[Frontiers in Bioscience 14, 3733-3739, January 1, 2009]

Autoantibody to NA14 is an independent marker primarily for Sjögren's syndrome

Kazuhisa Nozawa1, Keigo Ikeda2,3, Minoru Satoh4, Westley H. Reeves4, Carol M. Stewart5, Yueh-Chun Li6, Tim J. Yen6, Rosa M. Rios7, Kenji Takamori1, Hideoki Ogawa1, Iwao Sekigawa1, Yoshinari Takasaki2, Edward K.L. Chan3

1 Department of Rheumatology and Internal Medicine, Juntendo University Urayasu hospital, Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan, 2Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan; 3Department of Oral Biology, University of Florida, Gainesville, FL, 4Division of Rheumatology and Clinical Immunology, Department of Medicine, and Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 5Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL; 6Fox Chase Cancer Center, Philadelphia, PA, 7Centro Andaluz de Biologia Molecular y Medicina Regenerativa, Edif. CABIMER. Avda. Americo Vespucio, Sevilla, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods
3.1. Human sera
3.2. Recombinant NA14 protein
3.3. Enzyme-linked immunosorbent assay
3.4. Immunoblotting
4. Results
5. Discussion
5.1. Diseases specificity of anti-NA14 antibody
5.2. Coiled-coil proteins elicit autoantibodies production
5.3. Pathogenesis of NA14 in primary SS
6. Acknowledgement
7. References

1. ABSTRACT

Nuclear Autoantigen of 14 kDa (NA14) was originally identified using the serum of a Sjögren's syndrome (SS) patient as probe in screening a human testis cDNA expression library. To date there is no report in the systematic analysis of the prevalence of autoantibodies to NA14. In this study, anti-NA14 was determined in several rheumatic diseases from independent cohorts in the US and Japan. The prevalence of anti-NA14 were 18/132 (13.6%) in primary SS, 0/50 (0%) secondary SS, 2/100 (2%) SLE, 1/43 (2.3%) scleroderma, 0/54 (0%) rheumatoid arthritis, 1/29 (3.4%) polymyositis/dermatomyositis, and 0/58 (0%) normal healthy controls. The frequencies of anti-NA14 positive sera in primary SS are statistically greater than normal healthy controls (p=0.006), secondary SS (p=0.044), and other rheumatic diseases. Furthermore, among 11 anti-NA14 positive primary SS sera, 4/11 (36.3%) sera were negative for both anti-SS-A/Ro and SS-B/La antibodies. Thus anti-NA14 autoantibodies may be useful for the discrimination of primary versus secondary SS and serve as a diagnostic marker for primary SS especially in seronegative (anti-SS-A/Ro and anti-SS-B/La antibodies negative) patients with SS.