Expression of Fcγ and complement receptors on peripheral blood monocytes in systemic lupus erythematosus and rheumatoid arthritis

• Published in: Rheumatology (Oxford, England) Vol. 43; no. 5; pp. 547 - 554
• Main Authors: Hepburn, A. L., Mason, J. C., Davies, K. A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2004
• Subjects: Biological and medical sciences; Complement receptor; Diseases of the osteoarticular system; Fcγ receptor; Inflammatory joint diseases; Medical sciences; Monocyte; Rheumatoid arthritis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; SLE; Immunopathology; Connective tissue disease; Complement receptor; Skin disease; Monocyte; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Complement; SLE; Blood; Chronic; Systemic lupus erythematosus; Rheumatoid arthritis; Systemic disease; Fcy receptor
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keh112

Objectives. Fcaγ and complement receptors play an important role in the interaction between immune complexes (IC) and monocytes/macrophages. Recent work has demonstrated that their relative expression on these cells may be modified by cytokines, including TNF-α and IL-4. Furthermore, cytokines may alter the expression of adhesion molecules such as ICAM-1. However, little data exist on the in vivo expression of specific Fcγ and complement receptors in systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), two diseases in which IC are important in pathogenesis. Methods. Venous blood was obtained from 30 patients with SLE, 25 with RA and 25 healthy controls. Monocyte phenotype was determined by flow cytometric analysis of whole blood samples, with selective gating using forward and side scatter signals. Surface expression of Fcγ receptors RI (CD64), RII (CD32) and RIII (CD16), complement receptors CR1 (CD35) and CR3 (CD11b/CD18), and adhesion molecules ICAM-1 (CD54) and CD11a (LFA-1) was determined. The effects of disease activity and corticosteroid therapy on the expression of these molecules were also examined. Results. The expression of FcγRII was reduced on monocytes from patients with SLE compared with healthy controls and patients with RA (P = 0.002). This did not correlate with disease activity using conventional indices [SLEDAI (SLE disease activity index), C3/C4 levels and anti-double-stranded DNA antibody titres], and was independent of prednisolone therapy. There was no significant difference in FcγRI or RIII expression on SLE monocytes compared with healthy controls. In contrast, the expression of FcγRIII was increased on RA monocytes (P = 0.01), this being highest in patients with active disease. The proportion of FcγRIII-positive monocytes was also increased in RA, and prednisolone therapy was associated with a lower proportion of FcγRIII-positive cells. An increase in CR3 expression was seen on RA monocytes (P = 0.002), whilst CR1 was increased on monocytes from patients with active SLE or active RA. ICAM-1 expression was reduced on monocytes from patients with SLE (P = 0.002), although high-dose prednisolone therapy was associated with the lowest level of surface ICAM-1 on monocytes. Conclusions. Peripheral blood monocytes from patients with SLE or RA display significantly altered phenotypes compared with those from healthy controls. The observed reduction in SLE of FcγRII may represent a mechanism by which monocytes are protected from IC-mediated activation. Prednisolone therapy and disease activity had little effect on phagocytic receptor expression. The observed changes may reflect the different cytokine profiles seen in SLE and RA.