Preview

Problems of Endocrinology

Advanced search

The role of microchimerism in the development of endocrine diseases (using autoimmune thyroid diseases and type 1 diabetes mellitus as examples)

https://doi.org/10.14341/probl13636

Abstract

Microchimerism — the phenomenon of the presence of genetically foreign cells within the body — holds significant interest for endocrinology. It develops as a result of transplacental cell exchange during pregnancy (fetal and maternal microchimeric cells) or iatrogenic interventions and may play an important role in the development of autoimmune endocrine diseases. The greatest amount of data has been accumulated regarding thyroid diseases: fetal microchimeric cells are detected in 38–83% of cases of autoimmune thyroiditis and Graves’ disease, with their levels correlating with the activity of the autoimmune process. Three main hypotheses have been proposed regarding their involvement in pathogenesis: initiation of a "graft-versus-host" reaction postpartum, molecular mimicry with thyroid antigens, or passive accumulation in inflammatory foci.

In type 1 diabetes mellitus, studies focus on maternal microchimeric cells, which are found in the pancreas of patients and can differentiate into β-cells; however, their pathogenic role remains controversial. Modern methods for detecting microchimeric cells — such as polymerase chain reaction (PCR) and immunofluorescent hybridization in situ (FISH) — are highly sensitive but require standardization. Promising research directions include studying the influence of HLA compatibility, long-term dynamics of microchimeric cells, and their potential therapeutic applications. Addressing these issues could lead to a revision of current understanding of the pathogenesis of endocrine diseases and the development of new treatment approaches.

About the Authors

M. V. Alaverdova
Endocrinology research centre
Russian Federation

Mariya V. Alaverdova,

11 Dm. Ulyanova street, 117292, Moscow



E. A. Troshina
Endocrinology research centre
Russian Federation

Ekaterina A. Troshina - MD, PhD, professor,

11 Dm. Ulyanova street, 117292, Moscow



References

1. Malinska N, Grobarova V, Knizhkova K, Cherny Yu. Maternal-fetal microchimerism: influence on the immune development of offspring and transgenerational immune memory. // Physiol Res. 2024;73(3):315-332 (In Russ.). doi: https://doi.org/10.33549/physiolres.935296

2. Lepez T, Vandewoestyne M, Hussain S, Van Nieuwerburgh F, Poppe K, Velkeniers B, et al. Fetal microchimeric cells in blood of women with an autoimmune thyroid disease. PLoS One. 2011;6:e29646. doi: http://dx.doi.org/10.1371/journal.pone.0029646

3. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Graves’ disease. J Clin Endocrinol Metab. 2002;87:3315-20 doi: http://dx.doi.org/10.1210/jc.87.7.3315

4. Renné C, Ramos Lopez E, Steimle-Grauer SA, Ziolkowski P, Pani MA, Luther C, 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;89:5810-4. doi: http://dx.doi.org/10.1210/jc.2004-1049

5. Laura Fugazzola, Valentina Cirello, Paolo Beck-Peccoz. Microchimerism and Endocrine Disorders. The Journal of Clinical Endocrinology & Metabolism. 2012;97(5):1452–1461 doi: https://doi.org/10.1210/jc.2011-3160

6. Lambert NC, Pang JM, Yan Z, Erickson TD, Stevens AM, Furst DE, et al. Male microchimerism in women with systemic sclerosis and healthy women who have never given birth to a son. Ann Rheum Dis. 2005;64:845-8 doi:http://dx.doi.org/10.1136/ard.2004.029314.

7. Bloch EM, Reed WF, Lee TH, Montalvo L, Shiboski S, Custer B, et al. Male microchimerism in peripheral blood leukocytes from women with multiple sclerosis. Chimerism. 2011;2:6-10 doi: http://dx.doi.org/10.4161/chim.15151

8. Ohtsuka T, Miyamoto Y, Yamakage A, Yamazaki S. Quantitative analysis of microchimerism in systemic sclerosis skin tissue. Arch Dermatol Res. 2001;293:387-91 doi: http://dx.doi.org/10.1007/s004030100245

9. McNallan KT, Aponte C, el-Azhary R, Mason T, Nelson AM, Paat JJ, et al. Immunophenotyping of chimeric cells in localized scleroderma. Rheumatology (Oxford). 2007;46:398-402 doi: http://dx.doi.org/10.1093/rheumatology/kel297.

10. Cha D, Khosrotehrani K, Kim Y, Stroh H, Bianchi DW, Johnson KL. Cervical cancer and microchimerism. Obstet Gynecol. 2003;102:774-81 doi: http://dx.doi.org/10.1016/S0029-7844(03)00615-X.

11. Fanning PA, Jonsson JR, Clouston AD, Edwards-Smith C, Balderson GA, Macdonald GA, et al. Detection of male DNA in the liver of female patients with primary biliary cirrhosis. J Hepatol. 2000;33:690-5 doi: http://dx.doi.org/10.1016/S0168-8278(00)80297-4

12. Hromadnikova I, Zlacka D, Hien Nguyen TT, Sedlackova L, Zejskova L, Sosna A. Fetal cells of mesenchymal origin in cultures derived from synovial tissue and skin of patients with rheumatoid arthritis. Joint Bone Spine. 2008;75:563-6 doi: http://dx.doi.org/10.1016/j.jbspin.2008.02.004

13. Lo YM, Lau TK, Chan LY, Leung TN, Chang AM. Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem. 2000; 46:1301-9

14. Burlingham WJ. A lesson in tolerance--maternal instruction to fetal cells. N Engl J Med. 2009;360:1355- 7 doi: http://dx.doi.org/10.1056/NEJMcibr0810752

15. Klintschar M, Schwaiger P, Mannweiler S, Regauer S, Kleiber M. Evidence of fetal microchimerism in Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 2001;86:2494-8 doi: http://dx.doi.org/10.1210/jc.86.6.2494

16. 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;358:2034-8

17. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA. 2004;292:75- 80 doi: http://dx.doi.org/10.1001/jama.292.1.75.

18. Bayes-Genis A, Bellosillo B, de la Calle O, Salido M, Roura S, Ristol FS, et al. Identification of male cardiomyocytes of extracardiac origin in the hearts of women with male progeny: male fetal cell microchimerism of the heart. J Heart Lung Transplant. 2005; 24:2179- 83 doi: http://dx.doi.org/10.1016/j.healun.2005.06.003

19. O’Donoghue K. Implications of fetal stem cell trafficking in pregnancy. Reviews in Gynaecological and Perinatal Practice. 2006;6:87-98 doi: http://dx.doi.org/10.1016/j.rigapp.2005.11.001.

20. Lepez T, Vandewoestyne M, Deforce D. Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland? Chimerism. 2013;4(4):111-8. doi: https://doi.org/10.4161/chim.25055

21. Ando T, Davies TF. Self-recognition and the role of fetal microchimerism. Best Pract Res Clin Endocrinol Metab. 2004;18:197-211 doi: http://dx.doi.org/10.1016/j.beem.2004.03.002

22. Lambert NC, Evans PC, Hashizumi TL, Maloney S, Gooley T, Furst DE, 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

23. Aractingi S, Uzan S, Dausset J, Carosella ED. Microchimerism in human diseases. Immunol Today. 2000;21:116-8 doi: http://dx.doi.org/10.1016/S0167-5699(99)01580-7

24. Fujiki Y, Johnson KL, Peter I, Tighiouart H, Bianchi DW. Fetal cells in the pregnant mouse are diverse and express a variety of progenitor and differentiated cell markers. Biol Reprod. 2009;81:26-32 doi: http://dx.doi.org/10.1095/biolreprod.108.074468

25. Khosrotehrani K, Bianchi DW. Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse. J Cell Sci. 2005;118:1559-63 doi: http://dx.doi.org/10.1242/jcs.02332

26. Leduc M, Aractingi S, Khosrotehrani K. Fetal-cell microchimerism, lymphopoiesis, and autoimmunity. Arch Immunol Ther Exp (Warsz). 2009;57:325-9 doi: http://dx.doi.org/10.1007/s00005-009-0044-7.

27. Cirello V, Rizzo R, Crippa M, Campi I, Bortolotti D, et al. Fetal cell microchimerism: a protective role in autoimmune thyroid diseases. Eur J Endocrinol. 2015;173(1):111-8. doi: https://doi.org/10.1530/EJE-15-0028

28. Adams KM, Nelson JL. Microchimerism: an investigative frontier in autoimmunity and transplantation. JAMA. 2004;291(9):1127-1131. doi: https://doi.org/10.1001/jama.291.9.1127

29. Ando T, Davies TF. Clinical Review 160: Postpartum autoimmune thyroid disease: the potential role of fetal microchimerism. J Clin Endocrinol Metab. 2003;88(7):2965-71. doi: https://doi.org/10.1210/jc.2002-021903

30. Klintschar M, Schwaiger P, Mannweiler S, Regauer S, Kleiber M. Evidence of fetal microchimerism in Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 2001;86:2494–2498

31. Ando T, Imaizumi M, Graves P, Unger P, Davies T. Fetal microchimerism in human Graves’ disease. J Clin Endocrinol Metab. 2002;87:3315–3320

32. 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;358:2034–2038

33. Lambert NC, Erickson TD, Yan Z, et al. Quantification of maternal microchimerism by hla-specific real-time polymerase chain reaction: Studies of healthy women and women with scleroderma. Arthritis & Rheumatism. 2004;50(3):906-914. doi: https://doi.org/10.1002/art.20200

34. Renne C, Ramos Lopez E, Steimle-Grauer SA, 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. The Journal of Clinical Endocrinology & Metabolism. 2004;89(11):5810-5814. doi: https://doi.org/10.1210/jc.2004-1049

35. Ludgate M, Lepez T, Vandewoestyne M, Hussain S, Van Nieuwerburgh F, Poppe K, et al. Fetal Microchimeric Cells in Blood of Women with an Autoimmune Thyroid Disease. PloS One. 2011;6(12):e29646. doi: https://doi.org/10.1371/journal.pone.0029646

36. Lepez T, Vandewoestyne M, Hussain S, Van Nieuwerburgh F, Poppe K, Velkeniers B, Kaufman JM, Deforce D. Fetal microchimeric cells in blood of women with an autoimmune thyroid disease. PLoS One. 2011;6(12):e29646. doi: https://doi.org/10.1371/journal.pone.0029646

37. Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol. 2010 6:311–318

38. Nelson JL. Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum. 1996;39:191–4. doi: https://doi.org/10.1002/art.1780390203

39. Klonisch T, Drouin R. Fetal-maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease. Trends Mol Med. 2009;15:510–8. doi: https://doi.org/10.1016/j.molmed.2009.09.002

40. Miech RP. The role of fetal microchimerism in autoimmune disease. Int J Clin Exp Med. 2010;3:164–8

41. Galofré JC. Microchimerism in graves’ disease. J Thyroid Res. 2012;2012:724382. doi: https://doi.org/10.1155/2012/724382

42. Klintschar M, Immel UD, Kehlen A, Schwaiger P, Mustafa T, et al. Fetal microchimerism in Hashimoto’s thyroiditis: a quantitative approach. Eur J Endocrinol. 2006;154:237–241

43. Kung AW, Jones BM. A change from stimulatory to blocking antibody activity in Graves’ disease during pregnancy. J Clin Endocrinol Metab. 1998;83(2):514-8. doi: https://doi.org/10.1210/jcem.83.2.4598

44. Amino N, Izumi Y, Hidaka Y, Takeoka K, Nakata Y, et al. No increase of blocking type anti-thyrotropin receptor antibodies during pregnancy in patients with Graves’ disease. J Clin Endocrinol Metab. 2003;88(12):5871-4. doi: https://doi.org/10.1210/jc.2003-030971

45. Mandel SJ, Spencer CA, Hollowell JG. Are detection and treatment of thyroid insufficiency in pregnancy feasible? Thyroid. 2005;15(1):44-53. doi: https://doi.org/10.1089/thy.2005.15.44

46. Lazarus JH. Epidemiology and prevention of thyroid disease in pregnancy. Thyroid. 2002;12(10):861-5. doi: https://doi.org/10.1089/105072502761016485. Erratum in: Thyroid. 2003 Apr;13(4):415

47. Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol. 2010;6:311-8 doi: http://dx.doi.org/10.1038/nrendo.2010.46

48. 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. doi: https://doi.org/10.1056/NEJM199804233381704

49. Nakagawa Y, Mori K, Hoshikawa S, Yamamoto M, Ito S, Yoshida K. Postpartum recurrence of Graves’ hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy. Clin Endocrinol (Oxf ). 2002;57(4):467-71. doi: https://doi.org/10.1046/j.1365-2265.2002.01615.x

50. Benhaim Rochester D, Davies TF. Increased risk of Graves’ disease after pregnancy. Thyroid. 2005;15(11):1287-90. doi: https://doi.org/10.1089/thy.2005.15.1287

51. Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol. 2003;48:641-59 doi: http://dx.doi.org/10.1067/mjd.2003.257

52. Prummel MF, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150:605-18 doi: http://dx.doi.org/10.1530/eje.0.1500605

53. Rust DW, Bianchi DW. Microchimerism in endocrine pathology. Endocr Pathol. 2009;20(1):11-6. doi: https://doi.org/10.1007/s12022-009-9064-4

54. Cirello V, Perrino M, Colombo C, Muzza M, Filopanti M, Vicentini L, et al. Fetal cell microchimerism in papillary thyroid cancer: studies in peripheral blood and tissues. Int J Cancer. 2010;126:2874–8

55. Saranac L, Zivanovic S, Bjelakovic B, Stamenkovic H, Novak M, Kamenov B. Why is the thyroid so prone to autoimmune disease? Horm Res Paediatr. 2011;75:157–65. doi: https://doi.org/10.1159/000324442

56. Tapia G, Mortimer G, Ye J, Gillard BT, Chipper-Keating S, Mårild K, et al. Maternal microchimerism in cord blood and risk of childhoodonset type 1 diabetes. Pediatr Diabetes. 2019;20(6):728-735. doi: https://doi.org/10.1111/pedi.12875

57. Vanzyl B, Planas R, Ye Y, Foulis A, de Krijger RR, Vives-Pi M, Gillespie KM. Why are levels of maternal microchimerism higher in type 1 diabetes pancreas? Chimerism. 2010;1:45–50

58. Allen LA, Taylor PN, Gillespie KM, Oram RA, Dayan CM. Maternal type 1 diabetes and relative protection against offspring transmission. Lancet Diabetes Endocrinol. 2023;11(10):755-767. doi: https://doi.org/10.1016/S2213-8587(23)00190-0

59. Ushijima K, Okuno M, Ayabe T, Kikuchi N, Kawamura T, et al; Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. Low prevalence of maternal microchimerism in peripheral blood of Japanese children with type 1 diabetes. Diabet Med. 2020;37(12):2131-2135. doi: https://doi.org/10.1111/dme.14221. Epub 2020 Jan 7. PMID: 31872455.

60. Vanzyl B, Planas R, Ye Y, Foulis A, de Krijger RR, Vives-Pi M, Gillespie KM. Why are levels of maternal microchimerism higher in type 1 diabetes pancreas? Chimerism. 2010;1(2):45-50. doi: https://doi.org/10.4161/chim.1.2.13891


Supplementary files

1. Figure 1. FISH and repeat FISH.
Subject
Type Исследовательские инструменты
View (459KB)    
Indexing metadata ▾
2. Figure 2. Potential mechanisms of deleterious (red), beneficial (green), and harmless (blue) microchimerism in the thyroid gland (adapted from [20] Lepez T. et al.).
Subject
Type Исследовательские инструменты
View (2MB)    
Indexing metadata ▾

Review

For citations:


Alaverdova M.V., Troshina E.A. The role of microchimerism in the development of endocrine diseases (using autoimmune thyroid diseases and type 1 diabetes mellitus as examples). Problems of Endocrinology. 2026;72(1):38-47. (In Russ.) https://doi.org/10.14341/probl13636

Views: 2323

JATS XML

ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)