Rom J Morphol Embryol 2016, 57(2 Suppl):633–638 ISSN (print) 1220–0522 ISSN (online) 2066–8279 REVIEW The role of autoantibodies in health and disease ISABELA SILOŞI 1) , CRISTIAN ADRIAN SILOŞI 1) , MIHAIL VIRGIL BOLDEANU 1) , MANOLE COJOCARU 2) , VIOREL BICIUŞCĂ 1) , CARMEN SILVIA AVRĂMESCU 1) , INIMIOARA MIHAELA COJOCARU 3) , MARIA BOGDAN 4) , ROXANA MIHAELA FOLCUŢI 1) 1) Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania 2) Department of Physiology, Faculty of Medicine, “Titu Maiorescu” University, Bucharest, Romania 3) Department of Neurology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 4) Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania Abstract Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases. The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease. Keywords: autoantibodies, physiological functions, autoimmune diseases, malignant diseases.  Introduction The synthesis of antibodies is a vital way in which adaptive immune system works for the recognition and response to external threats. Some antibodies that are present in sera of healthy individuals, outside immuni- zation with any antigen, and react with a variety of endo- genous and exogenous antigens, are considered natural autoantibodies (NAA) [1]. Boyden first mentioned the term “natural autoantibodies”, in 1963, after being identified autoreactive responses in sera of healthy persons [2]. The majority of NAA are particularly IgM isotype encoded by unmutated variable, diversity and joining [V(D)J] gene segments and display a moderate affinity for self-antigens. It considered that NAA are present from birth, represent a substantial proportion of the normal antibodies, and contribute to the stimulation of primitive innate system [3–5]. Many works demonstrated that auto- reactive B-cells, a substantial part of the B-cell repertoire, secretes NAA characterized by their broad reactivity directed against very well conserved public epitopes [6]. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies can cause tissue damage or malfunctions and induce auto- immune diseases, through binding to self-proteins [7–9]. IgM-NAA are produced by B-1 cells and intervene in defense against systemic bacterial and viral infections. B-1 cells are very efficient antigen presentation cells and may have an important role in the synthesis of pathogenic autoantibodies reported in patients with autoimmune diseases, as rheumatoid arthritis, Sjögren’s syndrome, primary antiphospholipid syndrome and systemic lupus [10, 11]. The trigger antigens for autoantibodies may be found in all cell types (e.g., chromatin) or be highly specific for a certain cell type in one organ of the body (e.g., thyroglobulin in cells of the thyroid gland). They can be represented by serum proteins, nucleic acids, carbo- hydrates, lipids, erythrocytes, cellular components, insulin [9]. The aim of our paper is to review the functional properties of NAA as well as the association of auto- antibodies with some diseases pathogenesis, in order to enhance understanding of both natural autoimmunity and autoimmune disease mechanisms.  Natural autoantibodies in health (physiological functions) The generation of NAA against self-antigens is a common phenomenon in humans; their low-affinity, potentially autoreactive cells persist to self-antigens is required for survival of T- and probably B-lymphocytes in the peripheral immune system. Because natural auto- antibodies also recognize a wide variety of self-antigens, they have an important role in the development of the B-cell repertoire [6]. Principal characteristics of NAA are indicated in Table 1 [12]. R J M E Romanian Journal of Morphology & Embryology http://www.rjme.ro/