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ANTINUCLEAR ANTIBODIES

A characteristic feature of many systemic autoimmune diseases is the presence of  antinuclear antibodies (antinuclear antibodies). These autoreactive antibodies, however, are not limited to nuclear antigens and may target extranuclear structures in the cytoplasm, nucleus, and nucleolus; thus, the term antinuclear antibodies is often broadened to include the entire spectrum of antigenic specificities antinuclear antibodies, ANA, antinuclear antibody. In most cases, autoantibodies bind proteins, but DNA, RNA, and lipids can also be autoantigenic. Antinuclear antibodies have been the subject of 

Antinuclear antibodies are clinically important because each systemic autoimmune disease has a characteristic ANA spectrum. Although some antinuclear antibodies can be detected in more than one disease, certain antibody specificities are associated almost exclusively with a particular disease and serve therefore as useful diagnostic markers. For example, anti-Smith antigen (anti-Sm) and anti-double-stranded DNA antibodies (anti-dsDNA) are rarely detected in any condition other than systemic lupus erythematosus (SLE), and the presence of these antibodies is included in the diagnostic criteria of the disorder. Some antinuclear antibodies also help identify subsets of patients within a diagnostic category: anti-Jo-1 and other anti-transfer RNA (anti-tRNA) synthetase autoantibodies are present in a subgroup of patients with polymyositis who have interstitial lung involvement and a poor prognosis. Anti-dsDNA antibodies and

DETECTION OF ANTINUCLEAR ANTIBODIES

The indirect immunofluorescence assay for antinuclear antibodies (FANA) is a commonly used test for antinuclear antibodies and is usually the initial screening test. The use of cryopreserved tissues or organs as substrates has largely been superseded by tissue culture cell lines, such as the human laryngeal epithelioma cancer cell line (Hep-2 cells). Such cell lines are more efficient substrates, have large nuclei and nucleoli, have a higher frequency of certain antigens, and are

Antinuclear antibodies are common in patients with systemic rheumatic diseases such as systemic lupus erythematosus (SLE), scleroderma (SSc), Sjogren's syndrome, and inflammatory muscle diseases. Each of these diseases has a distinct autoantibody profile that may have diagnostic and, in some circumstances, prognostic value. For example, anti-DNA topoisomerase I (Scl-70), anti-U3 ribonucleoprotein (anti-U3-RNP), and anti-RNA polymerase I, II, and III antibodies are associated with diffuse cutaneous scleroderma and more severe systemic disease, whereas anticentromere antibodies are typically associated with the limited form of scleroderma. The autoantibodies associated with polymyositis/dermatomyositis (PM-DM) or PM-DM overlap syndromes include the myositis-specific autoantibodies (MSAs), which are detected almost exclusively in patients with inflammatory myositis, and these antibodies may be useful for diagnosis and patient classification.

Patients with certain systemic rheumatic diseases often produce multiple autoantibodies with different specificities. For example, patients with SLE produce an average of three distinct autoantibodies. Some antinuclear antibodies tend to occur consistently together, such as antibodies to histones and dsDNA, and antibodies against the Ro and La antigens. Such linked

AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS, MIXED CONNECTIVE TISSUE DISEASE, AND SJOGREN'S SYNDROME

Antinuclear antibody production is ubiquitous in patients with SLE. When tissue culture cell lines are used, 99% of SLE patients have a positive FANA, often in high titer. The antibody response is heterogeneous and polyclonal; a typical patient has an average of three autoantibody specificities. The prevalence of autoantibodies varies over a wide range. Autoantibodies

Anti-Ro and Anti-La antibodies are present in most patients with primary Sjogren's syndrome, occurring in more than 90% of such patients and their presence is one of the main criteria for disease classification. The Ro/SSA and La/SSB autoantibodies in Sjogren's syndrome are

ANTINUCLEAR ANTIBODIES AND THE UNDERLYING PATHOGENESIS OF CONNECTIVE TISSUE DISEASES

Most of the autoantibodies in patients with connective tissue diseases do not likely cause direct tissue injury, with the possible exception of anti-dsDNA and anti-Ro antibodies. The study of autoantibodies and the structure and function of their antigenic targets has produced indirect evidence that autoantibodies are causally linked with these diseases, and that they are not simply the product of B-lymphocyte overactivation, which is invariably present. First, and perhaps most important, subtypes of antinuclear antibodies are specific for the individual connective tissue diseases. Secondly, antinuclear antibodies apparently arise secondary to direct autoantigenic drive. The following observations support this notion: antinuclear antibodies often