Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

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Abstract

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or “autoimmunodeficiency” could be the reason for disorders.

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The danger model: a renewed sense of self.

Polly Matzinger (2002)

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.

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Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.

M. M. J. Nielen, Frans Baar, Jan P. Vandenbroucke … (2004)

Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this. Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP. Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.

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Defective B cell tolerance checkpoints in systemic lupus erythematosus

Sergey Yurasov, Hedda Wardemann, Johanna E Hammersen … (2005)

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25–50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5–20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.

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Author and article information

Contributors

Gregory C. Ippolito: Role: Academic Editor

Jagadeesh Bayry: Role: Academic Editor

Journal

Journal ID (nlm-ta): Antibodies (Basel)

Journal ID (iso-abbrev): Antibodies (Basel)

Journal ID (publisher-id): antibodies

Title: Antibodies

Publisher: MDPI

ISSN (Electronic): 2073-4468

Publication date (Electronic): 25 February 2021

Publication date Collection: March 2021

Volume: 10

Issue: 1

Electronic Location Identifier: 9

Affiliations

[1 ]Regional Children’s Clinical Hospital, 620149 Yekaterinburg, Russia; irisha773@ 123456mail.ru

[2 ]Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, 620049 Yekaterinburg, Russia; mchereshneva@ 123456mail.ru (M.V.C.); v.chereshnev@ 123456mail.ru (V.A.C.)

[3 ]Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, 199034 Saint Petersburg, Russia; t.v.fedotkina@ 123456gmail.com (T.V.F.); varvara-ryabkova@ 123456yandex.ru (V.A.R.); elpach@ 123456mail.ru (L.P.C.)

[4 ]Saint Petersburg Research Institute of Phthisiopulmonology, 191036 Saint Petersburg, Russia

Author notes

[* ]Correspondence: irina_pashnina@ 123456list.ru

Author information

Varvara A. Ryabkova https://orcid.org/0000-0001-6973-9901

Leonid P. Churilov https://orcid.org/0000-0001-6359-0026

Article

Publisher ID: antibodies-10-00009

DOI: 10.3390/antib10010009

PMC ID: 8006153

PubMed ID: 33668697

SO-VID: 498309a3-cf4b-400d-a2f9-9924d5a7fde0

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

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Most cited references 204

The danger model: a renewed sense of self.

Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.

Defective B cell tolerance checkpoints in systemic lupus erythematosus

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