RESEARCH - Anti-RPA antibodies in SLE and other autoimmune diseases

[Guest guest]

Research article

Autoantibodies against the replication protein A complex in systemic lupus

erythematosus and other autoimmune diseases

Yoshioki Yamasaki1 , Sonali Narain1 , Liza 1 , Tolga Barker1 ,

Keigo Ikeda3 , Mark S Segal4 , Hanno B s1 ,2 , KL Chan3 ,

Westley H Reeves1 ,2 and Minoru Satoh1 ,2

1Division of Rheumatology and Clinical Immunology, Department of Medicine,

University of Florida, PO Box 100221, Gainesville, Florida, 32610, USA

2Department of Pathology, Immunology, and Laboratory Medicine, University of

Florida, PO Box 100221, Gainesville, Florida, 32610, USA

3Department of Oral Biology, University of Florida, PO Box 100424,

Gainesville, Florida, 32610, USA

4Division of Nephrology, Department of Medicine, University of Florida, PO

Box 100221, Gainesville, Florida, 32610, USA

Arthritis Research & Therapy 2006, 8:R111

Published 17 July 2006

Abstract

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.

http://arthritis-research.com/content/8/4/R111/abstract

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org