The importance of autoantibodies in the etiology, pathogenesis and diagnosis of autoimmune diseases

Antibodies that are directed against self antigens are called autoantibodies. Not all autoantibodies are harmful. Autoantibodies can be useful in the removal of cell debris during inflammation, and autoantibodies to inflammatory cytokines can protect against untoward inflammation. Some autoantibodies may be the actual pathogenetic agents of autoimmune disease, the secondary consequences of tissue damage, or the harmless footprints of an etiologic agent. They can also inform us about basic mechanisms of loss of tolerance and inflammation in patients with autoimmune diseases. Autoantibodies can be present before the onset of some autoimmune diseases, show remarkable specificity and serve as biomarkers providing an opportunity for diagnosis and therapeutic intervention. Titers of some autoantibodies are increased in infections and in a variety of autoimmune diseases and are of little help in the differential diagnosis of disease. By contrast, most of the autoantibodies found in systemic autoimmune diseases are not detected in chronic infections. A negative result for antinuclear antibody (ANA) makes the diagnosis of systemic lupus or other systemic autoimmune disease unlikely, whereas a positive test with a high titer strongly supports the diagnosis. Likewise, in contrast to the high sensitivity and low specificity of rheumatoid factors (RFs) for rheumatoid arthritis, the anti-CCP autoantibody generally has a sensitivity of approximately 50%, but the specificity might be as high as 98%. Approximately 90% of patients with undifferentiated arthritis and raised anti-CCP auto-antibody titers will develop rheumatoid arthritis within few years. The specificity of many auto-antibodies has great diagnostic utility and might also have predictive value, such as with anti-CCP autoantibodies in rheumatoid arthritis. The specificity of autoantibodies in systemic auto-immunity also suggests an intimate relationship with disease pathogenesis. Few autoantibodies can be used alone to diagnose an autoimmune disease, because individuals without overt clinical disease, particularly relatives of patients with autoimmune diseases, might have detectable titers. Furthermore, some autoantibodies, although highly specific, are present only in a minority of patients. For example, autoantibodies to Smith occur in <30% of patients with systemic lupus. For these reasons, detection of autoantibodies is usually used to confirm a clinical diagnosis or help to define a subset of patients within a diagnostic category. In this chapter we discuss, the roles played by autoantibodies in the etiology, pathogenesis and diagnosis of autoimmune diseases with reference to our own experience in this field.