Antibodies to the endoplasmic reticulum-resident chaperones calnexin, BiP and Grp94 in patients with rheumatoid arthritis and systemic lupus erythematosus

被引:38
作者
Weber, Christian K. [3 ]
Haslbeck, Martin [4 ]
Englbrecht, Matthias [1 ,2 ]
Sehnert, Bettina [1 ,2 ,3 ]
Mielenz, Dirk [5 ]
Graef, Daniela [1 ,2 ]
Distler, Joerg H. [1 ,2 ]
Mueller, Ruediger B. [1 ,2 ,6 ]
Burkhardt, Harald [7 ]
Schett, Georg [1 ,2 ]
Voll, Reinhard E. [1 ,2 ,3 ]
Fuernrohr, Barbara G. [1 ,2 ,3 ]
机构
[1] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany
[3] Univ Erlangen Nurnberg, IZKF Res Grp 2, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany
[4] Tech Univ Munich, Dept Chem, Munich, Germany
[5] Univ Erlangen Nurnberg, Dept Internal Med 3, Div Mol Immunol, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany
[6] Kantonsspital St Gallen, Dept Rheumatol, St Gallen, Switzerland
[7] Goethe Univ Frankfurt, Div Rheumatol, Dept Internal Med 2, Frankfurt, Germany
关键词
Rheumatoid arthritis; Systemic lupus erythematosus; Chaperone; Heat shock protein; Autoantibodies; ELISA; Calnexin; Grp94; BiP; HEAT-SHOCK PROTEINS; ANTIGEN PRESENTATION; REVISED CRITERIA; MOLECULAR CHAPERONES; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSE; CLASSIFICATION; COLLAGEN; DISEASES; PEPTIDE;
D O I
10.1093/rheumatology/keq272
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Methods. Sera from healthy donors, from early RA patients with two follow-up samples, patients with SLE, SSc and IBD were collected and analysed for anti-ER chaperone antibodies. Detection of serum IgG antibodies against immunoglobulin heavy chain binding protein (BiP), glucose-regulated protein 94 (Grp94) and calnexin was carried out using ELISA. The specificity of sera positive for individual ER chaperones was confirmed by immunoblotting. Statistical analysis was performed using Welch's t-test, Mann-Whitney U-test, partial correlation and Pearson's correlation. Results. In patients with RA and SLE, autoantibody titres against BiP, Grp94 and calnexin were significantly higher than those in healthy controls. These autoantibodies were detectable in patients with early RA and titres remained stable for at least 6-12 months. Also several SSc and IBD patients exhibited autoantibodies against these ER chaperones; however, titres and frequencies were lower than in RA or SLE patients. Furthermore, anti-calnexin antibodies correlated significantly with the presence of BiP and Grp94 autoantibodies in patients with RA and SLE. Conclusion. Calnexin and Grp94 were identified as novel autoantigens in RA and calnexin in SLE. Since calnexin, Grp94 and BiP are ER-resident proteins of eukaryotic cells, our data suggest that autoantibody generation against ER chaperones is independent of initial exposure to the corresponding bacterial chaperones; rather, ER chaperones may represent genuine autoantigens.
引用
收藏
页码:2255 / 2263
页数:9
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