Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases

Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren sy...

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Main Authors:	Yamasaki, Yoshioki, Narain, Sonali, Hernandez, Liza, Barker, Tolga, Ikeda, Keigo, Segal, Mark S, Richards, Hanno B, Chan, Edward KL, Reeves, Westley H, Satoh, Minoru
Format:	Online
Language:	English
Published:	BioMed Central 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779422/

id	pubmed-1779422
recordtype	oai_dc
spelling	pubmed-17794222007-01-19 Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases Yamasaki, Yoshioki Narain, Sonali Hernandez, Liza Barker, Tolga Ikeda, Keigo Segal, Mark S Richards, Hanno B Chan, Edward KL Reeves, Westley H Satoh, Minoru Research Article Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset. BioMed Central 2006 2006-07-17 /pmc/articles/PMC1779422/ /pubmed/16846524 http://dx.doi.org/10.1186/ar2000 Text en Copyright © 2006 Yamasaki et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yamasaki, Yoshioki Narain, Sonali Hernandez, Liza Barker, Tolga Ikeda, Keigo Segal, Mark S Richards, Hanno B Chan, Edward KL Reeves, Westley H Satoh, Minoru
spellingShingle	Yamasaki, Yoshioki Narain, Sonali Hernandez, Liza Barker, Tolga Ikeda, Keigo Segal, Mark S Richards, Hanno B Chan, Edward KL Reeves, Westley H Satoh, Minoru Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
author_facet	Yamasaki, Yoshioki Narain, Sonali Hernandez, Liza Barker, Tolga Ikeda, Keigo Segal, Mark S Richards, Hanno B Chan, Edward KL Reeves, Westley H Satoh, Minoru
author_sort	Yamasaki, Yoshioki
title	Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
title_short	Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
title_full	Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
title_fullStr	Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
title_full_unstemmed	Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
title_sort	autoantibodies against the replication protein a complex in systemic lupus erythematosus and other autoimmune diseases
description	Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset.
publisher	BioMed Central
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779422/
_version_	1611393181099753472

Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases

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