Background: Recent evidence suggests the initiation of rheumatoid arthritis (RA) – related autoimmunity may occur by local citrullination at the oral mucosa and lungs. IgA antibodies are the hallmark of mucosal immunity; the majority of saliva IgA antibodies are locally produced whereas IgG antibodies are largely serum derived(.¹ Furthermore, IgA anti-CCP antibodies have recently been described in the sputum of at-risk individuals(.² The relative importance of the oral and lung mucosa in disease initiation is, however, unclear and the prevalence of saliva and sputum anti-CCP antibodies in the same at-risk individuals has not been reported.

Objectives: To investigate the prevalence of IgA anti-CCP antibodies in the saliva and sputum of seropositive individuals at risk of developing RA.

Methods: Anti-CCP positive individuals with no evidence of clinical synovitis (CCP+), anti-CCP positive RA patients (RA) and healthy controls (HC) matched for age and smoking status were recruited. Unstimulated saliva and serum samples were collected. Induced sputum samples were obtained using 7% saline via ultrasonic nebuliser (UltraNeb 3000 DA, Devilbiss, Germany). Sputum was mixed with phosphate buffered saline, mechanically disrupted and centrifuged to obtain supernatant. IgA and IgG anti-CCP antibodies (anti-CCP2, immunocap assay, Phadia) were measured in all saliva, sputum and serum samples. IgA and saliva/sputum IgG anti-CCP titres exceeding the 95th centile in HC were considered positive.

Results: 55 CCP+, 40 RA and 32 HC were recruited and had saliva and serum collected. 24 CCP+, 14 RA and 22 HC had sputum and serum collected. Of these, 23 CCP +and 7 RA patients provided simultaneous saliva, sputum and serum samples. 8/55 (15%) CCP +and 10/40 (25%) RA patients had positive saliva IgA anti-CCP levels compared with 1/31 (3%) HC. 23/54 (43%) CCP +and 21/48 (44%) RA patients had positive serum IgA anti-CCP levels compared with 1/32 (3%) HC (table 1). Of note, 7/18 (39%) patients with a positive saliva IgA anti-CCP test had a negative serum IgA anti-CCP test, suggesting localised production and accumulation of IgA anti-CCP antibodies rather than transfer from the serum. Only 1/24 CCP+ (4%) and 1/14 (7%) RA patients had positive sputum IgA anti-CCP levels. No patients had IgA anti-CCP detectable in both saliva and sputum samples.

Conclusions: We found an increased prevalence of saliva but not sputum IgA anti-CCP antibodies in seropositive at-risk individuals. These findings support the concept that localised RA-related autoimmunity in at risk individuals can be site specific. IgA anti-CCP antibodies at the oral mucosa precede arthritis and may represent an important step in the initiation and propagation of disease.

References

1. Brandtzaeg P. Ann NY Acad Sci 2007.
2. Willis, et al. Arthritis Rheum 2013.

Disclosure of Interest: None declared

DOI: 10.1136/annrheumdis-2018-eular.5287