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. 1997 Jun;56(6):351–356. doi: 10.1136/ard.56.6.351

Serum immunoglobulins and the risk of rheumatoid arthritis

K Aho 1, M Heliovaara 1, P Knekt 1, A Reunanen 1, A Aromaa 1, A Leino 1, P Kurki 1, R Heikkila 1, T Palosuo 1
PMCID: PMC1752401  PMID: 9227163

Abstract

OBJECTIVE—Rheumatoid arthritis (RA) is associated with several autoantibodies that can precede the clinical disease. The immunoglobulin concentrations in serum samples before illness were studied to learn more about the immunological process before RA.
METHODS—A case-control study was nested within a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. By late 1989, 124 had developed RA, of which 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. The concentrations of IgG, IgA, and IgM were measured from stored serum samples.
RESULTS—Serum IgG before illness was found to be directly proportional to the risk of RF positive RA, and a non-linear association was present between serum IgA and the risk of RF positive RA. These associations were constant between men and women and other subgroups of the study population and not confounded by serum orosomucoid concentration, level of education, smoking, alcohol intake or body mass index. As adjusted for these factors, the odds ratios (95% confidence intervals) of RF positive RA in the lowest, mid, and highest tertiles of IgG distribution were 1.00, 1.55 (0.81, 2.97), and 2.22 (1.16, 4.26), and in the tertiles of IgA 1.00, 2.23 (1.14, 4.36), and 1.78 (0.89, 3.57), respectively. The associations persisted throughout the entire observation period but were most distinct when the period to the onset of clinical RA was ≥ 10 years. IgM carried no predictive significance. None of the serum immunoglobulins predicted the development of RF negative RA.
CONCLUSIONS—Increased IgG levels may reflect some, at present unknown process in the early events leading to the development of RA, typically occurring ≥ 10 years before the onset of clinical disease.



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Selected References

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  1. Aho K., Kurki P. Seropositive versus seronegative rheumatoid arthritis--time for a new definition. J Rheumatol. 1994 Mar;21(3):388–390. [PubMed] [Google Scholar]
  2. Aho K., Palosuo T., Raunio V., Puska P., Aromaa A., Salonen J. T. When does rheumatoid disease start? Arthritis Rheum. 1985 May;28(5):485–489. doi: 10.1002/art.1780280503. [DOI] [PubMed] [Google Scholar]
  3. Aho K., Palusuo T., Kurki P. Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic implications. Semin Arthritis Rheum. 1994 Jun;23(6):379–387. doi: 10.1016/0049-0172(94)90088-4. [DOI] [PubMed] [Google Scholar]
  4. Aho K., Raunio V. EB-virus and rheumatoid arthritis: new insights into their interrelation. Med Biol. 1982 Apr;60(2):49–52. [PubMed] [Google Scholar]
  5. Arden J., Mullinax F., Waller M. Immunoglobulin levels in rheumatoid arthritis: comparison with rheumatoid factor titers, clinical stage and disease duration. Arthritis Rheum. 1967 Jun;10(3):228–234. doi: 10.1002/art.1780100308. [DOI] [PubMed] [Google Scholar]
  6. Bläss S., Specker C., Lakomek H. J., Schneider E. M., Schwochau M. Novel 68 kDa autoantigen detected by rheumatoid arthritis specific antibodies. Ann Rheum Dis. 1995 May;54(5):355–360. doi: 10.1136/ard.54.5.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bond C., Cleland L. G. Rheumatoid arthritis: are pets implicated in its etiology? Semin Arthritis Rheum. 1996 Apr;25(5):308–317. doi: 10.1016/s0049-0172(96)80017-5. [DOI] [PubMed] [Google Scholar]
  8. Cassidy J. T., Nordby G. L., Dodge H. J. Biologic variation of human serum immunoglobulin concentrations: sex-age specific effects. J Chronic Dis. 1974 Dec;27(11-12):507–516. doi: 10.1016/0021-9681(74)90026-5. [DOI] [PubMed] [Google Scholar]
  9. Després N., Boire G., Lopez-Longo F. J., Ménard H. A. The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. J Rheumatol. 1994 Jun;21(6):1027–1033. [PubMed] [Google Scholar]
  10. Farr M., Kitas G. D., Tunn E. J., Bacon P. A. Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis. Br J Rheumatol. 1991 Dec;30(6):413–417. doi: 10.1093/rheumatology/30.6.413. [DOI] [PubMed] [Google Scholar]
  11. Goronzy J. J., Weyand C. M. T and B cell-dependent pathways in rheumatoid arthritis. Curr Opin Rheumatol. 1995 May;7(3):214–221. doi: 10.1097/00002281-199505000-00010. [DOI] [PubMed] [Google Scholar]
  12. Hakala M., Pöllänen R., Nieminen P. The ARA 1987 revised criteria select patients with clinical rheumatoid arthritis from a population based cohort of subjects with chronic rheumatic diseases registered for drug reimbursement. J Rheumatol. 1993 Oct;20(10):1674–1678. [PubMed] [Google Scholar]
  13. Hazes J. M., Dijkmans B. A., Vandenbroucke J. P., de Vries R. R., Cats A. Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption. Ann Rheum Dis. 1990 Dec;49(12):980–982. doi: 10.1136/ard.49.12.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heliövaara M., Aho K., Aromaa A., Knekt P., Reunanen A. Smoking and risk of rheumatoid arthritis. J Rheumatol. 1993 Nov;20(11):1830–1835. [PubMed] [Google Scholar]
  15. Hernández Avila M., Liang M. H., Willett W. C., Stampfer M. J., Colditz G. A., Rosner B., Roberts W. N., Hennekens C. H., Speizer F. E. Reproductive factors, smoking, and the risk for rheumatoid arthritis. Epidemiology. 1990 Jul;1(4):285–291. doi: 10.1097/00001648-199007000-00005. [DOI] [PubMed] [Google Scholar]
  16. Jorgensen C., Anaya J. M., Cognot C., Sany J. Rheumatoid arthritis associated with high levels of immunoglobulin a: clinical and biological characteristics. Clin Exp Rheumatol. 1992 Nov-Dec;10(6):571–575. [PubMed] [Google Scholar]
  17. KING S. H., COBB S. Psychosocial factors in the epidemiology of rheumatoid arthritis. J Chronic Dis. 1958 Jun;7(6):466–475. doi: 10.1016/0021-9681(58)90164-4. [DOI] [PubMed] [Google Scholar]
  18. Kaarela K., Alekberova Z., Lehtinen K., Puolakka K., Koskimies S., Nassonova V., Pospelov L. Seronegative rheumatoid arthritis: a clinical study with HLA typing. J Rheumatol. 1990 Sep;17(9):1125–1129. [PubMed] [Google Scholar]
  19. Kurki P., Aho K., Palosuo T., Heliövaara M. Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the clinical disease. Arthritis Rheum. 1992 Aug;35(8):914–917. doi: 10.1002/art.1780350810. [DOI] [PubMed] [Google Scholar]
  20. Lorber A., Simon T., Leeb J., Peter A., Wilcox S. Chrysotherapy. Suppression of immunoglobulin synthesis. Arthritis Rheum. 1978 Sep-Oct;21(7):785–791. doi: 10.1002/art.1780210708. [DOI] [PubMed] [Google Scholar]
  21. Mageed R. A., Vencovsky J., Maini R. N. Rheumatoid factors and germline genes in rheumatoid arthritis: evidence of an intrinsic B-lymphocyte defect? Br J Rheumatol. 1994 Feb;33(2):105–107. doi: 10.1093/rheumatology/33.2.105. [DOI] [PubMed] [Google Scholar]
  22. Masi A. T. Incidence of rheumatoid arthritis: do the observed age-sex interaction patterns support a role of androgenic-anabolic steroid deficiency in its pathogenesis? Br J Rheumatol. 1994 Aug;33(8):697–699. doi: 10.1093/rheumatology/33.8.697. [DOI] [PubMed] [Google Scholar]
  23. Silman A. J., Newman J., MacGregor A. J. Cigarette smoking increases the risk of rheumatoid arthritis. Results from a nationwide study of disease-discordant twins. Arthritis Rheum. 1996 May;39(5):732–735. doi: 10.1002/art.1780390504. [DOI] [PubMed] [Google Scholar]
  24. Tollerud D. J., Brown L. M., Blattner W. A., Weiss S. T., Maloney E. M., Kurman C. C., Nelson D. L., Hoover R. N. Racial differences in serum immunoglobulin levels: relationship to cigarette smoking, T-cell subsets, and soluble interleukin-2 receptors. J Clin Lab Anal. 1995;9(1):37–41. doi: 10.1002/jcla.1860090107. [DOI] [PubMed] [Google Scholar]
  25. Vessey M. P., Villard-Mackintosh L., Yeates D. Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception. 1987 May;35(5):457–464. doi: 10.1016/0010-7824(87)90082-5. [DOI] [PubMed] [Google Scholar]
  26. Veys E. M., Claessens H. E. Serum levels of IgG, IgM, and IgA in rheumatoid arthritis. Ann Rheum Dis. 1968 Sep;27(5):431–440. doi: 10.1136/ard.27.5.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Voigt L. F., Koepsell T. D., Nelson J. L., Dugowson C. E., Daling J. R. Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology. 1994 Sep;5(5):525–532. [PubMed] [Google Scholar]
  28. Williams A., Scott D. L., Greenwood A., Huskisson E. C. The clinical value of measuring immunoglobulins when assessing penicillamine therapy in rheumatoid arthritis. Clin Rheumatol. 1988 Sep;7(3):347–353. doi: 10.1007/BF02239191. [DOI] [PubMed] [Google Scholar]
  29. Wolfe W. H., Miner J. C., Michalek J. E. Immunological parameters in current and former US Air Force personnel. Vaccine. 1993;11(5):545–547. doi: 10.1016/0264-410x(93)90228-p. [DOI] [PubMed] [Google Scholar]
  30. Youinou P., Serre G. The antiperinuclear factor and antikeratin antibody systems. Int Arch Allergy Immunol. 1995 Aug;107(4):508–518. doi: 10.1159/000237093. [DOI] [PubMed] [Google Scholar]

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