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OP0120 Specific Identification of Anti-Citrullinated Glucose-6-Phospate Isomerase Peptide (CCG) Antibodies Associated with HLA-DRB1 SE and Disease Activity in Patients with RA
  1. N. Umeda1,
  2. I. Matsumoto2,
  3. A. Inoue1,
  4. Y. Tanaka1,
  5. Y. Kondo1,
  6. H. Tsuboi1,
  7. T. Suzuki1,
  8. N. Tsuchiya3,
  9. T. Sumida1
  1. 1Department of Internal Medicine, Faculty of Medicine
  2. 2Division of Clinical Immunology, Major of Advanced
  3. 3Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, UNIVERSITY OF TSUKUBA, Tsukuba-city, Japan

Abstract

Background Anti-citrullinated protein antibodies (Abs) (ACPA) are identified as a hallmark of diagnosis and disease progression in sera of patients with RA. Although several ACPA targeting citrullinated fibrinogen, collagen type II, a-enolase and vimentin have been confirmed, their pathogenic role are still mostly elusive due to the lack of association to disease activity. Anti-glucose-6-phosphate isomerase (GPI) Abs is confirmed as arthritogenic in mouse model, and only few patients with RA possessed them, however, anti-cyclic citrullinated GPI peptide (CCG) Abs have not been characterized.

Objectives To identify and characterize anti-CCG Abs in patients with RA.

Methods 1) Nine arginine-bearing peptide sequences in human GPI were selected and cyclic citrullinated GPI peptides (CCG-1∼-9) were constructed. Five unmodified GPI peptides were also synthesized (G-1, -2, -3, -4 and -7). Samples were obtained from patients with RA (n=208), SLE (n=101), Sjögren’s syndrome (SS; n=101), and from healthy control subjects (n=174). Abs against CCG-1∼-9 and G-1, -2, -3, -4, -7 were measured by ELISA, and anti-citrullinated a-enolase-1 (CEP-1), and anti-CCP Abs were also examined.

2) Patients with RA were genotyped for HLA-DRB1. The numbers of shared epitope (SE) alleles were counted and compared with positivity of anti-CCG Abs.

3) The levels of auto-Abs were compared before and after six month treatment with TNF antagonists in 58 RA patients (infliximab, n=41, etanercept, n=15, adalimumab, n=2).

Results 1) Anti-CCG-2, -4 and -7 Abs were detected in 25.5%, 33.2% and 37.0% patients with RA, respectively. These Abs were specific for RA (specificity, 98.1% ∼ 99.7%). Abs against five unmodified GPI peptides were detected only 0% ∼ 3.8% patients with RA. Altogether, 44.2% and 86.1% of RA sera were positive for anti-CEP-1 and -CCP Abs. The levels of anti-CCG-2, -4 and -7 Abs were correlated with that of anti-CCP and anti-CEP-1 Abs.

2) Anti-CCG-2, -4 and -7 Abs were significantly correlated with the presence of HLA-DRB1 SE alleles (P<0.01, P<0.05 and P<0.001, respectively).

3) Treatment with TNF antagonists significantly reduced the levels of anti-CCG-2 and -7 Abs (P<0.001, P<0.05, respectively), but not of anti-CEP-1 Abs.

Conclusions This is the first report documenting the presence of anti-CCG-1∼-9 Abs in patients with RA. Anti-CCG-2 and -7 Abs could be considered as markers for the diagnosis of RA and its disease activity.

Disclosure of Interest None Declared

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