The reproductive autoimmune failure syndrome

The association between reproductive failure and abnormal autoimmune function has been recognized for decades in association with such established autoimmune diseases as systemic lupus erythematosus. Recent investigations have expanded this association to women who demonstrate similar humoral abnormalities as patients with defined autoimmune diseases but do not express any of the clinical symptoms required for the diagnosis of an autoimmune disease. The observation that abnormal autoimmune function in clinically asymptomatic patients can lead to reproductive failure has led us to define the reproductive autoimmune failure syndrome as a diagnostic entity. The present article summarizes evidence suggesting that the occurrence of reproductive autoimmune failure syndrome may be teleologically related to the woman's need for increased self-tolerance in face of antigenic exposure to the maternal haplotype of the fetus during normal pregnancy. This need for increased self-tolerance is documented by higher normal autoantibody levels in women than in men and may also be responsible for the highly increased incidence of autoimmune diseases in women in comparison with men. Under this concept, abnormal autoimmune function may lead to reproductive failure at different stages of the reproductive process, depending on the quality and possibly quantity of the abnormal autoimmune response.