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


CONCLUSIONS
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.
Sicat
Jocelyn
J
Department of Rheumatology, Tufts-New England Medical Center, Boston, Massachusetts, USA.
Sutkowski
Natalie
N
Huber
Brigitte T
BT
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D020077:Endogenous Retroviruses / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000922:Immunotoxins / Q000032:analysis / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008558:Melphalan / Q000032:analysis / Q000276:immunology; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018089:Superantigens / Q000032:analysis / Q000276:immunology*; D005719:gamma-Globulins / Q000032:analysis / Q000276:immunology
D015415:Biomarkers; D004279:DNA, Viral; D000922:Immunotoxins; C045927:K-18 conjugate; D018089:Superantigens; D005719:gamma-Globulins; D008558:Melphalan