Extractable nuclear antigens

Abstract

ENAs are acidic macromolecules extracted from the saline soluble fractions of cells. Twenty different ENAs have been described to date. The antigens are derived from several different sources, and antibodies to these antigens can be detected by a number of different techniques. Antibodies to ENAs usually produce a speckled ANA pattern. The clinician, seeing such a result, will often pursue this by ordering an “ENA” to clarify which antigen-antibody system is responsible for the speckled ANA. Most often, clinical laboratories report results of hemagglutination assays giving the titers of agglutination with and without prior RNase digestion. Antibodies sensitive to RNase have been taken to be the equivalent of anti-RNP, the antibody associated with MCTD. Antibody not sensitive to RNase has often been equated with antibody to the Sm antigen associated with SLE. The failures and abuses of this nomenclature have been discussed in detail. Defining ENAs and the particular anti-ENA antibodies seen in individual patients is of value. From a clinical standpoint, defining these antigen-antibody systems may be helpful for diagnostic and prognostic purposes. From a more basic standpoint, understanding these antigenantibody systems may provide insights into the etiology and pathogenesis of CTDs. To date, only a few of the anti-ENA antibodies discussed above are available for routine clinical use. The extensive review of present information is briefly summarized below. The presence of antibody to RNP correlates with an overlap syndrome, MCTD, 3,12 though long-range studies have shown a progression of PSS-like features. 19,20 These patients, however, seem to have a favorable response to steroids. 3,12,19 Antibodies to Sm and MA are highly specific for SLE. 6–11 While antibodies to Sm may connote a more benign disease with less renal involvement, 8–10 antibodies to MA seem to point to more severe disease. 11 The presence of antibodies to PM-1, Mi, and Jo-1 are found mainly in patients with clinical findings of myositis. 24–28 However, they do not correlate with disease activity or severity. Antibodies to Scl-70 are highly specific for PSS. 29 Antibodies to SS-A (Ro) are found mainly in patients with SLE and/or the sicca complex, 39–43 and antibodies to SS-B (La or Ha) are present in patients with the sicca complex alone or in association with SLE. 37–39,41–43 Antibodies to Ro and/or La are directed to cytoplasmic constituents and would account for the presence of clinical SLE in patients with a negative ANA. 37,38,40 They may also be found in a more benign form of SLE. 39 Antibodies to RANA (SS-C) are found mainly in patients with RA or RA in combination with SS. 42,44 Thus, the patient with clinical symptoms of a CTD and a speckled ANA pattern or, in limited cases other ANA patterns or a negative ANA, should be evaluated for antibodies to ENA by the HA and ID. Such information can be useful in determining diagnosis and prognosis and expand our understanding of CTDs.