Otoimmün tiroid hastalıkları ve fetüse ait mikrokimerizm

Öz

Gebelik esnasında, plasenta yoluyla, hematopoetik hücrelerin iki taraflı geçişi olmaktadır. Fetüse ait hücrelerin, anne kanına ulaştıkları ve annenin çeşitli dokularına nüfuz ettikleri iyi bilinmektedir fetüse ait mikrokimerizm . Bir bireyde, genetik olarak farklı bir bireyden alınmış az miktarda DNA ya da hücrenin var olma durumuna “mikrokimerizm” denmektedir. İnsanlarda, otoimmün tiroid hastalıklarının OTH seyir ve ciddiyetinin, gebelikten etkilendiği iyi bilinmektedir; gebelik esnasında OTH’nın baskılanıp, doğum sonrası dönemde ise başlaması ya da alevlenmesi buna bir kanıttır. Gebelik esnasında, tiroid otoantikorları ve Graves hastalığı, baskılanma eğiliminde iken; kadınların yüksek bir oranı , otoimmün Hashimoto’s tiroidite ya da Graves hastalığına doğumdan 3-12 hafta sonra yakalanmaktadırlar. Ek olarak, OTH, doğurganlığı ve gebeliğin akibetini de etkilemekte ve fetüs kayıplarına yol açabilmektedir. Ancak, OTH’nın bu etkilerinin mekanizması henüz tam olarak anlaşılamamıştır. Otoimmün hastalıklarla, kronik graft-versus-host reaksiyonu arasındaki bazı klinik benzerlikler, kadınlarda çocuk sahibi olma dönemini takiben otoimmün hastalıkların artmış insidansı ve mikrokimerizmin anne kanı ya da dokularında uzun dönem varlığını sürdürmesi, otoimmün hastalıkların patogenezinde mikrokimerizmin rol oynayabileceği hipotezini ortaya çıkarmıştır. Bu derlemede, OTH’nın üzerinde mikrokimerizmin muhtemel rolü hakkında en son bilgilere yer verilmiştir

Anahtar Kelimeler

• Gebelik,Graves hastalığı,Hashimoto tiroiditi,mikrokimerizm,otoimmün tiroid hastalıkları

Autoimmune thyroid diseases and fetal microchimerism

Öz

During pregnancy, bi-directional trafficking of hematopoietic cells occurs through the placenta. Fetal cells are known to reach the maternal circulation and infiltrate a variety of tissues fetal microchimerism . The presence of a small population of cells or DNA in one individual that derives from another genetically distinct person is referred to as microchimerism. In humans, the course and severity of the autoimmune thyroid diseases AITD is well known to beaffected by pregnancy as evidenced by disease suppression during pregnancy and initiation / exacerbation in the postpartum period. Although thyroid autoantibodiesand Graves’ disease itself tend to be suppressed duringpregnancy, a high percentage 8–10 % of women developautoimmune Hashimoto’s thyroiditis or Graves’disease 3–12 months after delivery. Furthermore, AITD affect both fertility and pregnancy outcome and cause fetal loss. However, the mechanisms of this influence have not been fully understood. The clinical similarities between some features of autoimmune diseases and the chronic graft versus host disease, the increased incidence of autoimmune diseases in women after childbearing age, and the long-term persistence of microchimerism in maternal blood / tissues have raised the hypothesis that microchimerism could be involved in the pathogenesis of autoimmune diseases. Here we have reviewed recent information on the possible role of fetal microchimerism in autoimmune thyroid disease

Anahtar Kelimeler

• Autoimmune thyroid diseases,Hashimoto’s thyroiditis,Graves’ disease,microchimerism,pregnancy

Kaynakça

1. 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 U S A. 1996; 93(2):705-8.
2. Aractingi S, Uzan S, Dausset J, Carosella ED. Microchimerism in human diseases. Immunol Today. 2000; 21(3):116-8.
3. Shulman LP. Fetal cells in maternal blood. Curr Womens Health Rep. 2003; 3(1):47-54.
4. Srivatsa B, Srivatsa S, Johnson KL, Bianchi DW. Maternal cell microchimerism in newborn tissues. J Pediatr. 2003; 142(1):31- 5.
5. 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; 343:413–4.
6. Sarkar K, Miller FW. Possible roles and determinants of microchimerism in autoimmune and other disorders. Autoimmun Rev. 2004; 3(6):454-63.
7. Davies TF. The thyroid immunology of the postpartum period. Thyroid. 1999; 9:675–84. 8. Turco AE, Bambara LM. Pregnancy, microchimerism and autoimmunity: an update. Lupus. 2004; 13(9):659-60.
8. Ando T, Davies TF. Postpartum Autoimmune Thyroid Disease: The Potential Role of Fetal Microchimerism . The Journal of Clinical Endocrinology & Metabolism. 2003; 88(7):2965-71.

9. Nader S. Thyroid disease and other endocrine disorders in pregnancy. Obstet Gynecol Clin North Am. 2004; 31(2):257-85.
10. Stagnaro-Green A. Postpartum thyroiditis. Best Pract Res Clin Endocrinol Metab. 2004; 18(2):303-16.
11. Kung AW, Jones BM. A change from stimulatory to blocking antibody activity in Graves’ disease during pregnancy. J Clin Endocrinol Metab. 1998; 83:514–8.
12. Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Wallenstein S, et al. A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction. J Clin Endocrinol Metab. 1992; 74:645–53.
13. Jansson R, Dahlberg PA, Winsa B, Meirik O, Safwenberg J, et al. The postpartum period constitutes an important risk for the development of clinical Graves’ disease in young women. Acta Endocrinol (Copenh). 1987; 116:321–5.
14. Amino N, Tada H, Hidaka Y. Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease. Thyroid. 1999; 9:705–13.
15. Abs R, Martin M, Blockx P. Changes in serum thyroid hormone autoantibody concentrations during pregnancy: a case report. Horm Res. 1991; 35(5):205-7.
16. Amino N, Mori H, Iwatani Y, Tanizawa O, Kawashima M, et al. High prevalence of transient post- partum thyrotoxicosis and hypothyroidism. N Engl J Med. 1982; 306:849–52.
17. Ando T, Davies TF. Postpartum Autoimmune Thyroid Disease: The Potential Role of Fetal Microchimerism . The Journal of Clinical Endocrinology & Metabolism. 2003; 88(7):2965-71.
18. Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet. 2001; 358(9298):2034-8.
19. Dayan CM, Daniels GH. Chronic autoimmune thyreoiditis. N Engl J Med. 1996; 335(2):99-107.
20. Karabinas CD. Thyroid disorders and pregnancy. J Obstet Gynaecol. 1998; 18(6):509-15.
21. Klintschar M, Schwaiger P, Mannweiler S, Regauer S, Kleiber M. Evidence of fetal microchimerism in Hashimoto's thyroiditis. J Clin Endocrinol Metab. 2001; 86(6):2494-8.
22. Barbesino G, Tomer Y, Concepcion E, Davies TF, Greenberg DA. Linkage analysis of candidate genes in autoimmune thyroid disease. I. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease. J Clin Endocrinol Metab. 1998; 83:1580–4.
23. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Graves' disease. J Clin Endocrinol Metab. 2002; 87(7):3315-20.
24. Renne C, Ramos Lopez E, Steimle- Grauer SA, Ziolkowski P, Pani MA, et al. Thyroid fetal male microchimerisms in mothers with thyroid disorders: presence of Y- chromosomal immunofluorescence in thyroid-infiltrating lymphocytes is more prevalent in Hashimoto's thyroiditis and Graves' disease than in follicular adenomas. J Clin Endocrinol Metab. 2004; 89(11):5810-4.
25. Imaizumi M, Pritsker A, Unger P, Davies TF. Intrathyroidal fetal microchimerism in pregnancy and postpartum. Endocrinology. 2002; 143:247–253.7. Ohtsuka T, Miyamoto Y, Yamakage A, Yamazaki S. Quantitative analysis of microchimerism in systemic sclerosis skin tissue. Arch Dermatol Res. 2001; 293(8):387-91.
26. Lambert NC, Erickson TD, Yan Z, Pang JM, Guthrie KA, et al. Quantification of maternal microchimerism by HLA-specific real-time polymerase chain reaction: studies of healthy women and women with scleroderma. Arthritis Rheum. 2004; 50(3):906- 14.
27. Endo Y, Negishi I, Ishikawa O. Possible contribution of microchimerism to the pathogenesis of Sjögren's syndrome. Rheumatology (Oxford). 2002 ;41(5):490-5.
28. Fanning PA, Jonsson JR, Clouston AD, Edwards-Smith C, Balderson GA, et al. Detection of male DNA in the liver of female patients with primary biliary cirrhosis. J Hepatol. 2000; 33(5):690-5.
29. Abbud Filho M, Pavarino-Bertelli EC, Alvarenga MP, Fernandes IM, Toledo RA, et al. Systemic lupus erythematosus and microchimerism in autoimmunity. Transplant Proc. 2002; 34(7):2951-2.
30. 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(17):1186-91.
31. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, et al. Microchimerism and HLA- compatible relationships of pregnancy in scleroderma. Lancet. 1998; 351(9102):559-62.
32. Artlett CM, Cox LA, Ramos RC, Dennis TN, Fortunato RA, et al. Increased microchimeric CD4+ T lymphocytes in peripheral blood from women with systemic sclerosis. Clin Immunol. 2002; 103(3 Pt 1):303-8.
33. Lambert NC, Evans PC, Hashizumi TL, et al. Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity. J Immunol. 2000; 164:5545-8.
34. Lambert NC, Stevens AM, Tylee TS, Erickson TD, Furst DE, Nelson JL. From the simple detection of microchimerism in patients with autoimmune diseases to its implications in pathogenesis. Ann N Y Acad Sci. 2001; 945:164-71.
35. Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW. Microchimerism in a female patient with systemic lupus erythematosus. Arthritis Rheum. 2001; 44:2107– 11.
36. Kuroki M, Okayama A, Nakamura S, Sasaki T, Murai K, et al. Detection of maternal-fetal microchimerism in the inflammatory lesions of patients with Sjogren’s syndrome. Ann Rheum Dis. 2002; 61:1041–6.
37. Tanaka A, Lindor K, Gish R, Batts K, Shiratori Y, et al. Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis. Hepatology. 1999; 30:833–8.
38. Miyashita Y, Ono M, Ono M, Ueki H, Kurasawa K. Y chromosome microchimerism in rheumatic autoimmune disease. Ann Rheum Dis. 2000; 59: 655–6.