Microchimerism Explained

Microchimerism is the presence of a small number of cells in an individual that have originated from another individual and are therefore genetically distinct. This phenomenon may be related to certain types of autoimmune diseases although the responsible mechanisms are unclear. The term comes from the prefix "micro" + "chimerism" based on the hybrid Chimera of Greek mythology. The concept was first discovered in the 1960s with the term gaining usage in the 1970s.[1]

Types

Human

In humans (and perhaps in all placental mammals), the most common form is fetomaternal microchimerism (also known as fetal cell microchimerism or fetal chimerism) whereby cells from a fetus pass through the placenta and establish cell lineages within the mother. Fetal cells have been documented to persist and multiply in the mother for several decades.[2] The exact phenotype of these cells is unknown, although several different cell types have been identified, such as various immune lineages, mesenchymal stem cells, and placental-derived cells.[3] A 2012 study at the Fred Hutchinson Cancer Research Center, Seattle, has detected cells with the Y chromosome in multiple areas of the brains of deceased women.[4]

Fetomaternal microchimerism occurs during pregnancy and shortly after giving birth for most women. However, not all women who have had children contain fetal cells. Studies suggest that fetomaternal microchimerism could be influenced by killer-cell immunoglobulin-like (KIR) ligands. Lymphocytes also influence the development of persisting fetomaternal microchimerism since natural killer cells compose about 70% of lymphocytes in the first trimester of pregnancy. KIR patterns on maternal natural killer cells of the mother and KIR ligands on the fetal cells could have an effect on fetomaternal microchimerism. In one study, mothers with KIR2DS1 exhibited higher levels of fetomaternal microchimerism compared to mothers who were negative for this activating KIR.[5]

The potential health consequences of these cells are unknown. One hypothesis is that these fetal cells might trigger a graft-versus-host reaction leading to autoimmune disease. This offers a potential explanation for why many autoimmune diseases are more prevalent in middle-aged women.[6] Another hypothesis is that fetal cells home to injured or diseased maternal tissue where they act as stem cells and participate in repair.[7] [8] It is also possible that the fetal cells are merely innocent bystanders and have no effect on maternal health.[9]

After giving birth, about 50–75% of women carry fetal immune cell lines. Maternal immune cells are also found in the offspring yielding in maternal→fetal microchimerism, though this phenomenon is about half as frequent as the former.[10]

Microchimerism had also been shown to exist after blood transfusions to a severely immunocompromised population of patients who suffered trauma.[11]

Other possible sources of microchimerism include gestation,[12] an individual's older sibling, twin sibling, or vanished twin, with the cells being received in utero. Fetal-maternal microchimerism is especially prevalent after abortion or miscarriage.[13]

Animal

Microchimerism occurs in most pairs of twins in cattle. In cattle (and other bovines), the placentas of fraternal twins usually fuse and the twins share blood circulation, resulting in exchange of cell lines. If the twins are a male–female pair, then XX/XY microchimerism results, and male hormones partially masculinize the heifer (female), creating a martin heifer or freemartin. Freemartins appear female, but are infertile and so cannot be used for breeding or dairy production. Microchimerism provides a method of diagnosing the condition, because male genetic material can be detected in a blood sample.[14]

Fetomaternal microchimerism in the brain

Several studies have identified male DNA in the brains of both humans and mice who have previously been pregnant with a male fetus.[15] [16] It has been suggested that the fetal-derived cells can differentiate into those capable of presenting neurotypical immunomarkers on their surface.[15] There has been no strong evidence to say microchimerism of the maternal brain leads to disease; however, Parkinson's disease correlates with a higher incidence of brain microchimeras.[15] Alzheimer's disease studies support nearly the opposite correlation: the more fetal-derived cells present, the lower the chance of the patient having had Alzheimer's.[16]

Maternal tolerance to paternal-fetal antigens

There are many mechanisms at the maternal-fetal interface to prevent immune rejection of fetal cells. Nevertheless, systemic immunological changes occur in pregnant women. For example, condition of women suffering from autoimmune disorders (e.g. rheumatoid arthritis, multiple sclerosis) improves during pregnancy.[17] [18] These changes in immune responses during pregnancy extend to maternal components specific to fetal antigens, because of feto-maternal cell transfer and their retention in mother tissues. During pregnancy, numbers of fetal cells in maternal tissues increase and correlate with expansion of CD4+ regulatory T cells (Tregs).[19] Decreased expansion and decidual accumulation of Treg cause pregnancy complications (preeclampsia, abortions).[19] In mice models, most mother's fetal-specific CD8+ T cells undergo clonal deletion[20] and express low levels of chemokine receptors and ligands – this prevents remaining fetal-specific CD8+ T cells from entering the maternal-fetal interface.[21] [22] Mother's fetal-specific CD4+ T cells proliferate, and due to FOXP3 expression, differentiate into Treg cells.[23] Mice models show that fetal-specific Treg cells are necessary for successful pregnancy.[24]

Fetal tolerance to noninherited maternal antigens

Fetal T cells accumulate during in utero development. Even though the fetus is exposed to noninherited maternal antigens (NIMAs), fetal CD4+ T cells are capable of alloantigen-induced proliferation, preferentially differentiating to Treg cells and preventing a fetal immune response to maternal antigens.[25] This expanded immune tolerance persists in both mother and offspring after birth and allows microchimeric cells to be retained in tissues.

Postnatal tolerance to NIMAs

NIMA-specific tolerance causes some interesting immunological phenotypes: sensitization to erythrocyte Rhesus factor (Rh) antigens is reduced among Rh- women born to Rh+ women,[26] long-term kidney allograft survival is improved in NIMA-matched donor-recipient sibling pairs,[27] or acuteness of bone marrow transplantation graft-versus-host disease is reduced, when recipients of donor stem cells are NIMA-matched.[28] Cross-fostering animal studies show that when postnatal NIMA exposure though breastfeeding is eliminated, survival of NIMA-matched allografts is reduced. This suggests that to maintain NIMA-specific tolerance in offspring, breastfeeding is essential, but ingestion of mother's cells alone does not prime NIMA-specific tolerance. Both prenatal and postnatal exposure to mother's cells is required to maintain NIMA-specific tolerance.[29]

Benefits of microchimeric cells

The severity of preexisting autoimmune disorders is reduced during pregnancy and it is most apparent when fetal microchimeric cells levels are highest - during the last trimester.[30] [18] These cells can also replace injured maternal cells and recover tissue function (type I diabetes mouse model showed replacement of defective maternal islet cells by fetal-derived pancreatic cells[31]). Fetal microchimeric cells can differentiate into cell types that infiltrate and replace injured cells in models of Parkinson's disease or myocardial infarction. They also help in wound healing by neoangiogenesis. Seeding of fetal microchimeric cells into maternal tissues has been proposed to promote care of offspring after birth (seeding of maternal breast tissue may promote lactation, and seeding of brain may enhance maternal attention).[29]

Relationship with autoimmune diseases and breast cancer

Microchimerism has been implicated in autoimmune diseases. Independent studies repeatedly suggested that microchimeric cells of fetal origin may be involved in the pathogenesis of systemic sclerosis.[2] [32] Moreover, microchimeric cells of maternal origin may be involved in the pathogenesis of a group of autoimmune diseases found in children, i.e. juvenile idiopathic inflammatory myopathies (one example would be juvenile dermatomyositis).[33] Microchimerism has now been further implicated in other autoimmune diseases, including systemic lupus erythematosus.[34] Contrarily, an alternative hypothesis on the role of microchimeric cells in lesions is that they may be facilitating tissue repair of the damaged organ.[35]

Moreover, fetal immune cells have also been frequently found in breast cancer stroma as compared to samples taken from healthy women. It is not clear, however, whether fetal cell lines promote the development of tumors or, contrarily, protect women from developing breast carcinoma.[36] [37]

Systemic lupus erythematosus

The presence of fetal cells in mothers can be associated with benefits when it comes to certain autoimmune diseases. In particular, male fetal cells are related to helping mothers with systemic lupus erythematosus. When kidney biopsies were taken from patients with lupus nephritis, DNA was extracted and run with PCR. The male fetal DNA was quantified and the presence of specific Y chromosome sequences were found. Women with lupus nephritis containing male fetal cells in their kidney biopsies exhibited better renal system functioning. Levels of serum creatinine, which is related to kidney failure, were low in mothers with high levels of male fetal cells. In contrast, women without male fetal cells who had lupus nephritis showed a more serious form of glomerulonephritis and higher levels of serum creatinine.[38]

The specific role that fetal cells play in microchimerism related to certain autoimmune diseases is not fully understood. However, one hypothesis states that these cells supply antigens, causing inflammation and triggering the release of different foreign antigens. This would trigger autoimmune disease instead of serving as a therapeutic. A different hypothesis states that fetal microchimeric cells are involved in repairing tissues. When tissues get inflamed, fetal microchimeric cells go to the damaged site and aid in repair and regeneration of the tissue.

Thyroid disease

Fetal maternal microchimerism may be related to autoimmune thyroid diseases. There have been reports of fetal cells in the lining of the blood and thyroid glands of patients with autoimmune thyroid disease. These cells could become activated after delivery of the baby after immune suppression in the mother is lost, suggesting a role of fetal cells in the pathogenesis of such diseases. Two types of thyroid disease, Hashimoto's thyroiditis (HT) and Graves' disease (GD), show similarities to graft vs host disease which occurs after hematopoietic stem cell transplants. Fetal cells colonize maternal tissues like the thyroid gland and are able to survive many years postpartum. These fetal microchimeric cells in the thyroid show up in the blood of women affected by thyroid diseases.[39]

Sjögren syndrome

Sjögren syndrome (SS) is an autoimmune rheumatic disease of the exocrine glands. Increased incidence of SS after childbirth suggests a relationship between SS and pregnancy, and this led to the hypothesis that fetal microchimerism may be involved in SS pathogenesis. Studies showed the presence of Y-chromosome-positive fetal cells in minor salivary glands in 11 of 20 women with SS but in only one of eight normal controls. Fetal cells in salivary glands suggest that they may be involved in the development of SS.[40]

Oral lichen planus

Lichen planus (LP) is a T-cell-mediated autoimmune chronic disease of unknown etiology. Females have a three times higher prevalence than men. LP is characterized by T lymphocytes infiltration of the lower levels of epithelium, where they damage basal cells and cause apoptosis. The fetal microchimerism may trigger a fetus versus host reaction and therefore may play a role in the pathogenesis of autoimmune diseases including LP.[41]

Breast cancer

Pregnancy has a positive effect on the prognosis of breast cancer according to several studies [42] [43] [44] and it apparently increases the chance of survival after diagnosis of breast cancer.[45] Possible positive effects of pregnancy could be explained by the persistence of fetal cells in the blood and maternal tissues.[46]

Fetal cells are probably actively migrating from peripheral blood into the tumor tissue [47] where they are preferentially settled in the tumor stroma[37] and one their concentration decreases as they get closer to the healthy breast tissue.[48] There are two suggested mechanisms by which the fetal cells could have the positive effect on the breast cancer prognosis. The first mechanism suggests that fetal cells only oversee cancer cells and they attract components of the immune system if needed. The second option is that the down-regulation of the immune system induced by the presence of fetal cells could ultimately lead to cancer prevention, because women in whom FMC is present produce lower concentrations of inflammatory mediators, which may lead to the development of neoplastic tissue.[49]

The effect also depends on the level of microchimerism: Hyperchimerism (a high rate of microchimerism) and hypochimerism (a low rate of microchimerism) can be related to the negative effect of FMC and thus can promote a worse prognosis of breast cancer.[50] [51] Apparently, women with breast cancer may fail in the process of obtaining and maintaining allogeneic fetal cells. Low concentration and / or complete absence of fetal cells could indicate a predisposition to development of the malignant process.

Other cancers

Study of S. Hallum shows association between male origin fetal cells and ovarian cancer risk. Presence of Y chromosome was used to detect foreign cells in women's blood. Microchimerism is a result of pregnancy, possibility that foreign cells were of transfusion or transplantation origin was rejected due to women's health. Women testing positive for male origin microchimerism cells had reduced hazard rates of ovarian cancer than women testing negative.[52] Pregnancy at older ages can reduce risk of ovarian cancer. Numbers of microchimeric cells declines after pregnancy, and ovarian cancer is most frequent in postmenopausal women. This suggests that fetal microchimerism may play a protective role in ovarian cancer as well.Microchimeric cells also cluster several times more in lung tumors than in surrounding healthy lung tissue. Fetal cells from the bone marrow go to the tumor sites where they may have tissue repair functions.[53] Microchimerism of fetomaternal cell trafficking origin might be associated with the pathogenesis or progression of cervical cancer. Male cells were observed in patients with cervical cancer but not in positive controls. Microchimeric cells might induce the alteration of the woman's immune system and make the cervical tissue more susceptible to HPV infection or provide a suitable environment for tumor growth.[54]

Role of microchimerism in wound healing

Microchimeric fetal cells expressed collagen I, III and TGF-β3, and they were identified in healed maternal cesarean section scars. This suggests that these cells migrate to the site of damage due to maternal skin injury signals, and help repair tissue.[55]

Stem cells

Animal models

Fetomaternal microchimerism has been shown in experimental investigations of whether fetal cells can cross the blood brain barrier in mice. The properties of these cells allow them to cross the blood brain barrier and target injured brain tissue. This mechanism is possible because umbilical cord blood cells express some proteins similar to neurons. When these umbilical cord blood cells are injected in rats with brain injury or stroke, they enter the brain and express certain nerve cell markers. Due to this process, fetal cells could enter the brain during pregnancy and become differentiated into neural cells. Fetal microchimerism can occur in the maternal mouse brain, responding to certain cues in the maternal body.[56]

Health implications

Fetal microchimerism could have an implication on maternal health. Isolating cells in cultures can alter the properties of the stem cells, but in pregnancy the effects of fetal stem cells can be investigated without in vitro cultures. Once characterized and isolated, fetal cells that are able to cross the blood brain barrier could impact certain procedures. For example, isolating stem cells can be accomplished through taking them from sources like the umbilical cord. These fetal stem cells can be used in intravenous infusion to repair the brain tissue. Hormonal changes in pregnancy alter neurogenesis, which could create favorable environments for fetal cells to respond to injury.

The true function on fetal cells in mothers is not fully known, however, there have been reports of positive and negative health effects. The sharing of genes between the fetus and mother may lead to benefits. Due to not all genes being shared, health complications may arise as a result of resource allocation. During pregnancy, fetal cells are able to manipulate the maternal system to draw resources from the placenta, while the maternal system tries to limit it.[57]

See also

Further reading

Notes and References

  1. Naik . Rupali . Shrivastava . Sandhya . Suryawanshi . Hema . Gupta . Neha . Microchimerism: A new concept . Journal of Oral and Maxillofacial Pathology . Medknow . 23 . 2 . 2019 . 0973-029X . 10.4103/jomfp.jomfp_85_17 . 311. 31516258 . 6714269 . free .
  2. Evans . Paul C. . Lambert . Nathalie . Maloney . Sean . Furst . Dan E. . Moore . James M. . Nelson . J. Lee . Long-Term Fetal Microchimerism in Peripheral Blood Mononuclear Cell Subsets in Healthy Women and Women With Scleroderma . Blood . 15 March 1999 . 93 . 6 . 2033–2037 . 10.1182/blood.V93.6.2033.406k18_2033_2037 . 10068676 .
  3. Pritchard S, Wick HC, Slonim DK, Johnson KL, Bianchi DW . Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung . Biology of Reproduction . 87 . 2 . 42 . August 2012 . 22674387 . 3431427 . 10.1095/biolreprod.112.101147 .
  4. Chan WF, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL . Male microchimerism in the human female brain . PLOS ONE . 7 . 9 . e45592 . 26 September 2012 . 23049819 . 3458919 . 10.1371/journal.pone.0045592 . 2012PLoSO...745592C . free .
  5. Kruchen . Anne . Stahl . Tanja . Gieseke . Friederike . Binder . Thomas MC . Oezcan . Zakir . Meisel . Roland . Kreyenberg . Hermann . Bader . Peter . Gruhn . Bernd . Greil . Johann . Pfeiffer . Matthias . Doering . Michaela . Handgretinger . Rupert . Fehse . Boris . Mueller . Ingo . Fetomaternal Microchimerism Is Associated with Better Outcome in Haploidentical Hematopoietic Stem Cell Transplantation . Blood . 6 December 2014 . 124 . 21 . 1242 . 10.1182/blood.V124.21.1242.1242 .
  6. Nelson JL . Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? . Arthritis and Rheumatism . 39 . 2 . 191–4 . February 1996 . 8849367 . 10.1002/art.1780390203 . free .
  7. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW . Transfer of fetal cells with multilineage potential to maternal tissue . JAMA . 292 . 1 . 75–80 . July 2004 . 15238593 . 10.1001/jama.292.1.75 . free .
  8. Nguyen Huu S, Oster M, Avril MF, Boitier F, Mortier L, Richard MA, Kerob D, Maubec E, Souteyrand P, Moguelet P, Khosrotehrani K, Aractingi S . Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy . The American Journal of Pathology . 174 . 2 . 630–7 . February 2009 . 19147820 . 2630570 . 10.2353/ajpath.2009.080566 .
  9. Johnson KL, Bianchi DW . Fetal cells in maternal tissue following pregnancy: what are the consequences? . Human Reproduction Update . 10 . 6 . 497–502 . 2004 . 15319378 . 10.1093/humupd/dmh040 . free .
  10. Loubière LS, Lambert NC, Flinn LJ, Erickson TD, Yan Z, Guthrie KA, Vickers KT, Nelson JL . Maternal microchimerism in healthy adults in lymphocytes, monocyte/macrophages and NK cells . Laboratory Investigation; A Journal of Technical Methods and Pathology . 86 . 11 . 1185–92 . November 2006 . 16969370 . 10.1038/labinvest.3700471 . free .
  11. Reed W, Lee TH, Norris PJ, Utter GH, Busch MP . Transfusion-associated microchimerism: a new complication of blood transfusions in severely injured patients . Seminars in Hematology . 44 . 1 . 24–31 . January 2007 . 17198844 . 10.1053/j.seminhematol.2006.09.012 .
  12. Shree . R . Harrington . We . Kanaan . Sb . Forsyth . A . Cousin . E . Lopez . A . Nelson . Jl . Gammill . Hs . Fetal microchimerism by mode of delivery: a prospective cohort study . BJOG . January 2019 . 126 . 1 . 24–31 . 10.1111/1471-0528.15432 . 30102819 . 6294652 .
  13. Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW . The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review . Arthritis and Rheumatism . 48 . 11 . 3237–41 . November 2003 . 14613289 . 10.1002/art.11324 .
  14. Fujishiro . A. . Kawakura . K. . Miyake . Y-I. . Kaneda . Y. . A fast, convenient diagnosis of the bovine freemartin syndrome using polymerase chain reaction . Theriogenology . 1 April 1995 . 43 . 5 . 883–891 . 10.1016/0093-691X(95)00039-B . 16727678 .
  15. Zeng . Xiao Xia . Tan . Kian Hwa . Yeo . Ailing . Sasajala . Piriya . Tan . Xiaowei . Xiao . Zhi Cheng . Dawe . Gavin . Udolph . Gerald . Pregnancy-Associated Progenitor Cells Differentiate and Mature into Neurons in the Maternal Brain . Stem Cells and Development . December 2010 . 19 . 12 . 1819–1830 . 10.1089/scd.2010.0046 . 20707697 .
  16. Chan . William F. N. . Gurnot . Cécile . Montine . Thomas J. . Sonnen . Joshua A. . Guthrie . Katherine A. . Nelson . J. Lee . Male Microchimerism in the Human Female Brain . PLOS ONE . 26 September 2012 . 7 . 9 . e45592 . 10.1371/journal.pone.0045592 . 23049819 . 3458919 . 2012PLoSO...745592C . 8057434 . free .
  17. Confavreux . C . Hutchinson . M . Hours . MM . Cortinovis-Tourniaire . P . Moreau . T . Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. . The New England Journal of Medicine . 30 July 1998 . 339 . 5 . 285–91 . 10.1056/NEJM199807303390501 . 9682040 . free .
  18. Østensen . Monika . Villiger . Peter M. . The remission of rheumatoid arthritis during pregnancy . Seminars in Immunopathology . 24 May 2007 . 29 . 2 . 185–191 . 10.1007/s00281-007-0072-5 . 17621703 . 5766992 .
  19. Jiang . Tony T. . Chaturvedi . Vandana . Ertelt . James M. . Kinder . Jeremy M. . Clark . Dayna R. . Valent . Amy M. . Xin . Lijun . Way . Sing Sing . Regulatory T Cells: New Keys for Further Unlocking the Enigma of Fetal Tolerance and Pregnancy Complications . The Journal of Immunology . 1 June 2014 . 192 . 11 . 4949–4956 . 10.4049/jimmunol.1400498 . 24837152 . 4030688 .
  20. Erlebacher . A . Vencato . D . Price . KA . Zhang . D . Glimcher . LH . Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus. . The Journal of Clinical Investigation . May 2007 . 117 . 5 . 1399–411 . 10.1172/JCI28214 . 17446933 . 1849983 .
  21. Chaturvedi . Vandana . Ertelt . James M. . Jiang . Tony T. . Kinder . Jeremy M. . Xin . Lijun . Owens . Kathryn J. . Jones . Helen N. . Way . Sing Sing . CXCR3 blockade protects against Listeria monocytogenes infection–induced fetal wastage . Journal of Clinical Investigation . 1 April 2015 . 125 . 4 . 1713–1725 . 10.1172/JCI78578 . 25751061 . 4396484 .
  22. Nancy . P. . Tagliani . E. . Tay . C.-S. . Asp . P. . Levy . D. E. . Erlebacher . A. . Chemokine Gene Silencing in Decidual Stromal Cells Limits T Cell Access to the Maternal-Fetal Interface . Science . 8 June 2012 . 336 . 6086 . 1317–1321 . 10.1126/science.1220030 . 22679098 . 3727649 . 2012Sci...336.1317N .
  23. Rowe . Jared H. . Ertelt . James M. . Xin . Lijun . Way . Sing Sing . Pregnancy imprints regulatory memory that sustains anergy to fetal antigen . Nature . October 2012 . 490 . 7418 . 102–106 . 10.1038/nature11462 . 23023128 . 3465465 . 2012Natur.490..102R .
  24. Xin . Lijun . Ertelt . James M. . Rowe . Jared H. . Jiang . Tony T. . Kinder . Jeremy M. . Chaturvedi . Vandana . Elahi . Shokrollah . Way . Sing Sing . Cutting Edge: Committed Th1 CD4 + T Cell Differentiation Blocks Pregnancy-Induced Foxp3 Expression with Antigen-Specific Fetal Loss . The Journal of Immunology . 1 April 2014 . 192 . 7 . 2970–2974 . 10.4049/jimmunol.1302678 . 24591368 . 3972488 .
  25. Mold . Jeff E. . Michaëlsson . Jakob . Burt . Trevor D. . Muench . Marcus O. . Beckerman . Karen P. . Busch . Michael P. . Lee . Tzong-Hae . Nixon . Douglas F. . McCune . Joseph M. . Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero . Science . 5 December 2008 . 322 . 5907 . 1562–1565 . 10.1126/science.1164511 . 19056990 . 2648820 . 2008Sci...322.1562M .
  26. Owen . Ray D. . Wood . Harold R. . Foord . Alvin G. . Sturgeon . Phillip . Baldwin . L. G. . Evidence for actively acquired tolerance to Rh antigens . Proceedings of the National Academy of Sciences of the United States of America . June 1954 . 40 . 6 . 420–424 . 10.1073/pnas.40.6.420 . 16589498 . 534062 . 1954PNAS...40..420O . free .
  27. Burlingham . William J. . Grailer . Alan P. . Heisey . Dennis M. . Claas . Frans H.J. . Norman . Douglas . Mohanakumar . Thalachallour . Brennan . Daniel C. . de Fijter . Hans . van Gelder . Teun . Pirsch . John D. . Sollinger . Hans W. . Bean . Michael A. . The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors . New England Journal of Medicine . 3 December 1998 . 339 . 23 . 1657–1664 . 10.1056/NEJM199812033392302 . 9834302 . free .
  28. van Rood . J. J. . Loberiza . FR . Zhang . MJ . Oudshoorn . M . Claas . F . Cairo . MS . Champlin . RE . Gale . RP . Ringdén . O . Hows . JM . Horowitz . MH . Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling . Blood . 1 March 2002 . 99 . 5 . 1572–1577 . 10.1182/blood.v99.5.1572 . 11861270 . free .
  29. Kinder . Jeremy M. . Stelzer . Ina A. . Arck . Petra C. . Way . Sing Sing . Immunological implications of pregnancy-induced microchimerism . Nature Reviews. Immunology . 2017 . 17 . 8 . 483–494 . 10.1038/nri.2017.38 . 28480895 . 5532073 .
  30. Confavreux . Christian . Hutchinson . Michael . Hours . Martine Marie . Cortinovis-Tourniaire . Patricia . Moreau . Thibault . Rate of Pregnancy-Related Relapse in Multiple Sclerosis . New England Journal of Medicine . 30 July 1998 . 339 . 5 . 285–291 . 10.1056/NEJM199807303390501 . 9682040 . free .
  31. Sunami . Rei . Komuro . Mayuko . Yuminamochi . Tsutomu . Hoshi . Kazuhiko . Hirata . Shuji . Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation . Journal of Reproductive Immunology . March 2010 . 84 . 2 . 117–123 . 10.1016/j.jri.2009.11.006 . 20116109 .
  32. Artlett . Carol M. . Smith . J. Bruce . Jimenez . Sergio A. . Identification of Fetal DNA and Cells in Skin Lesions from Women with Systemic Sclerosis . New England Journal of Medicine . 23 April 1998 . 338 . 17 . 1186–1191 . 10.1056/NEJM199804233381704 . 9554859 . free .
  33. Artlett CM, Ramos R, Jiminez SA, Patterson K, Miller FW, Rider LG . Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group . Lancet . 356 . 9248 . 2155–6 . 2000 . 11191545 . 10.1016/S0140-6736(00)03499-1 . 46327174 .
  34. Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW . Microchimerism in a female patient with systemic lupus erythematosus . Arthritis and Rheumatism . 44 . 9 . 2107–11 . September 2001 . 11592373 . 10.1002/1529-0131(200109)44:9<2107::AID-ART361>3.0.CO;2-9 . free .
  35. Gilliam AC . Microchimerism and skin disease: true-true unrelated? . The Journal of Investigative Dermatology . 126 . 2 . 239–41 . February 2006 . 16418731 . 10.1038/sj.jid.5700061 . free .
  36. Gadi VK, Nelson JL . Fetal microchimerism in women with breast cancer . Cancer Research . 67 . 19 . 9035–8 . October 2007 . 17909006 . 10.1158/0008-5472.CAN-06-4209 . free .
  37. Dubernard . Gil . Aractingi . Sélim . Oster . Michel . Rouzier . Roman . Mathieu . Marie-Christine . Uzan . Serge . Khosrotehrani . Kiarash . Breast cancer stroma frequently recruits fetal derived cells during pregnancy . Breast Cancer Research . February 2008 . 10 . 1 . R14 . 10.1186/bcr1860 . 18271969 . 2374970 . free .
  38. Florim GM, Caldas HC, de Melo JC, Baptista MA, Fernandes IM, Savoldi-Barbosa M, Goldman GH, Abbud-Filho M . Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect . Arthritis Research & Therapy . 17 . 101 . April 2015 . 1 . 25889410 . 4416327 . 10.1186/s13075-015-0615-4 . 2024-02-19 . free .
  39. Lepez T, Vandewoestyne M, Deforce D . Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland? . Chimerism . 4 . 4 . 111–8 . 20 May 2013 . 23723083 . 3921191 . 10.4161/chim.25055 .
  40. Endo . Y. . Negishi . I . Ishikawa . O . Possible contribution of microchimerism to the pathogenesis of Sjogren's syndrome . Rheumatology . 1 May 2002 . 41 . 5 . 490–495 . 10.1093/rheumatology/41.5.490 . 12011370 . free .
  41. Shrivastava . Sandhya . Naik . Rupali . Suryawanshi . Hema . Gupta . Neha . Microchimerism: A new concept . Journal of Oral and Maxillofacial Pathology . 2019 . 23 . 2 . 311 . 10.4103/jomfp.JOMFP_85_17 . 31516258 . 6714269 . free .
  42. Rosenberg L, Thalib L, Adami HO, Hall P . Childbirth and breast cancer prognosis . International Journal of Cancer . 111 . 5 . 772–6 . September 2004 . 15252849 . 10.1002/ijc.20323 . 8782090 . free .
  43. Olson . Sara H. . Zauber . Ann G. . Tang . Jian . Harlap . Susan . Relation of Time since Last Birth and Parity to Survival of Young Women with Breast Cancer . Epidemiology . November 1998 . 9 . 6 . 669–671 . 10.1097/00001648-199811000-00019 . 9799180 . free .
  44. Anderson . Penny R. . Hanlon . Alexandra L. . Freedman . Gary M. . Nicolaou . Nicos . Parity Confers Better Prognosis in Older Women with Early-Stage Breast Cancer Treated with Breast-Conserving Therapy . Clinical Breast Cancer . August 2004 . 5 . 3 . 225–231 . 10.3816/cbc.2004.n.026 . 15335456 .
  45. Warren Andersen S, Newcomb PA, Hampton JM, Titus-Ernstoff L, Egan KM, Trentham-Dietz A . Reproductive factors and histologic subtype in relation to mortality after a breast cancer diagnosis . Breast Cancer Research and Treatment . 130 . 3 . 975–80 . December 2011 . 21769659 . 4306414 . 10.1007/s10549-011-1666-0 .
  46. 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. . Proceedings of the National Academy of Sciences . 23 January 1996 . 93 . 2 . 705–708 . 10.1073/pnas.93.2.705 . 8570620 . 40117 . 1996PNAS...93..705B . free .
  47. Dubernard G, Oster M, Chareyre F, Antoine M, Rouzier R, Uzan S, Aractingi S, Khosrotehrani K . Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy . International Journal of Cancer . 124 . 5 . 1054–9 . March 2009 . 19065666 . 10.1002/ijc.24036 . 29640302 . free .
  48. Nemescu D, Ursu RG, Nemescu ER, Negura L . Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment . PLOS ONE . 11 . 1 . e0147675 . 2016-01-25 . 26808509 . 4726590 . 10.1371/journal.pone.0147675 . 2016PLoSO..1147675N . free .
  49. Coussens LM, Werb Z . Inflammation and cancer . Nature . 420 . 6917 . 860–7 . 2002-12-19 . 12490959 . 2803035 . 10.1038/nature01322 . 2002Natur.420..860C .
  50. Gadi VK, Malone KE, Guthrie KA, Porter PL, Nelson JL . Case-control study of fetal microchimerism and breast cancer . PLOS ONE . 3 . 3 . e1706 . March 2008 . 18320027 . 2248618 . 10.1371/journal.pone.0001706 . 2008PLoSO...3.1706G . free .
  51. Dhimolea E, Denes V, Lakk M, Al-Bazzaz S, Aziz-Zaman S, Pilichowska M, Geck P . High male chimerism in the female breast shows quantitative links with cancer . International Journal of Cancer . 133 . 4 . 835–42 . August 2013 . 23390035 . 10.1002/ijc.28077 . 23272121 . free .
  52. Hallum . Sara . Jakobsen . Marianne Antonius . Gerds . Thomas Alexander . Pinborg . Anja . Tjønneland . Anne . Kamper-Jørgensen . Mads . Male origin microchimerism and ovarian cancer . International Journal of Epidemiology . 2020 . 50 . 1 . 87–94 . 10.1093/ije/dyaa019. 0300-5771 . 32065627 . free .
  53. Sawicki . J. A. . Fetal Microchimerism and Cancer . Cancer Research . 1 December 2008 . 68 . 23 . 9567–9569 . 10.1158/0008-5472.CAN-08-3008 . 19047129 . 2638004 .
  54. Cha . D . Cervical cancer and microchimerism . Obstetrics & Gynecology . October 2003 . 102 . 4 . 774–781 . 10.1016/S0029-7844(03)00615-X . 14551008 .
  55. Mahmood . Uzma . O’Donoghue . Keelin . Microchimeric fetal cells play a role in maternal wound healing after pregnancy . Chimerism . April 2014 . 5 . 2 . 40–52 . 10.4161/chim.28746 . 24717775 . 4199806 .
  56. Tan XW, Liao H, Sun L, Okabe M, Xiao ZC, Dawe GS . Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier? . Stem Cells . 23 . 10 . 1443–52 . 1 November 2005 . 16091558 . 10.1634/stemcells.2004-0169 . 37875663 . free .
  57. Boddy AM, Fortunato A, Wilson Sayres M, Aktipis A . Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb . BioEssays . 37 . 10 . 1106–18 . October 2015 . 26316378 . 4712643 . 10.1002/bies.201500059 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Microchimerism".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.