Skip to main content

Advertisement

Log in

Microchimerism and hla relationships of pregnancy: Implications for autoimmune diseases

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

The application of molecular techniques to the study of human pregnancy has resulted in knowledge that the placenta is only a relative barrier to traffic of fetal and maternal cells. Moreover, long-term persistence of fetal cells in the maternal circulation and maternal cells in her progeny have been described. Harboring of cells from another individual is referred to as chimerism and microchimerism indicates low levels of non-host cells. The clinical features of a known condition of human chimerism, chronic graft-versus-host disease that occurs after stem cell transplantation, resemble spontaneously occurring autoimmune diseases including systemic sclerosis, Sjögren’s syndrome, primary biliary cirrhosis, and sometimes myositis and systemic lupus. A critical determinant of chronic graft-versus-host disease is the HLA relationship of donor and host cells. When considered together, these observations have led to a new area of research investigating whether microchimerism and HLA-relationships are involved in the pathogenesis of some autoimmune diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Bianchi DW: Current knowledge about fetal blood cells in the maternal circulation. J Perinat Med 1998, 16:175–185.

    Google Scholar 

  2. Hall JM, Lingenfelter P, Adams SL, et al.: Detection of maternal cells in human umbilical cord blood using fluorescence in situ hybridization. Blood 1995, 86:2829–2832.

    PubMed  CAS  Google Scholar 

  3. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA: Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci USA 1996, 93:705–708. A study of healthy women in which the seminal observation was reported that fetal cells persist for decades after pregnancy completion.

    Article  PubMed  CAS  Google Scholar 

  4. Maloney S, Smith AG, Furst DE, et al.: Microchimerism of maternal origin persists into adult life. J Clin Invest 1999, 104:41–47. The first description of long-term persistence of maternal microchimerism in immunocompetent individuals.

    Article  PubMed  CAS  Google Scholar 

  5. De Moor G, De Bock G, Noens L, De Bic S: A new case of human chimerism detected after pregnancy: 46,XY karyotype in the lymphocytes of a woman. Acta Clin Belg 1988, 43:231–235.

    PubMed  Google Scholar 

  6. Lee TH, Paglieroni T, Ohto H, Holland PV, Busch MP: Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. Blood 1999, 93:3127–3139. Description of long-term persistence of donor cells in trauma patients who have received multiple transfusions.

    PubMed  CAS  Google Scholar 

  7. Nelson JL: Maternal-fetal immunology and autoimmune disease. Is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum 1996, 39:191–194. Presentation of the hypothesis that non-host cells are involved in the pathogenesis of autoimmune disease, providing the rationale for the hypothesis and the corollary hypothesis that HLA compatibility of a child increases risk of subsequent autoimmune disease in the mother.

    Article  PubMed  CAS  Google Scholar 

  8. Thomas MR, Williamson R, Craft I, Yazdani N, Rodeck CH: Y chromosome sequence DNA amplified from peripheral blood of women in early pregnancy. Lancet 1994, 343:413–414.

    Article  PubMed  CAS  Google Scholar 

  9. Lo YMD, Lau TK, Chan LYS, Leung TN, Chang AMZ: Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem 2000, 46:1301–1309.

    PubMed  CAS  Google Scholar 

  10. Lo YMD, Lo ESF, Watson N, et al.: Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood 1996, 88:4390–4395. Describes the application of PCR-based techniques and documents traffic of cells during human pregnancy from fetus to mother and mother to fetus.

    PubMed  CAS  Google Scholar 

  11. Petit T, Dommergues M, Socie G, et al.: Detection of maternal cells in human fetal blood during the third trimester of pregnancy using allele-specific PCR amplification. Br J Haematol 1997, 100:767–771.

    Article  Google Scholar 

  12. Lo ESF, Lo YMD, Hjelm NM, Thilaganathan B: Transfer of nucleated maternal cells into fetal circulation during the second trimester of pregnancy [letter]. Br J Haematol 1998, 100:605–606.

    Article  PubMed  CAS  Google Scholar 

  13. Piotrowski P, Croy BA: Maternal cells are widely distributed in murine fetuses in utero. Biol Reprod 1996, 54:1103–1110. Maternal cells were widely distributed in immunodeficient fetuses and were routinely found in the bone marrow of immune competent fetuses.

    Article  PubMed  CAS  Google Scholar 

  14. Pollack MS, Kirpatrick D, Kapoor N, Dupont B, O’Reilly RJ: Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. N Engl J Med 1982, 307:662–666.

    Article  PubMed  CAS  Google Scholar 

  15. Shulman HM, Sullivan KM: Graft-versus-host disease. Auto and allo immunity after bone marrow transplantation. Concepts Immunopathol 1988, 6:141–165.

    PubMed  CAS  Google Scholar 

  16. Urbano-Marquez A, Estruch R, Grau J, et al.: Inflammatory myopathy associated with chronic graft-versus-host disease. Neurology 1986, 36:1091–1093.

    PubMed  CAS  Google Scholar 

  17. Anasetti C, Rybka W, Sullivan KM, Banaji M, Slichter SJ: Graft-vs-host disease is associated with autoimmune-like thrombocytopenia. Blood 1989, 73:1054–1058.

    PubMed  CAS  Google Scholar 

  18. Klumpp TR, Herman JH: Autoimmune neutropenia after bone marrow transplantation. Blood 1993, 82:1035.

    PubMed  CAS  Google Scholar 

  19. Smith C, Norberg R, Moller G, Lonnqvist B, Hammarstrom L: Autoantibody formation after bone marrow transplantation. Eur Neurol 1989, 29:128–134.

    PubMed  CAS  Google Scholar 

  20. Lister J, Messner H, Keysonte E, Miller R, Fritzler M: Autoantibody analysis of patients with graft versus host disease. J Clin Lab Immunol 1987, 24:19–20. Includes the description of antibodies to dsDNA in patients with graft-versus-host disease.

    PubMed  CAS  Google Scholar 

  21. Nelson JL, Furst DE, Maloney S, et al.: Microchimerism and HLA-compatible relationships of pregnancy in SSc. Lancet 1998, 351:559–562. First report of microchimerism in patients with SSc showing fetal microchimerism was quantitatively greater in women with SSc than in healthy women. HLA-DRB1 compatibility of a previously born child was identified as a risk factor for subsequent SSc in the mother.

    Article  PubMed  CAS  Google Scholar 

  22. Artlett CM, Smith JB, Jimenez SA: Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 1998, 338:1186–1191. A significant difference in the frequency of microchimerism in DNA extracted from skin was found in DNA extracted from biopsies of SSc patients compared with controls.

    Article  PubMed  CAS  Google Scholar 

  23. Murata H, Nakauchi H, Sumida T: Microchimerism in Japanese women patients with systemic sclerosis. Lancet 1999, 354:220.

    Article  PubMed  CAS  Google Scholar 

  24. Evans PC, Lambert N, Maloney S, et al.: Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood 1999, 93:1–6.

    Google Scholar 

  25. McMilin KD, Johnson RL: HLA homozygosity and the risk of related-donor transfusion-associated graft-versus-host disease. Transfus Med Rev 1993, 7:37–41.

    PubMed  CAS  Google Scholar 

  26. Lambert NC, Evans PC, Hashizumi TL, Maloney S, Gooley T, Furst DE, Nelson JL.: Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity. J Immunol 2000, 164:5545–5548.

    PubMed  CAS  Google Scholar 

  27. Aractingi S, Berkane N, Bertheau P, et al.: Fetal DNA in skin of polymorphic eruptions of pregnancy. Lancet 1999, 352:1898–1901. An elegant and carefully conducted study in which pregnant women suffering from a skin disease were found to have microchimerism in skin biopsy samples that was not found in matched controls.

    Article  Google Scholar 

  28. Tanaka A, Lindor K, Gish R, et al.: Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis. Hepatology 1999, 30:833–838.

    Article  PubMed  CAS  Google Scholar 

  29. Negishi I, Endo Y, Maebashi OI: Identification of fetal lymphocytes infiltrating in the salivary glands of patients with Sjögren’s syndrome [abstract]. Arthritis Rheum 1999, 42:S140.

    Google Scholar 

  30. Reed AM, Picornell YJ, Harwood A, Kredich DW: Chimerism in children with juvenile dermatomyositis [letter]. Lancet 2000, 356:2156–2157. A study of patients with juvenile dermatomyositis with a strong study design using unaffected siblings as controls. Maternal microchimerism was found more often in patients than in unaffected siblings.

    Article  PubMed  CAS  Google Scholar 

  31. Artlett CM, Ramos R, Jiminez SA, et al.: Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies [letter]. Lancet 2000, 356:2155–2156. A study of patients with juvenile idiopathic inflammatory myopathy in whom maternal microchimerism was found more often than in controls.

    Article  PubMed  CAS  Google Scholar 

  32. Christner PJ, Artlett CM, Conway RF, Jiminez SA: Increased numbers of microchimeric cells of fetal origin are associated with dermal fibrosis in mice following injection of vinyl chloride. Arthritis Rheum 2000, 43:2598–2605. An experimental model of SSc that brings together microchimerism, pathologic changes in tissues and the exogenous agent and vinyl chloride, in disease pathogenesis.

    Article  PubMed  CAS  Google Scholar 

  33. Nelson JL, Hughes KA, Smith AG, et al.: Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 1993, 329:466–471.

    Article  PubMed  CAS  Google Scholar 

  34. Mullinax F: Chimerism and autoimmunity. In Proceedings of the Fourth ASEAN Congress. Rheumatology 1993:39–40. A patient with systemic lupus and a patient with scleroderma are described in which chimerism was suspected to be involved in the disease.

  35. Gleichman E, Van Elven H, Van der Veen JP: A systemic lupus erythematosus (SLE)-like disease in mice induced by abnormal T-B cell cooperation. Eur J Immunol 1982, 12:152–155.

    Article  Google Scholar 

  36. Portanova JP, Claman HN, Kotzin BL: Autoimmunization in murine graft-vs-host disease, I: Selective production of antibodies to histones and DNA. J Immunol 1985, 135:3580–3586.

    Google Scholar 

  37. Portanova JP, Ebling FM, Hammond WS, Hahn BH, Kotzin BL: Allogeneic MHC antigen requirements for lupus-like autoantibody production and nephritis in murine graft-vs-host disease. J Immunol 1988, 141:3370–3376.

    PubMed  CAS  Google Scholar 

  38. Nelson JL: Microchimerism and autoimmune disease. N Engl J Med 1998, 338:1224–1225.

    Article  PubMed  CAS  Google Scholar 

  39. Buyon JP: Neonatal lupus syndromes. In Systemic Lupus rythematosus, edn 3. Edited by Lahita R. San Diego: Academic Press; 1998:337–359.

    Google Scholar 

  40. Claas FHJ, Gijbels Y, van der Velden-de Munck J, van Rood JJ: Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life. Science 1988, 241:1815–1817.

    Article  PubMed  CAS  Google Scholar 

  41. Holzgreve W, Ghezzi F, Di Naro E, et al.: Disturbed feto-maternal cell traffic in preeclampsia. Obstet Gynecol 1998, 91:669–672.

    Article  PubMed  CAS  Google Scholar 

  42. Nelson JL, Tsao B, Hahn B, et al.: Microchimerism: a new etiology for autoimmune disease? FASEB J 1999, 13:A958.

    Google Scholar 

  43. Lambert N, Distler O, Muller-Ladner U, et al.: HLA DQA1*0501 is associated with diffuse systemic sclerosis in men. Arthritis Rheum 2000, 43:2005–2010.

    Article  PubMed  CAS  Google Scholar 

  44. Starzl TE, Demetris AJ, Murase N, et al.: The lost chord: microchimerism and allograft survival. Immunol Today 1996, 17:577–584.

    Article  PubMed  CAS  Google Scholar 

  45. Hakim FT, Mackall CL: The immune system: effector and target of graft-versus-host disease In Graft-vs-Host Disease, edn 2. Edited by Ferrara JL, Deeg HJ, Burakof ST. New York: Marcel Dekker; 1997:274–289.

    Google Scholar 

  46. Suzuki K, Narita T, Yui R, Asakura H, Fujiwara M: Mechanism of the induction of autoimmune disease by graft-versus-host reaction. Role of CD8+ cells in the development of hepatic and ductal lesions induced by CD4+ cells in MHC class I plus II different host. Lab Invest 1994, 70:609–619.

    PubMed  CAS  Google Scholar 

  47. Sayegh MH, Carpenter CB: Role of indirect allorecognition in allograft rejection. Int Rev Immunol 1996, 13:221–229.

    PubMed  CAS  Google Scholar 

  48. Miller RG: The veto phenomenon and T-cell regulation. Immunol Today 1986, 7:112–114.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nelson, J.L. Microchimerism and hla relationships of pregnancy: Implications for autoimmune diseases. Curr Rheumatol Rep 3, 222–229 (2001). https://doi.org/10.1007/s11926-001-0022-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-001-0022-5

Keywords

Navigation