Increased Serum Levels of Anti-Carbamylated 78-kDa Glucose-Regulated Protein Antibody in Patients with Rheumatoid Arthritis.

Hui-Chun Yu,Hsien-Bin Huang,Ning-Sheng Lai,Malcolm Koo,Ming-Chi Lu,Pei-Hsuan Lai

doi:10.3390/ijms17091510

Abstract

The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay. No differences in serum titers of anti-GRP78 antibody in patients with RA, SLE, or pSS compared with the controls were observed. Serum levels of anti-carGRP78 antibody in patients with RA, but not SLE or pSS, were significantly higher compared with the controls (OD405 0.15 ± 0.08 versus 0.11 ± 0.03, p = 0.033). There was a positive correlation between the serum levels of anti-GRP78 antibody, but not anti-CarGRP78 antibody, with the levels of anti-CCP antibody in patients with RA. Both anti-GRP78 and anti-carGRP78 antibodies failed to correlate with C-reactive protein levels in patients with RA. In conclusion, we demonstrated the presence of anti-CarGRP78 antibody in patients with RA. In addition, the serum titer of anti-CarGRP78 antibody was significantly elevated in patients with RA compared with the controls. Anti-CarGRP78 antibody could also be detected in patients with SLE or pSS.

Highlights

The 78 kDa glucose-regulated protein (GRP78), known as binding immunoglobulin protein (BiP), has been shown to be an important autoantigen for rheumatoid arthritis (RA)
We found that GRP78 was citrullinated and became recognizable by Anti-citrullinated protein antibody (ACPA), and ACPAs could directly stimulate monocytes to secrete tumor necrosis factor α (TNF-α) via binding to citGRP78 [3]
We found that there were no significant correlations between the serum level of anti-GRP78 antibody or anti-CarGRP78 and the CRP levels in patients with RA (Figure 4)

Summary

Introduction

The 78 kDa glucose-regulated protein (GRP78), known as binding immunoglobulin protein (BiP), has been shown to be an important autoantigen for rheumatoid arthritis (RA). GRP78 could stimulate the proliferation of synovial T cells from patients with RA [1]. Anti-GRP78 antibody can be found in the serum from patients both after and before their diagnosis of RA [2]. Anti-citrullinated protein antibody (ACPA) is known to be a very specific diagnostic marker for RA. We found that GRP78 was citrullinated (citGRP78) and became recognizable by ACPAs, and ACPAs could directly stimulate monocytes to secrete tumor necrosis factor α (TNF-α) via binding to citGRP78 [3]. Anti-citGRP78 antibody was widely detected in serum from patients

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Conclusion