Expression of human endogenous retrovirus HERV-K18 superantigen is elevated in juvenile rheumatoid arthritis

• Published in: Journal of rheumatology 2005-09, Vol.32 (9), p.1821-1831
• Main Authors: SICAT, Jocelyn, SUTKOWSKI, Natalie, HUBER, Brigitte T
• Format: Article
• Language: English
• Subjects: Adolescent; Arthritis, Juvenile - blood; Arthritis, Juvenile - immunology; Biological and medical sciences; Biomarkers - analysis; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Diseases of the osteoarticular system; DNA, Viral - analysis; Endogenous Retroviruses - immunology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; gamma-Globulins - analysis; gamma-Globulins - immunology; Humans; Immunotoxins - analysis; Immunotoxins - immunology; Inflammatory joint diseases; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Male; Medical sciences; Melphalan - analysis; Melphalan - immunology; Probability; Prognosis; Reference Values; Reverse Transcriptase Polymerase Chain Reaction - methods; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensitivity and Specificity; Severity of Illness Index; Superantigens - analysis; Superantigens - immunology
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To investigate the presence of a host-encoded superantigen as possible etiologic factor in pediatric rheumatic disease. We measured the expression and the ability of interferon-alpha (IFN-alpha) to induce the human endogenous retrovirus HERV-K18 superantigen in juvenile rheumatoid arthritis (JRA) and pediatric systemic lupus erythematosus (SLE). METHODS: Expression levels of HERV-K18 were measured in peripheral blood or synovial fluid mononuclear cells (SFMC) from 13 patients with JRA, 11 pediatric SLE patients, and 24 healthy controls, by semiquantitative reverse transcription-polymerase chain reaction, comparing 18S ribosomal transcripts as endogenous standard. IFN-alpha induction was tested by pretreatment of samples with 2000 U/ml. RESULTS: HERV-K18 expression was significantly elevated in peripheral blood from patients with JRA (mean ratio of HERV-K18 to 18S ribosomal transcripts 2.456, SD 2.122; p = 0.014), but not patients with SLE (mean 0.997, SD 0.579; p = 0.258), compared to controls (mean 0.749, SD 0.598). HERV-K18 transcripts were detected in SFMC of 7/7 JRA patients. IFN-alpha induced HERV-K18 strongly in JRA (mean fold induction = 8.934, SD 15.556) and controls (mean 8.270, SD 6.609), but weakly in SLE (mean 2.432, SD 2.219; p = 0.009). HERV-K18 levels were found to be independent of previously determined modifiers of expression, including Epstein-Barr virus infection, IFN-alpha levels, or the percentage of B cells in peripheral blood. CONCLUSION: HERV-K18 superantigen levels were elevated in JRA patients, but not pediatric patients with SLE, suggesting a possible mechanism for autoimmunity in the former group by superantigen stimulation of autoreactive T cells.