Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1989 Jul;77(1):52–57.

Rheumatoid factors in cystic fibrosis: associations with disease manifestations and recurrent bacterial infections.

M Coffey 1, J Hassan 1, C Feighery 1, M Fitzgerald 1, B Bresnihan 1
PMCID: PMC1541909  PMID: 2766578

Abstract

Serum IgM and IgA rheumatoid factor (RF) levels were measured by ELISA in 71 adolescent and adult patients with cystic fibrosis (CF) and 69 control subjects. IgM RF values from 15 (21%) CF patients greater than 2 s.d. of control subjects (P less than 0.001). Elevated IgM RF values were significantly associated with worse spirometric measurements of pulmonary function (P less than 0.01) and with more frequent exacerbations of respiratory tract infection (P less than 0.001). A characteristic episodic arthropathy occurred in 27% of IgM RF positive patients, compared with 4% of IgM RF negative patients (P = 0.015). IgA RF values from 26 (37%) CF patients were elevated (P less than 0.001). Pulmonary function was significantly worse in patients with elevated IgA RF values (P less than 0.001). However, IgA RF was not associated with exacerbations of respiratory tract infection or episodic arthropathy. Both IgM and IgA RF values correlated significantly with their corresponding Ig levels, suggesting that RF synthesis was the result of polyclonal B cell activation. It is concluded that serum IgM RF values in CF are associated with worse lung disease and recurring bacterial antigenic stimulation. IgM RF may contribute to the development of arthropathy in some patients. Induction of IgA RF synthesis and its pathogenic potential may differ from IgM RF.

Full text

PDF
52

Selected References

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

  1. BAUM J., STASTNY P., ZIFF M. EFFECTS OF THE RHEUMATOID FACTOR AND ANTIGEN-ANTIBODY COMPLEXES ON THE VESSELS OF THE RAT MESENTERY. J Immunol. 1964 Dec;93:985–992. [PubMed] [Google Scholar]
  2. BUNIM J. J., BUCHANAN W. W., WERTLAKE P. T., SOKOLOFF L., BLOCH K. J., BECK J. S., ALEPA F. P. CLINICAL, PATHOLOGIC, AND SEROLOGIC STUDIES IN SJOEGREN'S SYNDROME; COMBINED CLINICAL STAFF CONFERENCE AT THE NATIONAL INSTITUTES OF HEALTH. Ann Intern Med. 1964 Sep;61:509–530. doi: 10.7326/0003-4819-61-3-509. [DOI] [PubMed] [Google Scholar]
  3. Boackle R. J., Pruitt K. M., Mestecky J. The interactions of human complement with interfacially aggregated preparations of human secretory IgA. Immunochemistry. 1974 Sep;11(9):543–548. doi: 10.1016/0019-2791(74)90245-6. [DOI] [PubMed] [Google Scholar]
  4. Bokisch V. A., Bernstein D., Krause R. M. Occurrence of 19S and 7S anti-IgGs during hyperimmunization of rabbits with streptococci. J Exp Med. 1972 Oct 1;136(4):799–815. doi: 10.1084/jem.136.4.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bourke S., Rooney M., Fitzgerald M., Bresnihan B. Episodic arthropathy in adult cystic fibrosis. Q J Med. 1987 Aug;64(244):651–659. [PubMed] [Google Scholar]
  6. Braude S., Kennedy H., Hodson M., Batten J. Hypertrophic osteoarthropathy in cystic fibrosis. Br Med J (Clin Res Ed) 1984 Mar 17;288(6420):822–823. doi: 10.1136/bmj.288.6420.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Capra J. D., Winchester R. J., Kunkel H. G. Hypergammaglobulinemic purpura. Studies on the unusual anti- -globulins characteristic of the sera of these patients. Medicine (Baltimore) 1971 Mar;50(2):125–138. [PubMed] [Google Scholar]
  8. 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]
  9. Carson D. A., Lawrance S., Catalano M. A., Vaughan J. H., Abraham G. Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG. J Immunol. 1977 Jul;119(1):295–300. [PubMed] [Google Scholar]
  10. 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]
  11. DeHoratius R. J., Williams R. C., Jr Rheumatoid factor accentuation of pulmonary lesions associated with experimental diffuse proliferative lung disease. Arthritis Rheum. 1972 May-Jun;15(3):293–301. doi: 10.1002/art.1780150311. [DOI] [PubMed] [Google Scholar]
  12. Dixey J., Redington A. N., Butler R. C., Smith M. J., Batchelor J. R., Woodrow D. F., Hodson M. E., Batten J. C., Brewerton D. A. The arthropathy of cystic fibrosis. Ann Rheum Dis. 1988 Mar;47(3):218–223. doi: 10.1136/ard.47.3.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dresser D. W. Most IgM-producing cells in the mouse secrete auto-antibodies (rheumatoid factor). Nature. 1978 Aug 3;274(5670):480–483. doi: 10.1038/274480a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Elkon K. B., Delacroix D. L., Gharavi A. E., Vaerman J. P., Hughes G. R. Immunoglobulin A and polymeric IgA rheumatoid factors in systemic sicca syndrome: partial characterization. J Immunol. 1982 Aug;129(2):576–581. [PubMed] [Google Scholar]
  16. Faith A., Pontesilli O., Unger A., Panayi G. S., Johns P. ELISA assays for IgM and IgG rheumatoid factors. J Immunol Methods. 1982 Dec 17;55(2):169–177. doi: 10.1016/0022-1759(82)90029-1. [DOI] [PubMed] [Google Scholar]
  17. Gamble C. N., Reardan J. B. Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits. N Engl J Med. 1975 Feb 27;292(9):449–454. doi: 10.1056/NEJM197502272920903. [DOI] [PubMed] [Google Scholar]
  18. Grey H. M., Kohler P. F., Terry W. D., Franklin E. C. Human monoclonal gamma G-cryoglobulins with anti-gamma-globulin activity. J Clin Invest. 1968 Aug;47(8):1875–1884. doi: 10.1172/JCI105878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Grigor R., Edmonds J., Lewkonia R., Bresnihan B., Hughes G. R. Systemic lupus erythematosus. A prospective analysis. Ann Rheum Dis. 1978 Apr;37(2):121–128. doi: 10.1136/ard.37.2.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gutman R. A., Striker G. E., Gilliland B. C., Cutler R. E. The immune complex glomerulonephritis of bacterial endocarditis. Medicine (Baltimore) 1972 Jan;51(1):1–25. doi: 10.1097/00005792-197201000-00001. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Iveson J. M., McDougall A. C., Leathem A. J., Harris H. J. Lepromatous leprosy presenting with polyarthritis, myositis, and immune-complex glomerulonephritis. Br Med J. 1975 Sep 13;3(5984):619–621. doi: 10.1136/bmj.3.5984.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Mathieu J. P., Stack B. H., Dick W. C., Buchanan W. W. Pulmonary infection and rheumatoid arthritis. Br J Dis Chest. 1978 Jan;72(1):57–61. doi: 10.1016/0007-0971(78)90007-4. [DOI] [PubMed] [Google Scholar]
  26. Munthe E., Natvig J. B. Characterization of IgG complexes in eluates from rheumatoid tissue. Clin Exp Immunol. 1971 Feb;8(2):249–262. [PMC free article] [PubMed] [Google Scholar]
  27. Newman A. J., Ansell B. M. Episodic arthritis in children with cystic fibrosis. J Pediatr. 1979 Apr;94(4):594–596. doi: 10.1016/s0022-3476(79)80018-9. [DOI] [PubMed] [Google Scholar]
  28. Penketh A. R., Wise A., Mearns M. B., Hodson M. E., Batten J. C. Cystic fibrosis in adolescents and adults. Thorax. 1987 Jul;42(7):526–532. doi: 10.1136/thx.42.7.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pfaffenbach G., Lamm M. E., Gigli I. Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes. J Exp Med. 1982 Jan 1;155(1):231–247. doi: 10.1084/jem.155.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Phillips B. M., David T. J. Pathogenesis and management of arthropathy in cystic fibrosis. J R Soc Med. 1986;79 (Suppl 12):44–50. [PMC free article] [PubMed] [Google Scholar]
  31. Rush P. J., Shore A., Coblentz C., Wilmot D., Corey M., Levison H. The musculoskeletal manifestations of cystic fibrosis. Semin Arthritis Rheum. 1986 Feb;15(3):213–225. doi: 10.1016/0049-0172(86)90018-1. [DOI] [PubMed] [Google Scholar]
  32. Sabharwal U. K., Vaughan J. H., Fong S., Bennett P. H., Carson D. A., Curd J. G. Activation of the classical pathway of complement by rheumatoid factors. Assessment by radioimmunoassay for C4. Arthritis Rheum. 1982 Feb;25(2):161–167. doi: 10.1002/art.1780250208. [DOI] [PubMed] [Google Scholar]
  33. Sagransky D. M., Greenwald R. A., Gorvoy J. D. Seropositive rheumatoid arthritis in a patient with cystic fibrosis. Am J Dis Child. 1980 Mar;134(3):319–320. doi: 10.1001/archpedi.1980.02130150073020. [DOI] [PubMed] [Google Scholar]
  34. Schidlow D. V., Goldsmith D. P., Palmer J., Huang N. N. Arthritis in cystic fibrosis. Arch Dis Child. 1984 Apr;59(4):377–379. doi: 10.1136/adc.59.4.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schrohenloher R. E., Koopman W. J., Alarcón G. S. Molecular forms of IgA rheumatoid factor in serum and synovial fluid of patients with rheumatoid arthritis. Arthritis Rheum. 1986 Oct;29(10):1194–1202. doi: 10.1002/art.1780291003. [DOI] [PubMed] [Google Scholar]
  36. Soter N. A., Mihm M. C., Jr, Colten H. R. Cutaneous necrotizing venulitis in patients with cystic fibrosis. J Pediatr. 1979 Aug;95(2):197–201. doi: 10.1016/s0022-3476(79)80650-2. [DOI] [PubMed] [Google Scholar]
  37. Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med. 1978 Apr 20;298(16):869–871. doi: 10.1056/NEJM197804202981602. [DOI] [PubMed] [Google Scholar]
  38. Summers G. D., Webley M. Episodic arthritis in cystic fibrosis: a case report. Br J Rheumatol. 1986 Nov;25(4):393–395. doi: 10.1093/rheumatology/25.4.393. [DOI] [PubMed] [Google Scholar]
  39. Theofilopoulos A. N., Burtonboy G., LoSpalluto J. J., Ziff M. IgM rheumatoid factor and low molecular weight IgM. An association with vasculitis. Arthritis Rheum. 1974 May-Jun;17(3):272–284. doi: 10.1002/art.1780170312. [DOI] [PubMed] [Google Scholar]
  40. Torrigiani G., Roitt I. M. Antiglobulin factors in sera from patients with rheumatoid arthritis and normal subjects. Quantitative estimation in different immunoglobulin classes. Ann Rheum Dis. 1967 Jul;26(4):334–340. doi: 10.1136/ard.26.4.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Van Snick J. L. The production of anti-IgG2a autoantibody in the 129/Sv mouse: onset in the lymph nodes draining the intestinal tract and prevention by neonatal thymectomy. J Immunol. 1981 Mar;126(3):815–818. [PubMed] [Google Scholar]
  42. Van Snick J. L., Van Roost E., Markowetz B., Cambiaso C. L., Masson P. L. Enhancement by IgM rheumatoid factor of in vitro ingestion by macrophages and in vivo clearance of aggregated IgG or antigen-antibody complexes. Eur J Immunol. 1978 Apr;8(4):279–285. doi: 10.1002/eji.1830080412. [DOI] [PubMed] [Google Scholar]
  43. Vaze D. Episodic arthritis in cystic fibrosis. J Pediatr. 1980 Feb;96(2):346–346. doi: 10.1016/s0022-3476(80)80850-x. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Walker L. C., Ahlin T. D., Tung K. S., Williams R. C., Jr Circulating immune complexes in disseminated gonorrheal infection. Ann Intern Med. 1978 Jul;89(1):28–33. doi: 10.7326/0003-4819-89-1-28. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Wheeler W. B., Williams M., Matthews W. J., Jr, Colten H. R. Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study. J Pediatr. 1984 May;104(5):695–699. doi: 10.1016/s0022-3476(84)80946-4. [DOI] [PubMed] [Google Scholar]
  48. Winchester R. J., Agnello V., Kunkel H. G. Gamma globulin complexes in synovial fluids of patients with rheumatoid arthritis. Partial characterization and relationship to lowered complement levels. Clin Exp Immunol. 1970 May;6(5):689–706. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES