Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Nov;75(11):5697–5701. doi: 10.1073/pnas.75.11.5697

Self-nonself concept for cancer and diseases previously known as “autoimmune” diseases

Philip Levine 1,2
PMCID: PMC393035  PMID: 281717

Abstract

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.

Keywords: illegitimate transferases, plasma exchange

Full text

PDF
5697

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AIRD I., BENTALL H. H., ROBERTS J. A. F. A relationship between cancer of stomach and the ABO blood groups. Br Med J. 1953 Apr 11;1(4814):799–801. doi: 10.1136/bmj.1.4814.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cochrane C. G. Mechanisms involved in the deposition of immune complexes in tissues. J Exp Med. 1971 Sep 1;134(3 Pt 2):75s–89s. [PubMed] [Google Scholar]
  3. Day N. K., Winfield J. B., Gee T., Winchester R., Teshima H., Kunkel H. G. Evidence for immune complexes involving anti-lymphocyte antibodies associated with hypocomplementaemia in chronic lymphocytic leukaemia (CLL). Clin Exp Immunol. 1976 Nov;26(2):189–195. [PMC free article] [PubMed] [Google Scholar]
  4. Green F. A. Phospholipid requirement for Rh antigenic activity. J Biol Chem. 1968 Oct 25;243(20):5519–5521. [PubMed] [Google Scholar]
  5. Hakomori S., Wang S. M., Young W. W., Jr Isoantigenic expression of Forssman glycolipid in human gastric and colonic mucosa: its possible identity with "A-like antigen" in human cancer. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3023–3027. doi: 10.1073/pnas.74.7.3023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kunkel H. G. Immune complexes and disease. General introduction. J Exp Med. 1971 Sep 1;134(3 Pt 2):1s–3s. [PubMed] [Google Scholar]
  7. LEVINE P., BOBBITT O. B., WALLER R. K., KUHMICHEL A. Isoimmunization by a new blood factor in tumor cells. Proc Soc Exp Biol Med. 1951 Jul;77(3):403–405. doi: 10.3181/00379727-77-18794. [DOI] [PubMed] [Google Scholar]
  8. LEVINE P., ROBINSON E., CELANO M., BRIGGS O., FALKINBURG L. Gene interaction resulting in suppression of blood group substance B. Blood. 1955 Nov;10(11):1100–1108. [PubMed] [Google Scholar]
  9. Levine P. Blood group and tissue genetic markers in familial adenocarcinoma: potential specific immunotherapy. Semin Oncol. 1978 Mar;5(1):25–34. [PubMed] [Google Scholar]
  10. Levine P., Tripodi D., Struck J., Jr, Zmijewski C. M., Pollack W. Hemolytic anemia associated with Rh null but not with Bombay blood. A hypothesis based on differing antigenic structures. Vox Sang. 1973 May;24(5):417–424. doi: 10.1111/j.1423-0410.1973.tb03482.x. [DOI] [PubMed] [Google Scholar]
  11. Marcus D. M., Naiki M., Kundu S. K. Abnormalities in the glycosphingolipid content of human Pk and p erythrocytes. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3263–3267. doi: 10.1073/pnas.73.9.3263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Miller G. W., Nussenzweig V. A new complement function: solubilization of antigen-antibody aggregates. Proc Natl Acad Sci U S A. 1975 Feb;72(2):418–422. doi: 10.1073/pnas.72.2.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. OSBORNE R. H., DE GEORGE F. V. The ABO blood groups in parotid and submaxillary gland tumors. Am J Hum Genet. 1962 Jun;14:199–209. [PMC free article] [PubMed] [Google Scholar]
  14. OSBORNE R. H., DEGEORGE F. V. THE ABO BLOOD GROUPS IN NEOPLASTIC DISEASE OF THE OVARY. Am J Hum Genet. 1963 Dec;15:380–388. [PMC free article] [PubMed] [Google Scholar]
  15. Schur P. H. Immune-complex assays: the state of the art. N Engl J Med. 1978 Jan 19;298(3):161–162. doi: 10.1056/NEJM197801192980312. [DOI] [PubMed] [Google Scholar]
  16. Schwarting G. A., Marcus D. M., Metaxas M. Identification of sialosylparagloboside as the erythrocyte receptor for an 'anti-p' antibody. Vox Sang. 1977;32(5):257–261. doi: 10.1111/j.1423-0410.1977.tb00640.x. [DOI] [PubMed] [Google Scholar]
  17. Siddiqui B., Hakomori S. A revised structure for the Forssman glycolipid hapten. J Biol Chem. 1971 Sep 25;246(18):5766–5769. [PubMed] [Google Scholar]
  18. Stellner K., Watanabe K., Hakomori S. Isolation and characterization of glycosphingolipids with blood group H specificity from membranes of human erythrocytes. Biochemistry. 1973 Feb;12(4):656–661. doi: 10.1021/bi00728a014. [DOI] [PubMed] [Google Scholar]
  19. Tachovsky T. G., Lisak R. P., Koprowski H., Theofilopoulos A. N., Dixon F. J. Circulating immune complexes in multiple sclerosis and other neurological diseases. Lancet. 1976 Nov 6;2(7993):997–999. doi: 10.1016/s0140-6736(76)90835-7. [DOI] [PubMed] [Google Scholar]
  20. Teshima H., Wanebo H., Pinsky C., Day N. K. Circulating immune complexes detected by 125I-Clq deviation test in sera of cancer patients. J Clin Invest. 1977 Jun;59(6):1134–1142. doi: 10.1172/JCI108737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Theofilopoulos A. N., Andrews B. S., Urist M. M., Morton D. L., Dixon F. J. The nature of immune complexes in human cancer sera. J Immunol. 1977 Aug;119(2):657–663. [PubMed] [Google Scholar]
  22. WEINER W., BATTEY D. A., CLEGHORN T. E., MARSON F. G. W., MEYNELL M. J. Serological findings in a case of haemolytic anaemia, with some general observations on the pathogenesis of this syndrome. Br Med J. 1953 Jul 18;2(4828):125–128. doi: 10.1136/bmj.2.4828.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wiener A. S. Controversy in human genetics. Blood groups and disease. Am J Hum Genet. 1970 Jul;22(4):476–483. [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES