Role of nuclear antigens and antinuclear antibodies in inflammation

Abstract

The sera of patients with lupus erythematosus and other “autosensitivity” diseases, such as rheumatoid arthritis, frequently contain not only the LE cell factor but antinuclear antibodies directed against denatured and native DNA, Sm antigen of the nucleus, protein associated with RNA, and probably many other nuclear antigens. The patients rarely have antibody only to a single nuclear antigen and, furthermore, these antinuclear antibodies are found to be heterogeneous immunoglobulins of the γG, γA, and γM immunoglobulin classes. Data are presented which suggest that at least in rheumatoid arthritis the antibodies may be the result rather than the cause of the disease. Similar antibodies have been elicited by immunization of animals with killed bacteria, human serum, and DNA components conjugated to carrier proteins. Animals with such experimentally induced antibodies do not acquire “human” diseases and it is of further interest that such antinuclear antibodies are found in low concentrations in humans without disease. The above data, taken together with the observations that antinuclear antibodies are generally incapable of injuring intact cells, initially suggest that these antibodies have limited pathogenetic significance. This may not be the case, however, because there is increasing evidence that nuclear antigens and antinuclear antibodies may be one of a series of antigen-antibody combinations capable of eliciting inflammation of the synovium within the joint and along the basement membrane of the renal glomerulus. One animal disease which may bear on this question is Aleutian disease of mink. We have recently had the opportunity to examine 16 pairs of mink sera taken before and after the onset of the disease. Nuclear antigen (DNA) was detected in all these sera both before and after onset of the disease. Only in the diseased animals was antinuclear antibody detectable. It has been suggested by others that the vasculitis and other immunopathologic features of Aleutian disease are due to circulating antigen-antibody complexes even though the disease can be transmitted from mink to mink by filterable material.