Chapter 15 - Antinuclear Antibodies: General Introduction

Abstract

Dating to the early description of the lupus erythematosus (LE) cell in systemic lupus erythematosus (SLE), over the ensuing half century techniques for antinuclear antibody (ANA) identification have significantly evolved. Today, the term ANA is commonly used to indicate both autoantibodies to nuclear and cytoplasmic antigens, and ANA are often used as biomarkers in patients who have demonstrated autoimmune reactions against self-antigens. Some ANA, such as anti-double-stranded deoxyribonucleic acid (ds-DNA), -Sm, -topoisomerase I (Scl-70), and -Jo-1, are well known for their highly specific association with certain systemic autoimmune rheumatic diseases (SARD) and this is especially true when these specific autoantibodies are present in high titer. Studies over the past two decades have led to the general thesis that certain ANA can be detected many years prior to the diagnosis of clinical disease. Thus, some ANA can be important biomarkers for the early detection of underlying SARD; however, the fact is that most individuals with a positive ANA test do not have SARD and will not develop SARD. There are some concerns that a trend of ANA ordering by clinicians is increasing in cases with little or no clinical implication for SARD. The consequence of this putative overuse is the criticism that such practice contributes to the higher costs in healthcare spending. This issue is compounded by recent reports of inaccuracy in ANA tests conducted in many large clinical diagnostic laboratories. The cause of inaccuracy has been attributed to the introduction of screening ANA enzyme-linked immunosorbent assay (ELISA), addressable laser bead immunoassays (ALBIA), and other multiplexed immunoassays as cost-saving technologies to supposedly streamline ANA detection. The standardization of ANA assays, reporting of test results, and the appropriate utilization of this information at the clinical interface is of utmost importance if ANA testing is to continue to be a clinical useful assay for clinicians and patients alike.