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.
- AID, activation-induced cytidine deaminase
- ANA, antinuclear antibodies
- dUTP, deoxyuridine triphosphate
- o-JIA, oligoarticular juvenile idiopathic arthritis
- PCR, polymerase chain reaction
- RAG, recombination-activating gene
- SLE, systemic lupus erythematosus
Statistics from Altmetric.com
Published Online First 27 February 2006
Competing interests: None.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.