INVERSION OF MHC-CLASS II TRANSCRIPTION LEVELS IN JOINTS OF CHILDREN WITH EOPA-JCA J

INVERSION OF MHC-CLASS II TRANSCRIPTION LEVELS IN JOINTS OF CHILDREN WITH EOPA-JCA
J. Peter Haas(1), Carola Frank(1), Renate Haefner(2), Stefany Fernandez(1), Ralf Wassmuth(3) and Hans Ruder(2).
(1) Children´s Hospital, University of Erlangen-Nuremberg, Germany, (2) Children´s Rheumatology Hospital, Garmisch-Partenkirchen, Germany, (3) Institute for clinical Immunology and Rheumatology, University of Erlangen, Germany.

Purpose: Susceptibility to early onset pauciarticular (EOPA) JCA was shown to be associated with a sequence-motif located in the HLA-DQ a-chain (HLA-DQA1*0401, *0501, *0601). The susceptible DQA1 alleles carry a Y-box mutation in their proximal promotor which has been demonstrated to be effective in gene transcription. The aim of our study was to investigate expression of MHC-class II in different forms of arthritis.
Materials & Methods: Semiquantitative measurement of MHC-class II transcripts (HLA-DRA, HLA DQA1) was performed with a RT-PCR technique using RNA prepared from peripheral mononuclear cells (PBMC) of healthy donors (n = 4), EOPA-JCA patients (n = 7), systemic JCA (n = 3) and patients with acute forms of arthritis (n = 2). In addition RNA from intraarticular mononuclear cells (IAMC) derived from affected joints (n = 12) were analyzed. Competitive PCR was then performed using internal standards for HLA-DRA and -DQA1. Typing for HLA-DQA1 alleles and the Y-box mutation was done by PCR/Oligotyping of genomic DNA.
Results: Most of the EOPA-JCA patients (86%) carry the mutated DQA1 Y-box, compared to 34% of healthy controls found in an earlier study. Transcription-levels of HLA-DRA and -DQA1 in PBMC were observed with similar ratios in patients as well as in healthy controls. HLA-DRA showed a 5 to 10 fold higher transcription rate as compared to -DQA1. Analyses in IAMC showed essentially the same ratio as in PBMC in all patients except EOPA-JCA. IAMC from EOPA-JCA patients showed an intraarticular upregulation of MHC-class II mRNA levels with a preferential expression of HLA-DQA1 resulting in an inverted HLA-DRA/DQA1 ratio.
Conclusion: There is evidence for a local imbalance of MHC-class II expression in the affected joints of EOPA-JCA patients. The findings support our hypothesis oof a direct involvment of MHC-class II antigens in the pathogenesis of EOPA-JCA.