the lungs early during disease development. This progress makes RA an interesting case for the future development of therapies that might be directed against disease-inducing immunity even before inflammation and destruction of joints has begun.