Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1961 Aug 1;114(2):257–278. doi: 10.1084/jem.114.2.257

SPECIFICITY OF THE REACTION BETWEEN RHEUMATOID FACTORS AND GAMMA GLOBULIN

Hugh H Fudenberg 1, Henry G Kunkel 1
PMCID: PMC2137453  PMID: 13702406

Abstract

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human γ-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated γ-globulin or with γ-globulin to form the "22S complex." In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own γ-globulin, compared to that of other individuals of different genetic γ-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own γ-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. DRAY S., YOUNG G. O. Genetic control of two gamma-globulin isoantigenic sites in domestic rabbits. Science. 1960 Mar 11;131(3402):738–739. doi: 10.1126/science.131.3402.738. [DOI] [PubMed] [Google Scholar]
  2. DRAY S., YOUNG G. O. Two antigenically different gamma-globulins in domestic rabbits revealed by isoprecipitins. Science. 1959 Apr 17;129(3355):1023–1025. doi: 10.1126/science.129.3355.1023. [DOI] [PubMed] [Google Scholar]
  3. DUBISKI S., SKALBA D., DUBISKA A., KELUS A. Iso-antigens of rabbit gamma-globulin. Nature. 1959 Dec 5;184(Suppl 23):1811–1812. doi: 10.1038/1841811a0. [DOI] [PubMed] [Google Scholar]
  4. EPSTEIN W., JOHNSON A., RAGAN C. Observations on a precipitin reaction between serum of patients with rheumatoid arthritis and a preparation (Cohn fraction II) of human gamma globulin. Proc Soc Exp Biol Med. 1956 Feb;91(2):235–237. doi: 10.3181/00379727-91-22223. [DOI] [PubMed] [Google Scholar]
  5. FUDENBERG H. H., KUNKEL H. G. Physical properties of the red cell agglutinins in acquired hemolytic anemia. J Exp Med. 1957 Nov 1;106(5):689–702. doi: 10.1084/jem.106.5.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FUDENBERG H., BARRY I., DAMESHEK W. The erythrocyte-coating substance in autoimmune hemolytic disease: its nature and significance. Blood. 1958 Mar;13(3):201–215. [PubMed] [Google Scholar]
  7. FUNDENBERG H. H., ROSENFIELD R. E., WASSERMAN L. R. Unusual specificity of auto-antibody in auto-immune hemolytic diseases. J Mt Sinai Hosp N Y. 1958 Jul-Aug;25(4):324–329. [PubMed] [Google Scholar]
  8. GRUBB R., LAURELL A. B. Hereditary serological human serum groups. Acta Pathol Microbiol Scand. 1956;39(6):390–398. doi: 10.1111/j.1699-0463.1956.tb05067.x. [DOI] [PubMed] [Google Scholar]
  9. HARBOE M. A new haemagglutinating substance in the Gm system, anti-Gm. Nature. 1959 May 23;183(4673):1468–1469. doi: 10.1038/1831468a0. [DOI] [PubMed] [Google Scholar]
  10. HARBOE M., LUNDEVALL J. A new type in the Gm system. Acta Pathol Microbiol Scand. 1959;45(4):357–370. doi: 10.1111/j.1699-0463.1959.tb04721.x. [DOI] [PubMed] [Google Scholar]
  11. HARBOE M. Relation between Gm types and hemagglutinating substances in rheumatoid sera. Acta Pathol Microbiol Scand. 1960;50:89–105. doi: 10.1111/j.1699-0463.1960.tb01175.x. [DOI] [PubMed] [Google Scholar]
  12. HELLER G., JACOBSON A. S., KOLODNY M. H., KAMMERER W. H. The hemagglutination test for rheumatoid arthritis. II. The influence of human plasma fraction II (gamma globulin) on the reaction. J Immunol. 1954 Jan;72(1):66–78. [PubMed] [Google Scholar]
  13. HELLER G., KOLODNY M. H., LEPOW I. H., JACOBSON A. S., RIVERA M. E., MARKS G. H. The hemagglutination test for rheumatoid arthritis. IV. Characterization of the rheumatoid agglutinating factors by analysis of serum fractions prepared by ethanol fractionation. J Immunol. 1955 May;74(5):340–350. [PubMed] [Google Scholar]
  14. HUBINONT P. O., GHYSDAEL P., THYS O. Production of an agglutinating auto-antibody (panagglutinin) active upon tanned erythrocytes in the rabbit. Nature. 1959 Oct 17;184(Suppl 16):1250–1251. doi: 10.1038/1841250a0. [DOI] [PubMed] [Google Scholar]
  15. KUNKEL H. G., FRANKLIN E. C., MULLER-EBERHARD H. J. Studies on the isolation and characterization of the "rheumatoid factor". J Clin Invest. 1959 Feb;38(2):424–434. doi: 10.1172/JCI103817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KUNKEL H. G., FUDENBERG H., OVARY Z. High molecular weight antibodies. Ann N Y Acad Sci. 1960 Jun 30;86:966–973. doi: 10.1111/j.1749-6632.1960.tb42853.x. [DOI] [PubMed] [Google Scholar]
  17. LINNET-JEPSEN P., GALATIUS-JENSEN F., HAUGE M. On the inheritance of the Gm serum group. Acta Genet Stat Med. 1958;8(2):164–196. doi: 10.1159/000151065. [DOI] [PubMed] [Google Scholar]
  18. MACKAY I. R., LARKIN L., BURNET F. M. Failure of autoimmune antibody to react with antigen prepared from the individual's own tissues. Lancet. 1957 Jul 20;273(6986):122–123. doi: 10.1016/s0140-6736(57)91895-0. [DOI] [PubMed] [Google Scholar]
  19. MOULLEC J., KHERUMIAN R., SUTTON E., ESPAGNON P. Contribution a l'étude du facteur de groupe Gma du plasma humain. Rev Hematol. 1956 Nov-Dec;11(5):512–518. [PubMed] [Google Scholar]
  20. MURRAY M. J., THAL A. P. The clinical significance of circulating pancreatic antibodies. Ann Intern Med. 1960 Sep;53:548–555. doi: 10.7326/0003-4819-53-3-548. [DOI] [PubMed] [Google Scholar]
  21. OUDIN J. Allotypy of rabbit serum proteins. I. Immuno-chemical analysis leading to the individualization of seven main allotypes. J Exp Med. 1960 Jul 1;112:107–124. doi: 10.1084/jem.112.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. OUDIN J. Allotypy of rabbit serum proteins. II. Relationships between various allotypes: their common antigenic specificity, their distribution in a sample population; genetic implications. J Exp Med. 1960 Jul 1;112:125–142. doi: 10.1084/jem.112.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. OUDIN J. L'allotypie de certains antigènes protéidiques du sérum. C R Hebd Seances Acad Sci. 1956 May 23;242(21):2606–2608. [PubMed] [Google Scholar]
  24. PLOTZ C. M., SINGER J. M. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Am J Med. 1956 Dec;21(6):888–892. [PubMed] [Google Scholar]
  25. PODLIACHOUK L., JACQUELINE F., EYQUEM A. Le facteur sérique Gm(a) au cours des rhumatismes inflammatoires chroniques. Ann Inst Pasteur (Paris) 1958 May;94(5):590–597. [PubMed] [Google Scholar]
  26. ROSENFIELD R. E., HABER G. V., SCHROEDER R., BALLARD R. Problems in Rh typing as revealed by a single Negro family. Am J Hum Genet. 1960 Jun;12:147–159. [PMC free article] [PubMed] [Google Scholar]
  27. STEINBERG A. G., GILES B. D., STAUFFER R. A Gm-like factor present in Negroes and rare or absent in whites: its relation to Gma and Gmx. Am J Hum Genet. 1960 Mar;12:44–51. [PMC free article] [PubMed] [Google Scholar]
  28. STEINBERG A. G., STAUFFER R. Effect of heat on the serum Gm-a, Gm-b, Gm-x and Gm-like. Nature. 1960 Aug 27;187:791–792. doi: 10.1038/187791a0. [DOI] [PubMed] [Google Scholar]
  29. VAUGHAN J. H. Behavior of the rheumatoid arthritis agglutinating factor with immune precipitates. J Immunol. 1956 Sep;77(3):181–188. [PubMed] [Google Scholar]
  30. VAUGHAN J. H., ELLIS P. J., MARSHALL H. Quantitative considerations of the rheumatoid factor. J Immunol. 1958 Sep;81(3):261–269. [PubMed] [Google Scholar]
  31. VAUGHAN J. H. Serum responses in rheumatoid arthritis. Am J Med. 1959 Apr;26(4):596–613. doi: 10.1016/0002-9343(59)90281-5. [DOI] [PubMed] [Google Scholar]
  32. WALLENIUS G., TRAUTMAN R., KUNKEL H. G., FRANKLIN E. C. Ultracentrifugal studies of major non-lipide electrophoretic components of normal human serum. J Biol Chem. 1957 Mar;225(1):253–267. [PubMed] [Google Scholar]
  33. WALLER M. V., VAUGHAN J. H. Use of anti-Rh sera for demonstrating agglutination activating factor in rheumatoid arthritis. Proc Soc Exp Biol Med. 1956 May;92(1):198–200. doi: 10.3181/00379727-92-22426. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. ZIFF M. The agglutination reaction in rheumatoid arthritis. J Chronic Dis. 1957 Jun;5(6):644–667. doi: 10.1016/0021-9681(57)90074-7. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES