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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2002 Apr;61(4):346–350. doi: 10.1136/ard.61.4.346

Influence of prior pregnancies on disease course and cause of death in systemic sclerosis

C Artlett 1, M Rasheed 1, K Russo-Stieglitz 1, H Sawaya 1, S Jimenez 1
PMCID: PMC1754050  PMID: 11874839

Abstract

Background: Microchimerism from fetal or maternal cells transferred during pregnancy has been implicated in the pathogenesis of systemic sclerosis (SSc).

Objective: To determine whether a prior pregnancy influenced disease progression and cause of death in patients with SSc.

Patients and methods: The patients comprised a retrospective study cohort of 111 women with SSc: 78 patients with prior pregnancies (PP) and 33 who were never pregnant (NP), followed up at Thomas Jefferson University. Differences in age at onset, disease subset, organ involvement, cause of death, and type of antinuclear autoantibodies were evaluated statistically, including regression analysis.

Results: The age at onset of SSc in NP patients was 32.0 years compared with 45.7 years in patients with one or two prior pregnancies (p<0.0001), 46.6 years in patients with three or four pregnancies (p<0.0001), and 51.3 years in patients with five to seven pregnancies (p<0.0005). In the 16 patients who had an elective pregnancy termination, 14/16 (87.5%) had diffuse SSc v 2/16 (12.5%) with limited SSc (p<0.0001; odds ratio (OR)=49.0). Of the NP women, 7/30 (23%) died from SSc related causes v 3/78 (4%) women who had pregnancies (p=0.0058; OR=7.6). A carbon monoxide transfer factor (TLCO) of <60% and disease duration >10 years was found in 10/13 (77%) NP patients v 10/23 (43%) patients who had pregnancies (p=0.05; OR=4.7), and a TLCO <50% and disease duration >10 years was identified in 7/13 (54%) NP patients v 6/23 (26%) of the patients who had pregnancies (p=0.09; OR=3.2).

Conclusions: There are differences in the age at onset, clinical course, severity of lung involvement, and cause of death in women who develop SSc before pregnancy compared with those who develop it after pregnancies. The NP patients with SSc had onset of disease at an earlier age, more severe lung involvement, and higher rate of death due to SSc.

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Selected References

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  1. Artlett C. M., Ramos R., Jiminez S. A., Patterson K., Miller F. W., Rider L. G. Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group. Lancet. 2000 Dec 23;356(9248):2155–2156. doi: 10.1016/s0140-6736(00)03499-1. [DOI] [PubMed] [Google Scholar]
  2. Artlett C. M., Smith J. B., Jimenez S. A. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med. 1998 Apr 23;338(17):1186–1191. doi: 10.1056/NEJM199804233381704. [DOI] [PubMed] [Google Scholar]
  3. Artlett C. M., Smith J. B., Jimenez S. A. New perspectives on the etiology of systemic sclerosis. Mol Med Today. 1999 Feb;5(2):74–78. doi: 10.1016/s1357-4310(98)01405-1. [DOI] [PubMed] [Google Scholar]
  4. Artlett C. M., Welsh K. I., Black C. M., Jimenez S. A. Fetal-maternal HLA compatibility confers susceptibility to systemic sclerosis. Immunogenetics. 1997;47(1):17–22. doi: 10.1007/s002510050321. [DOI] [PubMed] [Google Scholar]
  5. Bianchi D. W., Zickwolf G. K., Weil G. J., Sylvester S., DeMaria M. A. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):705–708. doi: 10.1073/pnas.93.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Black C. M., Stevens W. M. Scleroderma. Rheum Dis Clin North Am. 1989 May;15(2):193–212. [PubMed] [Google Scholar]
  7. Deneys V., De Bruyere M. Immunological tolerance of the fetal allograft: efficacy of immunotherapy and IL-4 and TNF alpha serum levels in recurrent abortion. Transplant Proc. 1997 Aug;29(5):2467–2469. doi: 10.1016/s0041-1345(97)00451-x. [DOI] [PubMed] [Google Scholar]
  8. Fagundus D. M., Leroy E. C. Cytokines and systemic sclerosis. Clin Dermatol. 1994 Jul-Sep;12(3):407–417. doi: 10.1016/0738-081x(94)90293-3. [DOI] [PubMed] [Google Scholar]
  9. Fleischmajer R., Perlish J. S., Reeves J. R. Cellular infiltrates in scleroderma skin. Arthritis Rheum. 1977 May;20(4):975–984. doi: 10.1002/art.1780200410. [DOI] [PubMed] [Google Scholar]
  10. Goplerud C. P. Scleroderma. Clin Obstet Gynecol. 1983 Sep;26(3):587–591. [PubMed] [Google Scholar]
  11. Hartwell D., Levine J., Fenton M., Francis C., Leslie C., Beller D. Cytokine dysregulation and the initiation of systemic autoimmunity. Immunol Lett. 1994 Dec;43(1-2):15–21. doi: 10.1016/0165-2478(94)00144-8. [DOI] [PubMed] [Google Scholar]
  12. JOHNSON T. R., BANNER E. A., WINKELMANN R. K. SCLERODERMA AND PREGNANCY. Obstet Gynecol. 1964 Mar;23:467–469. [PubMed] [Google Scholar]
  13. Janin-Mercier A., Devergie A., Van Cauwenberge D., Saurat J. H., Bourges M., Lapiere C. M., Gluckman E. Immunohistologic and ultrastructural study of the sclerotic skin in chronic graft-versus-host disease in man. Am J Pathol. 1984 May;115(2):296–306. [PMC free article] [PubMed] [Google Scholar]
  14. Jimenez S. A., Hitraya E., Varga J. Pathogenesis of scleroderma. Collagen. Rheum Dis Clin North Am. 1996 Nov;22(4):647–674. doi: 10.1016/s0889-857x(05)70294-5. [DOI] [PubMed] [Google Scholar]
  15. Jiménez S. A. Cellular immune dysfunction and the pathogenesis of scleroderma. Semin Arthritis Rheum. 1983 Aug;13(1 Suppl 1):104–113. doi: 10.1016/0049-0172(83)90029-x. [DOI] [PubMed] [Google Scholar]
  16. Kahaleh M. B., LeRoy E. C. Interleukin-2 in scleroderma: correlation of serum level with extent of skin involvement and disease duration. Ann Intern Med. 1989 Mar 15;110(6):446–450. doi: 10.7326/0003-4819-110-6-446. [DOI] [PubMed] [Google Scholar]
  17. Lally E. V., Jimenez S. A., Kaplan S. R. Progressive systemic sclerosis: mode of presentation, rapidly progressive disease course, and mortality based on an analysis of 91 patients. Semin Arthritis Rheum. 1988 Aug;18(1):1–13. doi: 10.1016/0049-0172(88)90030-3. [DOI] [PubMed] [Google Scholar]
  18. Lambert I. A., Suitters A. J., Janossy G., Thomas J. A., Palmer S., Gordon Smith E. Lymphoid infiltrates in skin in graft-versus-host disease. Lancet. 1981 Dec 12;2(8259):1352–1352. doi: 10.1016/s0140-6736(81)91378-7. [DOI] [PubMed] [Google Scholar]
  19. Launay D., Hebbar M., Hatron P. Y., Michon-Pasturel U., Queyrel V., Hachulla E., Devulder B. Relationship between parity and clinical and biological features in patients with systemic sclerosis. J Rheumatol. 2001 Mar;28(3):509–513. [PubMed] [Google Scholar]
  20. Lawley T. J., Peck G. L., Moutsopoulos H. M., Gratwohl A. A., Deisseroth A. B. Scleroderma, Sjögren-like syndrome, and chronic graft-versus-host disease. Ann Intern Med. 1977 Dec;87(6):707–709. doi: 10.7326/0003-4819-87-6-707. [DOI] [PubMed] [Google Scholar]
  21. LeRoy E. C., Black C., Fleischmajer R., Jablonska S., Krieg T., Medsger T. A., Jr, Rowell N., Wollheim F. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb;15(2):202–205. [PubMed] [Google Scholar]
  22. LeRoy E. C. Systemic sclerosis. A vascular perspective. Rheum Dis Clin North Am. 1996 Nov;22(4):675–694. doi: 10.1016/s0889-857x(05)70295-7. [DOI] [PubMed] [Google Scholar]
  23. Liegeois A., Gaillard M. C., Ouvre E., Lewin D. Microchimerism in pregnant mice. Transplant Proc. 1981 Mar;13(1 Pt 2):1250–1252. [PubMed] [Google Scholar]
  24. Lin H., Mosmann T. R., Guilbert L., Tuntipopipat S., Wegmann T. G. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol. 1993 Nov 1;151(9):4562–4573. [PubMed] [Google Scholar]
  25. Maloney S., Smith A., Furst D. E., Myerson D., Rupert K., Evans P. C., Nelson J. L. Microchimerism of maternal origin persists into adult life. J Clin Invest. 1999 Jul;104(1):41–47. doi: 10.1172/JCI6611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nelson J. L., Furst D. E., Maloney S., Gooley T., Evans P. C., Smith A., Bean M. A., Ober C., Bianchi D. W. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet. 1998 Feb 21;351(9102):559–562. doi: 10.1016/S0140-6736(97)08357-8. [DOI] [PubMed] [Google Scholar]
  27. Nelson J. L. Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum. 1996 Feb;39(2):191–194. doi: 10.1002/art.1780390203. [DOI] [PubMed] [Google Scholar]
  28. Okano Y. Antinuclear antibody in systemic sclerosis (scleroderma). Rheum Dis Clin North Am. 1996 Nov;22(4):709–735. doi: 10.1016/s0889-857x(05)70297-0. [DOI] [PubMed] [Google Scholar]
  29. Piccinni M. P., Scaletti C., Maggi E., Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol. 2000 Sep 1;109(1):30–33. doi: 10.1016/s0165-5728(00)00299-x. [DOI] [PubMed] [Google Scholar]
  30. Postlethwaite A. E. Connective tissue metabolism including cytokines in scleroderma. Curr Opin Rheumatol. 1993 Nov;5(6):766–772. doi: 10.1097/00002281-199305060-00012. [DOI] [PubMed] [Google Scholar]
  31. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980 May;23(5):581–590. doi: 10.1002/art.1780230510. [DOI] [PubMed] [Google Scholar]
  32. Reinhard G., Noll A., Schlebusch H., Mallmann P., Ruecker A. V. Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes. Biochem Biophys Res Commun. 1998 Apr 28;245(3):933–938. doi: 10.1006/bbrc.1998.8549. [DOI] [PubMed] [Google Scholar]
  33. Shimaoka Y., Hidaka Y., Tada H., Nakamura T., Mitsuda N., Morimoto Y., Murata Y., Amino N. Changes in cytokine production during and after normal pregnancy. Am J Reprod Immunol. 2000 Sep;44(3):143–147. doi: 10.1111/j.8755-8920.2000.440303.x. [DOI] [PubMed] [Google Scholar]
  34. Siimes M. A., Johansson E., Rapola J. Scleroderma-like graft-versus-host disease as late consequence of bone-marrow grafting. Lancet. 1977 Oct 15;2(8042):831–832. doi: 10.1016/s0140-6736(77)90772-3. [DOI] [PubMed] [Google Scholar]
  35. Silman A. J., Black C. Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study. Ann Rheum Dis. 1988 Jun;47(6):441–444. doi: 10.1136/ard.47.6.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Silman A. J. Pregnancy and scleroderma. Am J Reprod Immunol. 1992 Oct-Dec;28(3-4):238–240. doi: 10.1111/j.1600-0897.1992.tb00802.x. [DOI] [PubMed] [Google Scholar]
  37. Slate W. G., Graham A. R. Scleroderma and pregnancy. Am J Obstet Gynecol. 1968 Jun 1;101(3):335–341. doi: 10.1016/0002-9378(68)90059-8. [DOI] [PubMed] [Google Scholar]
  38. Steen V. D. Scleroderma and pregnancy. Rheum Dis Clin North Am. 1997 Feb;23(1):133–147. doi: 10.1016/s0889-857x(05)70319-7. [DOI] [PubMed] [Google Scholar]
  39. Suzumori K., Adachi R., Okada S., Narukawa T., Yagami Y., Sonta S. Fetal cells in the maternal circulation: detection of Y-sequence by gene amplification. Obstet Gynecol. 1992 Jul;80(1):150–154. [PubMed] [Google Scholar]

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