Autoantibody fine specificity restriction is associated with clinical response in RA treated with abatacept and methotrexate.

OBJECTIVE

Anti-modified protein antibodies (AMPA) are central in rheumatoid arthritis (RA). We evaluated whether changes in fine specificities (FS) of anti-citrullinated protein antibodies (ACPA) and anti-CarP antibodies relate to clinical prognosis in RA patients treated with abatacept (ABA) plus methotrexate (MTX).

METHODS

A multiplex bead immunoassay measured 6 ACPA FS and 1 anti-CarP FS in 59 anti-CCP+ RA patients (IgG, IgA). Disease activity (DAS28-CRP) and FS levels were assessed at baseline (M0) and 6 months (M6).

RESULTS

After 6 months of ABA+MTX, several FS decreased with frequent negative seroconversion (NS). Higher baseline anti-citrullinated α-enolase (ACit-ENO1) IgG levels predicted better outcome (decrease of -0.17 DAS28 score per decile, 95 % CI -0.27 to -0.07, p = 0.03). Among patients with ≥1 positive FS at M0, a higher number of NS across 14 FS (IgG/IgA) correlated with greater improvement (-0.27 DAS28 score per antibody, 95 % CI -0.39 to -0.15, p < 0.0001).

CONCLUSIONS

In this cohort of limited size, clinical response at M6 with ABA+MTX treatment was associated with the restriction of the autoantibody repertoire of IgG and IgA classes in RA patients.