Self-nonself concept for cancer and diseases previously known as "autoimmune" diseases (illegitimate...

The illegitimate glycosphingolipid antigens of the P blood group system and of the Forssman (Fs) tissue antigen in adenocarcinoma which are foreign to the host suggest the self-nonself concept which applies also to numerous other diseases such as rheumatoid arthritis, lupus, gluomerulonephritis, and idiopathic acute hemolytic anemia. In the presence of the glycosphingolipid antigens such as ABO, P, and Fs, the normal serum of the homozygote recessive precursor contains antibodies for the missing antigen(s). The expected antibody to the Fs antigen was present in about 75% of normal men and women. In cancer sera, the incidence of anti-Fs was decreased to about 35-40%. On testing the normal population anti-Fs was present in 90% of the sera in the youngest group, and this value gradually diminished in the older groups; the incidence of the antibody in the 70-year age group was to about 60%. The rate of loss of anti-Fs with increasing years appears to parallel the gradual loss of anti-A and anti-B isoagglutinin titers. This phenomenon may be associated with the gradual diminution of protein synthesis with aging or the continuous accumulation of soluble immune complexes in the serum, or both. It is suggested that the self-nonself concept is also the basis for the pathogenesis of rhematoid arthritis, lupus erythematosus, idiopathic acute hemolytic anemia, and numerous other conditions classified as "autoimmune" diseases. Some of these diseases are induced by viruses or drugs or both. When a virus or drug attaches itself to the membrane of a tissue cell, the self is converted to nonself which, in rheumatoid arthiritis, alters its self Ig to nonself Ig.