Extended report
Decreased T cell precursor frequencies to Epstein-Barr virus
glycoprotein gp110 in peripheral blood correlate with disease
activity and severity in patients with rheumatoid arthritis
Eric Toussirota b, Daniel Wendlinga, Pierre Tiberghienb, Janos Lukac, Jean Roudierd
a Department
of Rheumatology, University Hospital J Minjoz, Bd A Fleming, 25030 F-Besançon, France, b Immunogenetic Laboratory, Blood Transfusion
Centre, 25000 F-Besançon, France, c Eastern Virginia Medical School,
Department of Pathology, Norfolk, Virginia, USA, d Immunorheumatology, INSERM E9940
Université de la Méditerranée, F-13005 Marseille, France
Correspondence to: Dr E Toussirot, Department of Rheumatology, University Hospital J Minjoz, Bd A Fleming, 25030 F-Besançon, France Email: eric.toussirot{at}ufc-chu.univ-fcomte.fr
Accepted for publication 17 January 2000
OBJECTIVES
Rheumatoid
arthritis (RA) is a chronic joint disease associated with certain
HLA-DR alleles expressing the QK/RRAA motif or shared epitope. The
Epstein-Barr virus (EBV) has been suspected to be a causative factor
for RA. The EBV gp110, a glycoprotein of the replicative cycle that
contains a copy of the shared epitope, constitutes an important target
in the immune control of EBV replication. This study evaluated the
specific T cell response to EBV gp110 in patients with RA expressing or
not the shared epitope and examined whether this immune cellular
response might be related to disease activity and severity.
METHODS25 patients
with RA were studied and compared with 25 healthy controls. Disease
activity was assessed by biochemical markers of inflammation
(erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)
levels). Disease severity was defined by extra-articular disease
(vasculitis, subcutaneous nodules, or other organ disease). The
frequencies of peripheral blood T cells specific for EBV gp110 and a
control protein (total protein extract from
Escherichia coli) were determined by direct
limiting dilution analysis without preliminary bulk culture.
RESULTSThe
gp110 precursor frequencies ranged from 0 to 20 × 10
6
in patients with RA and controls. The mean gp110 T cell precursor frequency was lower in patients with RA (SD 3.2 (4.4) × 10-6) than in healthy controls (4.1 (3.8) × 10-6) (p = 0.02). No difference was found for the control
protein (p = 0.09). Both shared epitope positive and negative patients with RA responded to gp110, without significant difference. A negative correlation between both ESR and CRP levels and the gp110 T
cell response was found (r = -0.71, p<0.0001 and r = -0.42, p = 0.038, respectively). Finally, patients with extra-articular disease
displayed the lowest immune cellular response to EBV gp110.
CONCLUSIONThese
results suggest that patients with RA have a decreased T cell
response to EBV gp110. Since gp110 is an important protein in the
control of EBV replication, this might lead to a poor control of EBV
infection, chronic exposure to other EBV antigens, and thus to a
chronic inflammatory response in patients with RA.
© 2000 by Annals of the Rheumatic Diseases
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