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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1989 Oct;48(10):843–850. doi: 10.1136/ard.48.10.843

Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus erythematosus.

N J Goulding 1, M R Podgorski 1, N D Hall 1, R J Flower 1, J L Browning 1, R B Pepinsky 1, P J Maddison 1
PMCID: PMC1003892  PMID: 2554826

Abstract

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kD protein, lipocortin-1. Autoantibodies to lipocortin-1 were measured by enzyme linked immunosorbent assay (ELISA) in 90 healthy subjects and in 63 patients with rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE), 26 with polymyalgia rheumatica, and 13 with chronic airways disease. Sixteen patients with RA receiving prolonged, high steroid doses (prednisolone greater than 7.5 mg/day) had raised IgM antilipocortin-1 levels, while 19 patients with RA untreated with steroids had normal levels. This association was independent of disease activity. In SLE, raised antilipocortin-1 levels were associated with active disease and were independent of steroid treatment. Antilipocortin-1 antibody levels were not raised in patients with polymyalgia rheumatica and chronic airways disease. Thus steroid treatment alone appears insufficient to induce antilipocortin-1 antibodies, unless an underlying autoimmune state is also present. In RA, antilipocortin-1 antibodies may impair anti-inflammatory actions of steroids and render some patients 'steroid resistant'.

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Selected References

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  1. Bird H. A., Esselinckx W., Dixon A. S., Mowat A. G., Wood P. H. An evaluation of criteria for polymyalgia rheumatica. Ann Rheum Dis. 1979 Oct;38(5):434–439. doi: 10.1136/ard.38.5.434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blackwell G. J., Carnuccio R., Di Rosa M., Flower R. J., Parente L., Persico P. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature. 1980 Sep 11;287(5778):147–149. doi: 10.1038/287147a0. [DOI] [PubMed] [Google Scholar]
  3. Carmichael J., Paterson I. C., Diaz P., Crompton G. K., Kay A. B., Grant I. W. Corticosteroid resistance in chronic asthma. Br Med J (Clin Res Ed) 1981 May 2;282(6274):1419–1422. doi: 10.1136/bmj.282.6274.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cupps T. R., Edgar L. C., Thomas C. A., Fauci A. S. Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids. J Immunol. 1984 Jan;132(1):170–175. [PubMed] [Google Scholar]
  5. Davidson F. F., Dennis E. A., Powell M., Glenney J. R., Jr Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids. J Biol Chem. 1987 Feb 5;262(4):1698–1705. [PubMed] [Google Scholar]
  6. Di Rosa M., Flower R. J., Hirata F., Parente L., Russo-Marie F. Anti-phospholipase proteins. Prostaglandins. 1984 Oct;28(4):441–442. doi: 10.1016/0090-6980(84)90232-6. [DOI] [PubMed] [Google Scholar]
  7. Doekes G., Westedt M. L., de Rooy-Dijk H. H., Daha M. R., de Vries E., Cats A. Spontaneous immunoglobulin synthesis by peripheral mononuclear cells in active rheumatoid arthritis. Rheumatol Int. 1986;6(6):263–268. doi: 10.1007/BF00541317. [DOI] [PubMed] [Google Scholar]
  8. Griggs R. C., Condemi J. J., Vaughan J. H. Effect of therapeutic dosages of prednisone on human immunoglobulin G metabolism. J Allergy Clin Immunol. 1972 May;49(5):267–273. doi: 10.1016/0091-6749(72)90094-2. [DOI] [PubMed] [Google Scholar]
  9. Haraoui B., Wilder R. L., Malone D. G., Allen J. B., Katona I. M., Wahl S. M. Immune function in severe, active rheumatoid arthritis: a relationship between peripheral blood mononuclear cell proliferation to soluble antigens and mononuclear cell subset profiles. J Immunol. 1984 Aug;133(2):697–701. [PubMed] [Google Scholar]
  10. Harris E. N., Gharavi A. E., Patel S. P., Hughes G. R. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol. 1987 Apr;68(1):215–222. [PMC free article] [PubMed] [Google Scholar]
  11. Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirata F., del Carmine R., Nelson C. A., Axelrod J., Schiffmann E., Warabi A., De Blas A. L., Nirenberg M., Manganiello V., Vaughan M. Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. Proc Natl Acad Sci U S A. 1981 May;78(5):3190–3194. doi: 10.1073/pnas.78.5.3190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pepinsky R. B., Sinclair L. K., Browning J. L., Mattaliano R. J., Smart J. E., Chow E. P., Falbel T., Ribolini A., Garwin J. L., Wallner B. P. Purification and partial sequence analysis of a 37-kDa protein that inhibits phospholipase A2 activity from rat peritoneal exudates. J Biol Chem. 1986 Mar 25;261(9):4239–4246. [PubMed] [Google Scholar]
  14. Pepinsky R. B., Tizard R., Mattaliano R. J., Sinclair L. K., Miller G. T., Browning J. L., Chow E. P., Burne C., Huang K. S., Pratt D. Five distinct calcium and phospholipid binding proteins share homology with lipocortin I. J Biol Chem. 1988 Aug 5;263(22):10799–10811. [PubMed] [Google Scholar]
  15. Poznansky M. C., Gordon A. C., Douglas J. G., Krajewski A. S., Wyllie A. H., Grant I. W. Resistance to methylprednisolone in cultures of blood mononuclear cells from glucocorticoid-resistant asthmatic patients. Clin Sci (Lond) 1984 Dec;67(6):639–645. doi: 10.1042/cs0670639. [DOI] [PubMed] [Google Scholar]
  16. Poznansky M. C., Gordon A. C., Grant I. W., Wyllie A. H. A cellular abnormality in glucocorticoid resistant asthma. Clin Exp Immunol. 1985 Jul;61(1):135–142. [PMC free article] [PubMed] [Google Scholar]
  17. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  18. ROTSTEIN J., GOOD R. A. Steroid pseudorheumatism. AMA Arch Intern Med. 1957 Apr;99(4):545–555. doi: 10.1001/archinte.1957.00260040045005. [DOI] [PubMed] [Google Scholar]
  19. SLOCUMB C. H. Relative cortisone deficiency simulating exacerbation of arthritis. Bull Rheum Dis. 1952 Oct;3(2):21–22. [PubMed] [Google Scholar]
  20. Seitz M., Hunstein W. Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. Ann Rheum Dis. 1985 Jul;44(7):438–445. doi: 10.1136/ard.44.7.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smiley J. D., Sachs C., Ziff M. In vitro synthesis of immunoglobulin by rheumatoid synovial membrane. J Clin Invest. 1968 Mar;47(3):624–632. doi: 10.1172/JCI105758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Tuchinda M., Newcomb R. W., DeVald B. L. Effect of prednisone treatment on the human immune response to keyhole limpet hemocyanin. Int Arch Allergy Appl Immunol. 1972;42(4):533–544. doi: 10.1159/000230634. [DOI] [PubMed] [Google Scholar]
  24. Wallner B. P., Mattaliano R. J., Hession C., Cate R. L., Tizard R., Sinclair L. K., Foeller C., Chow E. P., Browing J. L., Ramachandran K. L. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature. 1986 Mar 6;320(6057):77–81. doi: 10.1038/320077a0. [DOI] [PubMed] [Google Scholar]

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