The Rheumatoid Arthritis-Associated Autoantigen p68 Identified as Heavy Chain Binding Protein (BiP)

Journal/Book: Z Rheumatol 1999; 58 Suppl. 1: I/23 (FE 7). 1999;

Abstract: 1Rheumatol Charité Berlin; 2lnnogenetics Ghent Aim. p68 has been described as target of RA specific antibodies (ARD 54:355-60) and T cells (ARD 56:317-22). The aim was to further characterize and clone p68. Methods. p68 was isolated and subjected to Edman degradation and delayed matrix assisted laser desorption ionization-time of flight (DE-MALDI-TOF) mass spectrometry. Sensitivity and specificity of autoantibodies and autoreactive T cells were determined by immunoblotting and T cell proliferation assays respectively. Results. Edman sequencing of p68 identified the first l5 aminoacids (aa) as identical to the first 15 of the mature BiP. MALDI mass spectrometry also identified p68 as BiP (SwissProt P11021). 37 % of the total aa sequence of human BiP was covered by the detected peptide masses. 25/31 (80 %) of these matched with BiP. p68/BiP has been shown to be located in the endoplasmic reticulum in the nucleus and also on the cell surface under certain conditions. The molecular mass of p68/BiP is identical when analyzed on the same blot (72k). - Screening RA and control sera on western blots BiP-specific autoantibodies were detected in 199 out of 336 RA sera (59 %) and in 19 out of 183 sera from patients with other rheumatic diseases than RA (9 %) and in 1 out of 76 sera from healthy donors (1 %). Thus sensitivity of the anti-BiP response for RA was 59 % and specificity was 93 %. Screening RA and control PBMCs on T cell proliferation assays BiP-specific T cells were detected in 25 out of 38 (66 %) of RA patients and in none of 9 SLE patients and 10 healthy donors. ... le

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