Neonatal Autoimmune Diseases Caused by Maternal Pathogenic Autoantibodies

Abstract

B cells exhibit the capacity to synthesize antibodies that are specific for both foreign and self-antigens. Active immunization with T-cell-dependent or -independent foreign antigens leads to production of antibodies with exquisite specificity for epitopes born by a large complement of foreign antigens. However, B cells can produce antibodies that display activity to self-antigens. Self-reactive antibodies are classified in three major categories:

• a. Natural, polyspecific autoantibodies. This subset constitutes a substantial fraction of the self-reactive repertoire. “Natural” serum antibodies are found in most species and are comprised of various Ig subclasses (IgM, IgG, IgA). They bind with moderate or low affinity to structurally dissimilar epitopes born by foreign and self-molecules (720). In humans and mice, they are produced by CD5+ B cells (721), a subset that is enlarged in some animal strains prone to autoimmune disease (722). Polyspecific autoantibodies can be found in increased concentrations in the blood of patients with autoimmune diseases, without induction of injury to normal tissue (723).

• b. Autoantibodies with exquisite specificity for autoantigens. These autoantibodies exhibit high binding affinity to self-antigens and can be found at low levels in healthy humans and animals. Their concentration can be increased in some autoimmune diseases and may be used as a diagnostic criterion (e.g., antitopoisomerase I in scleroderma; anticentromere in calcinosis, Reynaud’s phenomenon, esophageal motility disorders, s clerodactyly, and telangiectasia [CREST] syndrome; anti-transfer RNA (tRNA) synthetase or anti-Jo1 in polymyositis; and rheumatoid factor in rheumatoid arthritis). In certain conditions, autoantibodies can be pathogenic, as is the case of antithyroglobulin autoantibodies. Antithyroglobulin antibodies with similar epitope specificities are found in 50–70% of patients with autoimmune thyroiditis and 10–20% of normal subjects (724,725).

• c. Pathogenic autoantibodies. These autoantibodies appear to facilitate the onset of autoimmune disease that causes injury to tissue bearing specific target autoantigens. Although they lack particular immunochemical properties, they exhibit distinct physiopathological properties. Production of pathogenic autoantibodies results either from breakdown of central or peripheral tolerance for self-antigens or from immunization of mother with father antigens resulting from selfantigens displaying allelic polymorphism.