C Faber1, H Morbach, S K Singh, H J Girschick. 1. Section of Paediatric Rheumatology and Osteology, Children's Hospital, University of Würzburg, Josef Schneider Str 2, D-97080 Würzburg, Germany.
Abstract
BACKGROUND: Re-expression of the recombination-activating genes (RAG) in peripheral B cells may be relevant in the development of autoreactive antibodies in autoimmune diseases. The presence of antinuclear antibodies (ANA) as a hallmark of oligoarticular juvenile idiopathic arthritis (o-JIA, early-onset type) indicates a breakdown in immunological tolerance. AIM: To examine the expression of RAG genes in peripheral blood mature B lymphocytes in patients with o-JIA. METHODS: 777 memory B cells from peripheral blood, CD19+ CD27+ CD5+ or CD19+ CD27+ CD5-, isolated from three ANA+ children with o-JIA and three healthy age-matched children, were examined for the expression of RAG1 and RAG2 mRNA. mRNA transcripts of activation-induced cytidine deaminase and immunoglobulin G were searched to further determine their developmental stage. RESULTS: mRNA was present for any of the two RAG genes in the B cells of children with JIA and controls. However, the predominance of RAG1 or RAG2 was different. A significantly decreased frequency of RAG2-expressing memory B cells in both CD5+ and CD5- populations was noted in children with JIA (p<0.001), whereas the number of RAG1-expressing B cells was slightly increased. The coordinate expression of both the RAG genes was a rare event, similar in the CD5+ populations (1% in controls, 2% in children with JIA), but different among the CD5- compartments (5% v 0%; p<0.01). CONCLUSION: These results argue for a reduced coordinate RAG expression in the peripheral CD5- memory B cells of patients with o-JIA. Thus, it was hypothesised that impaired receptor revision contributes to autoimmune pathogenesis in JIA.
BACKGROUND: Re-expression of the recombination-activating genes (RAG) in peripheral B cells may be relevant in the development of autoreactive antibodies in autoimmune diseases. The presence of antinuclear antibodies (ANA) as a hallmark of oligoarticular juvenile idiopathic arthritis (o-JIA, early-onset type) indicates a breakdown in immunological tolerance. AIM: To examine the expression of RAG genes in peripheral blood mature B lymphocytes in patients with o-JIA. METHODS: 777 memory B cells from peripheral blood, CD19+ CD27+ CD5+ or CD19+ CD27+ CD5-, isolated from three ANA+ children with o-JIA and three healthy age-matched children, were examined for the expression of RAG1 and RAG2 mRNA. mRNA transcripts of activation-induced cytidine deaminase and immunoglobulin G were searched to further determine their developmental stage. RESULTS: mRNA was present for any of the two RAG genes in the B cells of children with JIA and controls. However, the predominance of RAG1 or RAG2 was different. A significantly decreased frequency of RAG2-expressing memory B cells in both CD5+ and CD5- populations was noted in children with JIA (p<0.001), whereas the number of RAG1-expressing B cells was slightly increased. The coordinate expression of both the RAG genes was a rare event, similar in the CD5+ populations (1% in controls, 2% in children with JIA), but different among the CD5- compartments (5% v 0%; p<0.01). CONCLUSION: These results argue for a reduced coordinate RAG expression in the peripheral CD5- memory B cells of patients with o-JIA. Thus, it was hypothesised that impaired receptor revision contributes to autoimmune pathogenesis in JIA.
Authors: Ross E Petty; Taunton R Southwood; Prudence Manners; John Baum; David N Glass; Jose Goldenberg; Xiaohu He; Jose Maldonado-Cocco; Javier Orozco-Alcala; Anne-Marie Prieur; Maria E Suarez-Almazor; Patricia Woo Journal: J Rheumatol Date: 2004-02 Impact factor: 4.666
Authors: K Schwarz; G H Gauss; L Ludwig; U Pannicke; Z Li; D Lindner; W Friedrich; R A Seger; T E Hansen-Hagge; S Desiderio; M R Lieber; C R Bartram Journal: Science Date: 1996-10-04 Impact factor: 47.728
Authors: Y Shinkai; G Rathbun; K P Lam; E M Oltz; V Stewart; M Mendelsohn; J Charron; M Datta; F Young; A M Stall Journal: Cell Date: 1992-03-06 Impact factor: 41.582