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9G4 expression on autoantibodies to citrullinated peptides in patients with early inflammatory arthritis and established rheumatoid arthritis
  1. Rita A Moura1,
  2. Inmaculada de la Torre2,
  3. Maria J Leandro3,
  4. Jonathan C W Edwards3,
  5. João E Fonseca1,4,
  6. Geraldine Cambridge3
  1. 1Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal
  2. 2Rheumatology Department, Gregorio Marañón Hospital, Madrid, Spain
  3. 3Centre for Rheumatology, Division of Medicine, University College London, London, UK
  4. 4Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon, Portugal

Abstract

Background The rat monoclonal antibody 9G4 recognises VH4-34-encoded proteins, enabling the identification of inherently autoreactive B cells. In rheumatoid arthritis (RA), evidence for a humoral immune response encoded by VH4-34 gene has been described in the synovial membrane and within hybridomas derived from rheumatoid synovial tissue. The authors have recently described an expansion of circulating 9G4+ plasmablasts in patients with active RA.

Objectives The aim of this study was to determine whether 9G4+ was expressed on autoantibodies commonly associated with RA.

Materials and methods Serum from 27 patients with established RA and 46 polyarthritis patients (<6 weeks duration) of whom 23/46 were subsequently diagnosed with RA (Early RA, ERA) and 23/46 with other arthritis (early non-RA, ENRA) was studied. 9G4 expression on anti-CCP, antitetanus toxoid (TT), pneumococcal capsular polysaccharide (PCP) antibodies and total serum IgG and IgM was measured by ELISA.

Results 23/27 patients with established RA had anti-CCP antibodies, in which eight expressed 9G4. All were positive for both IgM and IgG anti-CCP. Levels of 9G4 expression correlated more closely with IgM than IgG-CCP. In ERA group, 15/23 patients had anti-CCP and 4/23 had 9G4+ anti-CCP. All 4 patients had both IgM and IgG anti-CCP. In ENRA, only one patient had 9G4+ IgM anti-CCP, albeit at low titre. 9G4 was not expressed on TT or PCP antibodies.

Conclusions The authors describe the use of the VH4-34 heavy chain gene by autoantibodies to citrullinated peptides early after RA onset. In established RA, usage of VH4-34 by anti-CCP antibodies increased with increasing titre, particularly in IgM-CCP. Therefore, it is possible that the expansion of CCP-specific B cell clones may be due to robust expansion of un-switched B cell clones, possibly including or analogous to those in the splenic marginal zone. This is the first description of the use of the VH4-34 heavy chain gene by autoantibodies to citrullinated peptides. 9G4 expression was largely confined to CCP antibodies from patients with RA.

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