Diversity and origin of rheumatologic autoantibodies

Abstract

A hallmark of sera from patients with systemic rheumatic diseases is the presence of circulating autoantibodies directed against nuclear antigens. The identification of the antigens binding to these antibodies has provided the cell biologist and the immunologist with important tools to study cell structure, cell function, and the processes underlying the immune response. Through the elucidation of autoantibody specificities, the clinician has been provided with a better appreciation of the diagnostic and prognostic significance of autoantibodies. Many autoantigens, including those directed against components in the nuclear matrix, chromosomes, Golgi apparatus, and other intracellular antigens, are not yet characterized nor is their clinical significance established. The mechanisms leading to the breakdown of tolerance and the appearance of autoantibodies are not fully understood. Molecular mimicry at an interspecies or an intracellular level may be involved in altering immune tolerance. On the other hand, studies of epitopes on human autoantigens has provided compelling evidence that most autoantibody responses seen in systemic rheumatic diseases are driven by endogenous antigen.

Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A).

“…Despite extensive investigations into the specificity of human anti-La and anti-Ro6O autoimmune sera (1,2,20), little is known about the extent of immunological tolerance to the La and Ro autoantigens in normal individuals (3). The data presented here demonstrate that anti-La and anti-Ro autoantibody production can be elicited after immunization of normal mice with recombinant mLa in adjuvant.…”

“…Antibodies to the La and Ro ribonucleoproteins (RNPs) are a prominent feature of Sjogren syndrome, yet little is known about how these autoantibodies arise, why they occur together, or indeed the extent of immunological tolerance to these ubiquitous, nuclear/cytoplasmic antigens in normal individuals (1)(2)(3). Considerable evidence suggests that the autoantibody response is antigen-driven and involves T-helper cells.…”

The antichromatin antibodies can be useful as a diagnostic tool and disease activity marker of systemic lupus erythematosus in Koreans

“…Anti-dsDNA antibody has been used as a marker for disease activity, especially in renal disease. But, they are found only in 50% of SLE patients and do not always correlate with disease activity [4]. Therefore, there is a great amount of interest in the identification of other autoantibodies that can be used in the diagnosis and assessment of disease activity in SLE patients.…”

“…The most important diagnostic test for SLE is the detection of the presence of antinuclear antibodies (ANAs), because a negative result virtually rules out the possibility of SLE. However, they have low specificity for the diagnosis of SLE, because they are found in most systemic autoimmune diseases and even in healthy individuals [3,4]. Anti-dsDNA antibody has been used as a marker for disease activity, especially in renal disease.…”

Fator antinúcleo na dermatologia

“…It can be present in proportions that go up to 40% in sclerodermia, poliomyositis, SLE and rheumatoid arthritis. 16,45 Anti-RNA-Polimerase: represented by nucleolar FANA in isolated spots. These are auto-antibodies directed against enzymatic fractions of polipeptides that compose RNA and that are subdivided into three classes -RNA I, II and III.Its positivity is described in SLE, rheumatoid arthritis, sclerodermia, mixed syndrome and overlap syndrome.…”