CCR4, CCR5 expression and macrophage inflammatory protein-1 alpha levels in rheumatoid arthritis

Abstract EN

Objective : to characterize the expression profile of chemokine receptors CCR5, CCR4 on CD4 T lymphocytes and to measure levels of the chemokine MIP-1α in peripheral blood and synovial fluid of patients with rheumatoid arthritis, correlating them to disease activity score, CRP titer and synovial fluid levels of IFN- in a trial to explore the potential involvement of the chemokine system in rheumatoid arthritis.

Methodology : the study included 15 female patients with rheumatoid arthritis (RA) diagnosed according to the American College of Rheumatology Criteria.

All having active disease with knee effusion and 7 females with traumatic knee effusion served as the control group.

They were all attending the outpatient clinics of Rheumatology & Rehabilitation and Internal Medicine departments of Ain Shams University Hospitals.

They were subjected to history taking, thorough clinical examination, and assessment of disease activity using modified Disease Activity Score (DAS), laboratory investigations mainly: measurement of CRP titer, plasma and synovial fluid levels of macrophage inflammatory protein-1 (MIP-1α), synovial fluid levels of interferon gamma (IFN-α), expression percentage of CCR5, CCR4 on CD4 T lymphocytes of peripheral blood (PB) and synovial fluid (SF).

Results : MIP-1α levels were highly significantly increased in RA patients when compared to controls in both peripheral blood (PB) (t = 13.7) and synovial fluid (SF) (t = 8.8).

Similarly CCR5+ CD4 T lymphocytes percentage ( %) expression showed high significant increase in RA patients versus controls in PB and SF (t = 4.9, t = 11.7) respectively.

On the contrary CCR4+ CD4 T lymphocytes % expression showed no significant difference between both groups whether in PB (t = 1.2) or SF (t = 1.3).

SF levels of IFN-γ were highly significantly increased in patients compared to controls (t = 6.3).

On comparing PB and SF in RA patients, there was high significant increase in MIP-1α levels, CCR5+ CD4 T lymphocytes % expression in SF versus PB (t = 12.5, t = 15.7) respectively.

While % expression of CCR4+ CD4 T lymphocytes showed high significant increase in PB compared to synovial fluid (t = 16.9).

SF levels of MIP-1α in RA patients showed highly significant positive correlations with DAS (r=0.74), CRP titer (r = 0.73) and SF IFN-γ levels (r = 0.78) with no significant correlation to SF CCR4+ CD4 T lymphocytes % expression (r= 0.28).

Among RA patients, SF CCR5+ CD4 T lymphocytes % expression was significantly correlated with DAS (r=0.57), CRP titer (r = 0.58), SF leucocytic count (r = 0.54), and highly significantly correlated with SF MIP-1α levels (r = 0.65) and SF IFN-γlevels (r = 0.79).

On the other hand SF CCR4+ CD4 T lymphocytes % expression showed no significant correlation with DAS (r = 0.11), CRP titer (r = 0.22) or SF IFN-γ levels (r=0.29) in RA patients.

Conclusion : CCR5+ CD4 T lymphocytes accumulate in the joints of patients with rheumatoid arthritis under the influence of high synovial fluid levels of MIP-1α (the ligand of CCR5).

So the interaction between CCR5 and MIP-1αmay be critical in RA and their significant correlation with disease activity score and CRP titer ; the marker of inflammation may indicate their contribution to the inflammatory process in RA.

The type 1 T helper cell bias in RA synovial fluid may be associated with the presence of CCR5 expressing lymphocytes.

MIP-1α and CCR5 may be important therapeutic targets in RA.