Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Jun;92(3):419–424. doi: 10.1111/j.1365-2249.1993.tb03414.x

Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-beta 2m, modified beta 2-microglobulin.

R C Williams Jr 1, M H Nissen 1, C C Malone 1
PMCID: PMC1554767  PMID: 7685671

Abstract

Ten polyclonal IgM rheumatoid factor (RF) preparations, affinity-purified from IgG columns, from patients with rheumatoid arthritis were studied for their ELISA reactivity with native beta 2m in parallel with Lys58-cleaved beta 2m and Des-Lys58-beta 2m, the latter representing cleavage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of beta 2m but reduced reactivity for the cleaved forms of beta 2m. Reactions between cleaved beta 2m and RF, in solution, were demonstrated by inhibition of RF binding to native beta 2m by preincubation with a range of concentrations of Des-Lys58-beta 2m. By contrast, eight of nine murine MoAbs to human beta 2m showed approximately equivalent binding to native beta 2m, Lys58-cleaved beta 2m, and Des-Lys58-beta 2m. Reactions between individual human RF and the altered forms of beta 2m (Lys58-cleaved beta 2m and Des-Lys58-beta 2m) appeared to parallel the previously determined beta 2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-beta 2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved beta 2m or Des-Lys58-beta 2m, preferential reactivity is observed for native unaltered beta 2m.

Full text

PDF
419

Selected References

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

  1. Bjerrum O. W., Nissen M. H., Borregaard N. Neutrophil beta-2 microglobulin: an inflammatory mediator. Scand J Immunol. 1990 Sep;32(3):233–242. doi: 10.1111/j.1365-3083.1990.tb02916.x. [DOI] [PubMed] [Google Scholar]
  2. Getzoff E. D., Geysen H. M., Rodda S. J., Alexander H., Tainer J. A., Lerner R. A. Mechanisms of antibody binding to a protein. Science. 1987 Mar 6;235(4793):1191–1196. doi: 10.1126/science.3823879. [DOI] [PubMed] [Google Scholar]
  3. Geysen H. M., Rodda S. J., Mason T. J., Tribbick G., Schoofs P. G. Strategies for epitope analysis using peptide synthesis. J Immunol Methods. 1987 Sep 24;102(2):259–274. doi: 10.1016/0022-1759(87)90085-8. [DOI] [PubMed] [Google Scholar]
  4. Nardella F. A., Teller D. C., Barber C. V., Mannik M. IgG rheumatoid factors and staphylococcal protein A bind to a common molecular site on IgG. J Exp Med. 1985 Dec 1;162(6):1811–1824. doi: 10.1084/jem.162.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Nardella F. A., Teller D. C., Mannik M. Studies on the antigenic determinants in the self-association of IgG rheumatoid factor. J Exp Med. 1981 Jul 1;154(1):112–125. doi: 10.1084/jem.154.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Nissen M. H., Bjerrum O. J., Plesner T., Wilken M., Rørth M. Modification of beta-2-microglobulin in sera from patients with small cell lung cancer: evidence for involvement of a serine protease. Clin Exp Immunol. 1987 Feb;67(2):425–432. [PMC free article] [PubMed] [Google Scholar]
  7. Nissen M. H., Claësson M. H. Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture. J Immunol. 1987 Aug 15;139(4):1022–1029. [PubMed] [Google Scholar]
  8. Nissen M. H., Plesner T., Rørth M. Modification of beta 2-microglobulin in serum from patients with small cell carcinoma of the lung--correlation with the clinical course. Clin Chim Acta. 1984 Aug 15;141(1):41–50. doi: 10.1016/0009-8981(84)90165-7. [DOI] [PubMed] [Google Scholar]
  9. Nissen M. H., Roepstorff P., Thim L., Dunbar B., Fothergill J. E. Limited proteolysis of beta 2-microglobulin at Lys-58 by complement component C1s. Eur J Biochem. 1990 Apr 30;189(2):423–429. doi: 10.1111/j.1432-1033.1990.tb15505.x. [DOI] [PubMed] [Google Scholar]
  10. Nissen M. H., Thim L., Christensen M. Purification and biochemical characterization of the complete structure of a proteolytically modified beta-2-microglobulin with biological activity. Eur J Biochem. 1987 Feb 16;163(1):21–28. doi: 10.1111/j.1432-1033.1987.tb10731.x. [DOI] [PubMed] [Google Scholar]
  11. Orr H. T., Lancet D., Robb R. J., Lopez de Castro J. A., Strominger J. L. The heavy chain of human histocompatibility antigen HLA-B7 contains an immunoglobulin-like region. Nature. 1979 Nov 15;282(5736):266–270. doi: 10.1038/282266a0. [DOI] [PubMed] [Google Scholar]
  12. Parker K. C., Wiley D. C. Overexpression of native human beta 2-microglobulin in Escherichia coli and its purification. Gene. 1989 Nov 15;83(1):117–124. doi: 10.1016/0378-1119(89)90409-5. [DOI] [PubMed] [Google Scholar]
  13. Peterson P. A., Cunningham B. A., Berggård I., Edelman G. M. 2 -Microglobulin--a free immunoglobulin domain. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1697–1701. doi: 10.1073/pnas.69.7.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Plesner T., Wiik A. Demonstration of electrophoretic heterogeneity of serum beta 2-microglobulin in systemic lupus erythematosus and rheumatoid arthritis: evidence against autoantibodies to beta 2-microglobulin. Scand J Immunol. 1979 Mar;9(3):247–254. doi: 10.1111/j.1365-3083.1979.tb02728.x. [DOI] [PubMed] [Google Scholar]
  15. Saper M. A., Bjorkman P. J., Wiley D. C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol. 1991 May 20;219(2):277–319. doi: 10.1016/0022-2836(91)90567-p. [DOI] [PubMed] [Google Scholar]
  16. Smithies O., Poulik M. D. Initiation of protein synthesis at an unusual position in an immunoglobulin gene? Science. 1972 Jan 14;175(4018):187–189. doi: 10.1126/science.175.4018.187. [DOI] [PubMed] [Google Scholar]
  17. Tam P. E., Messner R. P. Differential inhibition of mitogenic responsiveness by monoclonal antibodies to beta 2-microglobulin. Cell Immunol. 1991 Mar;133(1):219–233. doi: 10.1016/0008-8749(91)90193-f. [DOI] [PubMed] [Google Scholar]
  18. Williams R. C., Jr, Malone C. C., Tsuchiya N. Rheumatoid factors from patients with rheumatoid arthritis react with beta 2-microglobulin. J Immunol. 1992 Aug 1;149(3):1104–1113. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES