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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Sep;69(3):557–565.

High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population.

M N Manoussakis 1, A G Tzioufas 1, M P Silis 1, P J Pange 1, J Goudevenos 1, H M Moutsopoulos 1
PMCID: PMC1542366  PMID: 3499270

Abstract

Serum samples from 64 apparently healthy individuals (32 men and 32 women, mean age 81.0 years) were examined for the prevalence of several autoantibodies, including rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to extracted cellular antigens Ro (SSA), La (SSB), Sm, U1nRNP and Scl-70. IgG and IgM isotype-specific ELISA methods were applied for the detection of antibodies to ssDNA (anti-ssDNA), to dsDNA (anti-dsDNA) and to cardiolipin (anti-CL). The sera of this elderly population were found to contain a plethora of autoantibodies; RF was detected in 14.1%, ANA in 31.3% and anti-Ro (SSA) in 1.6% of the individuals. Precipitating antibodies to La (SSB), Sm, U1nRNP and Scl-70 were absent, while 15.6% of the sera displayed precipitating antibodies to a common undefined human spleen antigen. ELISA methods revealed anti-ssDNA in 17.2% of the individuals, anti-dsDNA in 14.1% and anti-CL in an extremely high incidence (51.6%). Notably, the above autoantibodies were exclusively of IgG isotype. Tests of 261 sera from healthy non-elderly individuals disclosed only anti-CL (IgG and IgM isotypes) in 2.3% of them. The levels of IgA and IgG immunoglobulins were increased in 23.4% and 29.7% of the elderly subjects, respectively. IgM was elevated in 3.1%, but it was also found decreased in 9.4%. This study documents the high incidence of autoantibodies in the healthy elderly, including for the first time, anti-CL antibodies. Furthermore, the relative impairment in IgM autoantibody production observed, possibly indicates the involution of the senescent immune system.

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Selected References

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  1. Alspaugh M. A., Buchanan W. W., Whaley K. Precipitating antibodies to cellular antigens in Sjögren's syndrome, rheumatoid arthritis, and other organ and nonorgan-specific autoimmune diseases. Ann Rheum Dis. 1978 Jun;37(3):244–246. doi: 10.1136/ard.37.3.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buckley C. E., 3rd, Buckley E. G., Dorsey F. C. Longitudinal changes in serum immunoglobulin levels in older humans. Fed Proc. 1974 Sep;33(9):2036–2039. [PubMed] [Google Scholar]
  3. Cammarata R. J., Rodnan G. P., Fennell R. H. Serum anti-gamma-globulin and antinuclear factors in the aged. JAMA. 1967 Feb 13;199(7):455–458. [PubMed] [Google Scholar]
  4. Ceuppens J. L., Goodwin J. S. Regulation of immunoglobulin production in pokeweed mitogen-stimulated cultures of lymphocytes from young and old adults. J Immunol. 1982 Jun;128(6):2429–2434. [PubMed] [Google Scholar]
  5. Delespesse G., Duchateau J., Bastenie P. A., Lauvaux J. P., Collet H., Govaerts A. Cell-mediated immunity in diabetes mellitus. Clin Exp Immunol. 1974 Dec;18(4):461–467. [PMC free article] [PubMed] [Google Scholar]
  6. Delespesse G., Gausset P., Sarfati M., Dubi-Rucquoy M., Debisschop M. J., van Haelst L. Circulating immune complexes in old people and in diabetics: correlation with autoantibodies. Clin Exp Immunol. 1980 Apr;40(1):96–102. [PMC free article] [PubMed] [Google Scholar]
  7. Delfraissy J. F., Galanaud P., Dormont J., Wallon C. Age-related impairment of the in vitro antibody response in the human. Clin Exp Immunol. 1980 Jan;39(1):208–214. [PMC free article] [PubMed] [Google Scholar]
  8. Diaz-Jauanen E., Strickland R. G., Williams R. C. Studies of human lymphocytes in the newborn and the aged. Am J Med. 1975 May;58(5):620–628. doi: 10.1016/0002-9343(75)90497-0. [DOI] [PubMed] [Google Scholar]
  9. Eaton R. B., Schnneider G., Schur P. H. Enzyme immunoassay for antibodies to native DNA. Specificity and quality of antibodies. Arthritis Rheum. 1983 Jan;26(1):52–62. doi: 10.1002/art.1780260109. [DOI] [PubMed] [Google Scholar]
  10. Ennist D. L., Jones K. H., St Pierre R. L., Whisler R. L. Functional analysis of the immunosenescence of the human B cell system: dissociation of normal activation and proliferation from impaired terminal differentiation into IgM immunoglobulin-secreting cells. J Immunol. 1986 Jan;136(1):99–105. [PubMed] [Google Scholar]
  11. Friedman D., Globerson A. Immune reactivity during aging. II. Analysis of the cellular mechanisms involved in the deficient antibody response in old mice. Mech Ageing Dev. 1978 Apr;7(4):299–307. doi: 10.1016/0047-6374(78)90073-8. [DOI] [PubMed] [Google Scholar]
  12. Gharavi A. E., Harris E. N., Asherson R. A., Hughes G. R. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis. 1987 Jan;46(1):1–6. doi: 10.1136/ard.46.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodwin J. S., Searles R. P., Tung K. S. Immunological responses of healthy elderly population. Clin Exp Immunol. 1982 May;48(2):403–410. [PMC free article] [PubMed] [Google Scholar]
  14. Gordon J., Rosenthal M. Failure to detect age-related increase of non-pathological autoantibodies. Lancet. 1984 Jan 28;1(8370):231–231. doi: 10.1016/s0140-6736(84)92157-3. [DOI] [PubMed] [Google Scholar]
  15. HACKETT E., BEECH M., FORBES I. J. Thyrogloubulin antibodies in patients without clinical disease of the thyroid gland. Lancet. 1960 Aug 20;2(7147):402–404. doi: 10.1016/s0140-6736(60)92842-7. [DOI] [PubMed] [Google Scholar]
  16. HEIMER R., LEVIN F. M., RUDD E. GLOBULINS RESEMBLING RHEUMATOID FACTOR IN SERUM OF THE AGED. Am J Med. 1963 Aug;35:175–181. doi: 10.1016/0002-9343(63)90208-0. [DOI] [PubMed] [Google Scholar]
  17. Hallgren H. M., Buckley C. E., 3rd, Gilbertsen V. A., Yunis E. J. Lymphocyte phytohemagglutinin responsiveness, immunoglobulins and autoantibodies in aging humans. J Immunol. 1973 Oct;111(4):1101–1107. [PubMed] [Google Scholar]
  18. Harris E. N., Gharavi A. E., Hughes G. R. Anti-phospholipid antibodies. Clin Rheum Dis. 1985 Dec;11(3):591–609. [PubMed] [Google Scholar]
  19. Harris E. N., Gharavi A. E., Loizou S., Derue G., Chan J. K., Patel B. M., Mackworth-Young C. G., Bunn C. C., Hughes G. R. Crossreactivity of antiphospholipid antibodies. J Clin Lab Immunol. 1985 Jan;16(1):1–6. [PubMed] [Google Scholar]
  20. Hijmans W., Radl J., Bottazzo G. F., Doniach D. Autoantibodies in highly aged humans. Mech Ageing Dev. 1984 Jul;26(1):83–89. doi: 10.1016/0047-6374(84)90167-2. [DOI] [PubMed] [Google Scholar]
  21. Kasjanov A., Cebecauer L., Baláz V. Antibodies against ss-DNA in persons of various age. Mech Ageing Dev. 1984 Dec;28(2-3):289–295. doi: 10.1016/0047-6374(84)90029-0. [DOI] [PubMed] [Google Scholar]
  22. Kishimoto S., Tomino S., Mitsuya H., Fujiwara H., Tsuda H. Age-related decline in the in vitro and in vivo syntheses of anti-tetanus toxoid antibody in humans. J Immunol. 1980 Nov;125(5):2347–2352. [PubMed] [Google Scholar]
  23. Kurata N., Tan E. M. Identification of antibodies to nuclear acidic antigens by counterimmunoelectrophoresis. Arthritis Rheum. 1976 May-Jun;19(3):574–580. doi: 10.1002/art.1780190309. [DOI] [PubMed] [Google Scholar]
  24. Lafer E. M., Rauch J., Andrzejewski C., Jr, Mudd D., Furie B., Furie B., Schwartz R. S., Stollar B. D. Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med. 1981 Apr 1;153(4):897–909. doi: 10.1084/jem.153.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mackay I. R. Ageing and immunological function in man. Gerontologia. 1972;18(5-6):285–304. doi: 10.1159/000211941. [DOI] [PubMed] [Google Scholar]
  26. Mascart-Lemone F., Delespesse G., Servais G., Kunstler M. Characterization of immunoregulatory T lymphocytes during ageing by monoclonal antibodies. Clin Exp Immunol. 1982 Apr;48(1):148–154. [PMC free article] [PubMed] [Google Scholar]
  27. Moulias R., Proust J., Wang A., Congy F., Marescot M. R., Deville Chabrolle A., Paris Hamelin A., Lesourd B. Age-related increase in autoantibodies. Lancet. 1984 May 19;1(8386):1128–1129. doi: 10.1016/s0140-6736(84)92547-9. [DOI] [PubMed] [Google Scholar]
  28. Pandey J. P., Fudenberg H. H., Ainsworth S. K., Loadholt C. B. Autoantibodies in healthy subjects of different age groups. Mech Ageing Dev. 1979 Jul;10(6):399–404. doi: 10.1016/0047-6374(79)90021-6. [DOI] [PubMed] [Google Scholar]
  29. Price G. B., Makinodan T. Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies. J Immunol. 1972 Feb;108(2):403–412. [PubMed] [Google Scholar]
  30. Radl J., Sepers J. M., Skvaril F., Morell A., Hijmans W. Immunoglobulin patterns in humans over 95 years of age. Clin Exp Immunol. 1975 Oct;22(1):84–90. [PMC free article] [PubMed] [Google Scholar]
  31. Roberts-Thomson I. C., Whittingham S., Youngchaiyud U., Mackay I. R. Ageing, immune response, and mortality. Lancet. 1974 Aug 17;2(7877):368–370. doi: 10.1016/s0140-6736(74)91755-3. [DOI] [PubMed] [Google Scholar]
  32. Schuller E., Allinquant B., Reboul J., Fournier C., Dardenne M., Bach J. F. Immunological studies in human ageing. II. Associated increase in anti-RNA and anti-DNA antibodies. J Clin Lab Immunol. 1981 Sep;6(2):107–110. [PubMed] [Google Scholar]
  33. Seligmann M., Cannat A., Hamard M. Studies on antinuclear antibodies. Ann N Y Acad Sci. 1965 Jun 30;124(2):816–832. doi: 10.1111/j.1749-6632.1965.tb19004.x. [DOI] [PubMed] [Google Scholar]
  34. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  35. Silvestris F., Anderson W., Goodwin J. S., Williams R. C., Jr Discrepancy in the expression of autoantibodies in healthy aged individuals. Clin Immunol Immunopathol. 1985 May;35(2):234–244. doi: 10.1016/0090-1229(85)90069-8. [DOI] [PubMed] [Google Scholar]
  36. Skurkovich S. V., Skorikova A. S., Eremkina E. I. Enhancement by interferon of lymphocyte cytotoxicity in normal individuals to cells of human lymphoblastoid lines. J Immunol. 1978 Sep;121(3):1173–1176. [PubMed] [Google Scholar]
  37. Swaak A. J., Aarden L. A., Statius van Eps L. W., Feltkamp T. E. Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum. 1979 Mar;22(3):226–235. doi: 10.1002/art.1780220304. [DOI] [PubMed] [Google Scholar]
  38. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  39. Tan E. M., Rodnan G. P., Garcia I., Moroi Y., Fritzler M. J., Peebles C. Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. Arthritis Rheum. 1980 Jun;23(6):617–625. doi: 10.1002/art.1780230602. [DOI] [PubMed] [Google Scholar]
  40. Vogt V. M. Purification and further properties of single-strand-specific nuclease from Aspergillus oryzae. Eur J Biochem. 1973 Feb 15;33(1):192–200. doi: 10.1111/j.1432-1033.1973.tb02669.x. [DOI] [PubMed] [Google Scholar]
  41. Weiner H. L., Scribner D. J., Schocket A. L., Moorhead J. W. Increased proliferative response of human peripheral blood lymphocytes to anti-immunoglobulin antibodies in elderly people. Clin Immunol Immunopathol. 1978 Mar;9(3):356–362. doi: 10.1016/0090-1229(78)90107-1. [DOI] [PubMed] [Google Scholar]
  42. Weinstein A., Bordwell B., Stone B., Tibbetts C., Rothfield N. F. Antibodies to native DNA and serum complement (C3) levels. Application to diagnosis and classification of systemic lupus erythematosus. Am J Med. 1983 Feb;74(2):206–216. doi: 10.1016/0002-9343(83)90613-7. [DOI] [PubMed] [Google Scholar]
  43. Weksler M. E. Age-associated changes in the immune response. J Am Geriatr Soc. 1982 Nov;30(11):718–723. doi: 10.1111/j.1532-5415.1982.tb01988.x. [DOI] [PubMed] [Google Scholar]
  44. Whittingham S., Buckley J. D., Mackay I. R. Factors influencing the secondary antibody response to flagellin in man. Clin Exp Immunol. 1978 Nov;34(2):170–178. [PMC free article] [PubMed] [Google Scholar]
  45. Whittingham S., Mathews J. D., Mackay I. R., Stocks A. E., Ungar B., Martin F. I. Diabetes mellitus, autoimmunity, and ageing. Lancet. 1971 Apr 17;1(7703):763–766. doi: 10.1016/s0140-6736(71)91212-8. [DOI] [PubMed] [Google Scholar]

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