Down-regulation of leucocyte immunoglobulin-like receptor expression in the synovium of rheumatoid arthritis patients after treatment with disease-modifying anti-rheumatic drugs

Objectives. To compare the expression of leucocyte immunoglobulin-like receptors (LILRs) also known as ILTs and LIRs in rheumatoid arthritis (RA) synovial membrane before and after treatment with disease-modifying anti-rheumatic drugs (DMARDs) and investigate regulation of LILR-expression and functi...

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Bibliographic Details
Published in:	Rheumatology (Oxford, England) Vol. 46; no. 5; pp. 742 - 751
Main Authors:	Huynh, O. A., Hampartzoumian, T., Arm, J. P., Hunt, J., Borges, L., Ahern, M., Smith, M., Geczy, C. L., McNeil, H. P., Tedla, N.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-05-2007 Oxford Publishing Limited (England)
Subjects:	Aged Aged, 80 and over Antirheumatic Agents - pharmacology Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - immunology Biological and medical sciences Cells, Cultured Cohort Studies Diseases of the osteoarticular system Dose-Response Relationship, Drug Down-Regulation - drug effects Female Humans Inflammatory joint diseases Macrophage Activation Macrophages - drug effects Macrophages - metabolism Male Medical sciences Membrane Glycoproteins - metabolism Middle Aged Receptors, Fc - metabolism Receptors, Immunologic - metabolism Severity of Illness Index Synovial Membrane - immunology Leucocyte immunoglobulin-like receptors Rheumatoid arthritis Disease modifying anti-rheumatic drugs Human Immunopathology Chronic Immunoglobulins Treatment Synovial membrane Diseases of the osteoarticular system Autoimmune disease Inflammatory joint disease
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Summary:	Objectives. To compare the expression of leucocyte immunoglobulin-like receptors (LILRs) also known as ILTs and LIRs in rheumatoid arthritis (RA) synovial membrane before and after treatment with disease-modifying anti-rheumatic drugs (DMARDs) and investigate regulation of LILR-expression and function in vitro. Methods. A study was performed on serial synovial biopsies obtained from 10 RA patients before and after treatment with DMARDs. Expression of the activating LILRA2 (ILT1 or LIR-7) and inhibitory LILRB2 (ILT4 or LIR-2) and LILRB3 (ILT5 or LIR-3) was evaluated by immunohistochemical staining, and quantified by a validated scoring system. Peripheral blood mononuclear cells and in vitro derived macrophages were used to determine effects of DMARDs on expression and function of LILRs. Results. Abundant expression of LILRB2, B3 and A2 was found in synovial tissue of all patients before treatment. Number of inflammatory cells expressing both inhibitory and activating LILRs dramatically decreased in patients who responded to treatment, but remained high in those who did not. However, treatment of macrophages with DMARDs in vitro did not down-regulate LILR expression. On the other hand, reduction in LILR expression in RA synovia was associated with decreased inflammatory infiltrates in those who responded to treatment. Cross-linking of LILRA2 on macrophages caused substantial production of tumour necrosis factor (TNF-α) in a dose- and time-dependent manner that was strongly inhibited by dexamethasone. Conclusions. We show that expression of LILRs in RA synovium was significantly reduced only in patients who responded to treatment. However, clinical responses may not be due to direct effects of DMARDs on LILR expression but due to partial inhibition of LIRA2-mediated TNF-α production by steroids leading to suppression of inflammation.
ISSN:	1462-0324 1462-0332
DOI:	10.1093/rheumatology/kel405