The modern era of rheumatology began in the 1940s with the discovery of rheumatoid factor (RF) (3) and the lupus erythematosus (LE) cells (4), which revealed the presence of immune dysfunction in inflammatory rheumatic diseases. It was originally hoped that laboratory tests for autoantibodies would provide sensitive and specific markers in rheumatic diseases, analogous to cultures in infectious diseases or serum glucose in diabetes.
In the last decades, it has been recognized that most autoantibodies are not specific for a clinical syndrome. They can be detected in patients with markedly different clinical features as well as in some healthy individuals (Table 2).

Table 2 Conditions associated with antinuclear antibodies (ANA)

Several groups of autoantibodies depending on the chemical structures of the corresponding antigens are described (Table 3).

Table 3 Groups of autoantibodies

Autoantibodies	Rheumatoid factor
	Antinuclear antibodies
	Antineutrophil cytoplasmatic antibodies
	Antiphospholipid antibodies
	Antiendothelial antibodies
	Antibodies to blood cells
	Antineuronal antibodies
	Antibodies to stress proteins
	Antibodies to hormones
	Antibodies to microsomes

Although any antibody binding to a self-antigen becomes by definition an autoantibody, the binding may or may not be relevant to autoimmune diseases. Natural antibodies are immunoglobulins that occur in normal individuals and bind to a variety of "self proteins". The function of these autoantibodies is uncertain, but they may serve a beneficial role in helping to clear self molecules from the circulation.
Most of the autoimmune diseases are characterized by the production of autoantibodies which are used as markers of these diseases (1). In autoimmune diseases, autoantibodies may be the actual pathogenic agents of the disease, the secondary consequence of tissue damage, or the footprints of an etiologic agent.
The determination of circulating autoantibodies can be used for the following clinical information:

• Likelihood of an autoimmune disease;
• Specific diagnosis;
• Clinical subtype;
• Disease activity (only possible in a very few cases).

The value of these testings varies depending on the specificity of the assays, the clinical setting, and the disease in question.