Fc receptors for IgG (Fcg R) play important roles in immune complex (IC)-mediated inflammation. Studies abrogating Fcg R actions have shown reduction of disease activity in animal models of arthritis. Monocytes are precursor cells of macrophages and osteoclasts, cell types that are highly involved in joint inflammation processes in rheumatoid arthritis (RA). We have investigated if antibody levels and monocytic Fc receptor expression and function in early RA are affected by anti-rheumatic treatment.
Twenty sero-positive steroid- and DMARD naive early RA patients and thirty-three healthy controls (HC), gender- and age-matched, were included. The majority of patients were anti-citrullinated protein antibody (ACPA) positive. If not contraindicated treatment with Methotrexate + steroids was initiated. Patients were evaluated before and after 3-4 months of therapy. At follow up patients were grouped in good responders or non responders using EULAR response criteria.
Inflammatory laboratory parameters and immunoglobulins (Ig) were analyzed at the Akademiska University hospital laboratory with standardized procedures. Expression of Fc receptor for IgA (CD89) and IgG (FcγRIII, CD16; FcγRIIa, CD32a; FcγRIIb, CD32b; FcγRI, CD64) on CD14 positive monocytes were analyzed with flow cytometry. Fcg R function was evaluated with IgG1 and IgG3 immune complex (IC) binding and IgG stimulated TNFa -production. DAS28, HAQ and patient reported VAS-scores for pain, global assessment and morning stiffness defined disease activity.
At inclusion RA patients displayed elevated levels of total IgG, IgG1 and IgG3 compared to HC. Expression of CD64 (frequency of cells and mean fluorescence intensity) and surface bound IgG on CD64 positive cells were significantly increased in RA patients. The Fcg R function in the patients was altered: a decrease in IC binding was observed, but monocytic TNFa -production was comparable with HC, except for non-responders who at baseline presented lower TNFa release when stimulated with IgG1. IgG and IgA levels correlated positively with the number of CD64/CD16 positive monocytes. Fc receptor expressions and function correlated with disease activity parameters. ACPA levels showed no correlations with FcR expressions or disease activity parameters.
At follow up mean DAS28 had decreased from 5.26 to 3.65 and mean HAQ from 0.95 to 0.45. The patients presented with significantly decreased levels of total Ig isotypes, IgG subclasses, ACPA and rheumatoid factor (RF) isotypes. Good responders excelled by down regulating CD64, decreasing CD16 on CD64 positive cells and increasing CD89. These results were not obtained in non-responders who instead increased the number of CD16 positive cells and CD64 positive cells. Interestingly, the monocytic expression of the inhibitory Fcg R (CD32b) was higher in good responders compared with non-responders at follow up.
Monocytic Fc receptor status is altered in early RA. Especially CD64 seems to be important. Successful response to standard anti-rheumatic treatment downregulates its expression.
2013. Vol. 72, no S3, A816-A816 p.