In rheumatoid arthritis patients, total IgA1 and IgA2 levels are elevated: implications for the mucosal origin hypothesis

OBJECTIVE: Mucosal initiated immune responses may be involved in the pathophysiology of RA. The most abundant immunoglobulin at mucosal surfaces is IgA, of which two subclasses exist: IgA1 and IgA2. IgA2 is mainly present at mucosal sites and has been ascribed pro-inflammatory properties. As IgA subclasses might provide insights into mucosal involvement and pro-inflammatory mechanisms, we investigated IgA responses in sera of RA patients. METHODS: In two cohorts of RA patients, the EAC and IMPROVED, total IgA1 and IgA2 were measured by ELISA. Furthermore, IgA subclass levels of RF and anti-citrullinated protein antibodies (anti-CCP2) were determined. The association of these IgA subclass levels with CRP and smoking was investigated. RESULTS: Total IgA1 and IgA2 were increased in RA patients compared with healthy donors in both cohorts. This increase was more pronounced in seropositive RA vs seronegative RA. For RF and anti-CCP2, both IgA1 and IgA2 could be detected. No strong associations were found between IgA subclasses (total, RF and anti-CCP2) and CRP. In smoking RA patients, a trend towards a selective increase in total IgA2 and RF IgA1 and IgA2 was observed. CONCLUSION: RA patients have raised IgA1 and IgA2 levels. No shift towards IgA2 was observed, indicating that the increase in total IgA is not due to translocation of mucosal IgA into the bloodstream. However, mucosal inflammation might play a role, given the association between smoking and total IgA2 levels. Despite its pro-inflammatory properties, IgA2 does not associate strongly with pro-inflammatory markers in RA patients.