Abstract
Rheumatoid factor (RF) production has been demonstrated during infections, including infectious exacerbations of cystic fibrosis (CF). The aim of this study was to evaluate the relationship of RF production to infection, and examine the mechanisms involved. Serial peripheral blood mononuclear cell (PBMC) cultures with measurement of spontaneous production of IgM RF, IgA RF, total IgM and IgA, and measurement of serum levels of immune complexes were carried out during exacerbations of CF. The percentage of B cells expressing CD5 was examined in a second cohort of acutely infected CF patients, and related to IgM RF production. IgM RF production was significantly elevated during acute infection compared with convalescence (P < 0.05), stable CF subjects (P < 0.005) and normal controls (P < 0.05). IgM RF production did not correlate with total IgM production in the majority of patients, but was closely related to circulating immune complex levels in 8/10 subjects. IgA RF production did not increase significantly during infection, and did not correlate with total IgA or IgM RF production, or with circulating immune complex levels. CD5+ B cells were not increased in the CF group, and the percentage of CD5+ B cells did not correlate with IgM RF synthesis. These observations suggest that RF production during infection is specifically induced, possibly by immune complex autoimmunization, and is not simply the result of polyclonal B cell activation. Different patterns of IgM RF and IgA RF synthesis suggest different mechanisms of induction.
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Selected References
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- AHO K., KONTTINEN A., RAJASALMI M., WAGER O. Transient appearance of the rheumatoid factor in connection with prophylactic vaccinations. Acta Pathol Microbiol Scand. 1962;56:478–479. doi: 10.1111/j.1699-0463.1962.tb04201.x. [DOI] [PubMed] [Google Scholar]
- Burastero S. E., Casali P., Wilder R. L., Notkins A. L. Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med. 1988 Dec 1;168(6):1979–1992. doi: 10.1084/jem.168.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Böyum A. Isolation of leucocytes from human blood. Further observations. Methylcellulose, dextran, and ficoll as erythrocyteaggregating agents. Scand J Clin Lab Invest Suppl. 1968;97:31–50. [PubMed] [Google Scholar]
- Carson D. A., Bayer A. S., Eisenberg R. A., Lawrance S., Theofilopoulos A. IgG rheumatoid factor in subacute bacterial endocarditis: relationship to IgM rheumatoid factor and circulating immune complexes. Clin Exp Immunol. 1978 Jan;31(1):100–103. [PMC free article] [PubMed] [Google Scholar]
- Clarkson A. B., Jr, Mellow G. H. Rheumatoid factor-like immunoglobulin M protects previously uninfected rat pups and dams from Trypanosoma lewisi. Science. 1981 Oct 9;214(4517):186–188. doi: 10.1126/science.7025211. [DOI] [PubMed] [Google Scholar]
- Coffey M., Hassan J., Feighery C., Fitzgerald M., Bresnihan B. Rheumatoid factors in cystic fibrosis: associations with disease manifestations and recurrent bacterial infections. Clin Exp Immunol. 1989 Jul;77(1):52–57. [PMC free article] [PubMed] [Google Scholar]
- Cohen P. L., Cheek R. L., Hadler J. A., Yount W. J., Eisenberg R. A. The subclass distribution of human IgG rheumatoid factor. J Immunol. 1987 Sep 1;139(5):1466–1471. [PubMed] [Google Scholar]
- Coulie P., Van Snick J. Rheumatoid factors and secondary immune responses in the mouse. II. Incidence, kinetics and induction mechanisms. Eur J Immunol. 1983 Nov;13(11):895–899. doi: 10.1002/eji.1830131107. [DOI] [PubMed] [Google Scholar]
- Dunne J. V., Carson D. A., Spiegelberg H. L., Alspaugh M. A., Vaughan J. H. IgA rheumatoid factor in the sera and saliva of patients with rheumatoid arthritis and Sjögren's syndrome. Ann Rheum Dis. 1979 Apr;38(2):161–165. doi: 10.1136/ard.38.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FRANKLIN E. C., HOLMAN H. R., MULLER-EBERHARD H. J., KUNKEL H. G. An unusual protein component of high molecular weight in the serum of certain patients with rheumatoid arthritis. J Exp Med. 1957 May 1;105(5):425–438. doi: 10.1084/jem.105.5.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harkiss G. D., Brown D. L., Evans D. B. Longitudinal study of circulating immune complexes in a patient with Staphylococcus albus-induced shunt nephritis. Clin Exp Immunol. 1979 Aug;37(2):228–238. [PMC free article] [PubMed] [Google Scholar]
- Hay F. C., Nineham L. J., Roitt I. M. Routine assay for detection of IgG and IgM antiglobulins in seronegative and seropositive rheumatoid arthritis. Br Med J. 1975 Jul 26;3(5977):203–204. doi: 10.1136/bmj.3.5977.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirsch H. Z., Tarkowski A., Koopman W. J., Mestecky J. Local production of IgA- and IgM-rheumatoid factors in adult periodontal disease. J Clin Immunol. 1989 Jul;9(4):273–278. doi: 10.1007/BF00918658. [DOI] [PubMed] [Google Scholar]
- Izui S., Eisenberg R. A., Dixon F. J. IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides. J Immunol. 1979 May;122(5):2096–2102. [PubMed] [Google Scholar]
- Jasin H. E. The relationship between circulating CD5+ B lymphocytes and in vitro autoantibody synthesis in normal individuals. Cell Immunol. 1991 Aug;136(1):133–141. doi: 10.1016/0008-8749(91)90388-r. [DOI] [PubMed] [Google Scholar]
- Kantor A. B. The development and repertoire of B-1 cells (CD5 B cells). Immunol Today. 1991 Nov;12(11):389–391. doi: 10.1016/0167-5699(91)90136-H. [DOI] [PubMed] [Google Scholar]
- Koopman W. J., Schrohenloher R. E., Czerkinsky C. Differential expression of IgA- and IgM-rheumatoid factors in human disease: evidence for independent regulation of rheumatoid factor isotype production. Adv Exp Med Biol. 1987;216B:1627–1639. [PubMed] [Google Scholar]
- Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
- Nardella F. A., Oppliger I. R., Stone G. C., Sasso E. H., Mannik M., Sjöquist J., Schröder A. K., Christensen P., Johansson P. J., Björck L. Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to the Fc binding proteins of microorganisms. Scand J Rheumatol Suppl. 1988;75:190–198. doi: 10.3109/03009748809096761. [DOI] [PubMed] [Google Scholar]
- Nemazee D. A. Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice. J Exp Med. 1985 Jan 1;161(1):242–256. doi: 10.1084/jem.161.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nemazee D. A. Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice. J Exp Med. 1985 Jan 1;161(1):242–256. doi: 10.1084/jem.161.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Farrelly C., Price R., McGillivray A. J., Fernandes L. IgA rheumatoid factor and IgG dietary protein antibodies are associated in rheumatoid arthritis. Immunol Invest. 1989 Jul;18(6):753–764. doi: 10.3109/08820138909030596. [DOI] [PubMed] [Google Scholar]
- Oppliger I. R., Nardella F. A., Stone G. C., Mannik M. Human rheumatoid factors bear the internal image of the Fc binding region of staphylococcal protein A. J Exp Med. 1987 Sep 1;166(3):702–710. doi: 10.1084/jem.166.3.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Snick J., Coulie P. Rheumatoid factors and secondary immune responses in the mouse. I. Frequent occurrence of hybridomas secreting IgM anti-IgG1 autoantibodies after immunization with protein antigens. Eur J Immunol. 1983 Nov;13(11):890–894. doi: 10.1002/eji.1830131106. [DOI] [PubMed] [Google Scholar]
- WILLIAMS R. C., Jr, KUNKEL H. G. Antibodies to rabbit gamma-globulin after immunizing with various preparations of autologous gamma-globulin. Proc Soc Exp Biol Med. 1963 Mar;112:554–561. doi: 10.3181/00379727-112-28104. [DOI] [PubMed] [Google Scholar]
- WILLIAMS R. C., Jr, KUNKEL H. G. Rheumatoid factor, complement, and conglutinin aberrations in patients with subacute bacterial endocarditis. J Clin Invest. 1962 Mar;41:666–675. doi: 10.1172/JCI104523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welch M. J., Fong S., Vaughan J., Carson D. Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid. Clin Exp Immunol. 1983 Feb;51(2):299–304. [PMC free article] [PubMed] [Google Scholar]
- Williams R. C. Rheumatoid factors in subacute bacterial endocarditis and other infectious diseases. Scand J Rheumatol Suppl. 1988;75:300–308. doi: 10.3109/03009748809096782. [DOI] [PubMed] [Google Scholar]
