Quantitative analysis of microchimerism in systemic sclerosis skin tissue

Ohtsuka, Tsutomu; Miyamoto, Yukari; Yamakage, Akio; Yamazaki, Soji

doi:10.1007/s004030100245

Cited by 59 publications

(27 citation statements)

References 14 publications

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“…Cases and controls from the selected studies were assessed for our inclusion/exclusion criteria. Eleven of 35 studies had subjects meeting the inclusion criteria (7,(11)(12)(13)(15)(16)(17)(18)(19)(20)(21). Individual data from 124 of 447 study subjects were extracted from these 11 studies and analyzed (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review

Khosrotehrani¹,

Johnson²,

Lau³

et al. 2003

Arthritis & Rheumatism

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Objective. Fetal cells enter the maternal circulation during most pregnancies. Their persistence for years occurs in only some women and has been associated with several autoimmune diseases such as systemic sclerosis. The objective of this study was to determine whether pregnancy history influences the persistence of fetal microchimeric cells.Methods. We reviewed all reports of studies on fetal cell microchimerism, defined as male DNA in maternal tissue, that describe individual pregnancy histories, disease diagnoses, and microchimerism status. The total numbers of pregnancies, births, and sons, the history of fetal loss (spontaneous abortion and elective termination), and the presence of a maternal autoimmune disease were tested as factors potentially associated with persistent microchimerism.Results. One hundred twenty-four subjects from 11 studies met the inclusion criteria. Only fetal loss was significantly associated with the presence of microchimerism (odds ratio 2.4, 95% confidence interval 1.2-6.0).Conclusion. These results suggest that fetomaternal cell trafficking following fetal loss may be important for the engraftment of microchimeric cells in maternal tissue. This may be due to an increased amount of fetomaternal transfusion or to transfer of a cell type that is more likely to engraft. We recommend that investigators in future studies on microchimerism report detailed pregnancy information, since these data are critical for the understanding of factors that influence the development of fetal cell microchimerism.

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Section: Resultsmentioning

confidence: 99%

“…In addition, in two of the studies (16,20), detailed pregnancy information was available only for subjects with autoimmune disease and detectable microchimerism. Therefore, in the current study, the observed association between microchimerism and autoimmune disease is biased.…”

Section: Discussionmentioning

confidence: 99%

The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review

Khosrotehrani¹,

Johnson²,

Lau³

et al. 2003

Arthritis & Rheumatism

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“…An important observation that arose from studies of fetal microchimerism in systemic sclerosis was that the simple presence of microchimerism is common in healthy individuals, and quantitative techniques are important in the comparison of patients to controls (10,11). Whereas male DNA can be quantified in women who gave birth to sons as a measure of fetal microchimerism, another approach was needed for MMc.…”

Section: Maternal Cells Have Recently Been Found In the Circulation Amentioning

confidence: 99%

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Nelson

Gillespie

Lambert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

168

167

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Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0 -530), 0 (0 -153), and 0 (0 -7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%). In other studies, we looked for female islet ␤ cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and ␤ cell insulin staining. Female islet ␤ cells (presumed maternal) formed 0.39 -0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet ␤ cells in a mother's progeny.quantitative PCR ͉ chimerism ͉ autoimmunity ͉ pancreas ͉ HLA

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“…This is in accordance with the fact that several studies have not found any association with the presence of FMc. In SSc skin tissue, 29% of women affected with SSc compared with 35% of healthy women presented fetal cells (Gannage et al 2002;Ohtsuka et al 2001). In primary biliary cirrhosis, authors did not find any significant differences when they compared affected and healthy women (Corpechot et al 2000;Fanning et al 2000;Tanaka et al 1999).…”

Section: Immune Reactions Triggered By Fetal Microchimeric Cellsmentioning

confidence: 79%

Fetal-cell microchimerism, lymphopoiesis, and autoimmunity

Leduc

Aractingi

Khosrotehrani

2009

Arch. Immunol. Ther. Exp.

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During all human and murine pregnancies, fetal cells enter the maternal circulation and tissues and may persist there for decades. The immune consequences of this phenomenon have been explored for many years as a potential origin of autoimmunity or protection from cancer in women after pregnancy. The leading hypothesis, suggesting that semi-allogenic fetal T cells may trigger a graft-versus-host type of disease, has been supported by several studies showing an increased frequency of fetal-cell microchimerism (FMc) in women affected with systemic sclerosis. However, a large proportion of healthy women or women affected with non-immune disorders also display fetal T cells, challenging the direct pathogenic role of such cells. In addition, recent evidence showing the transfer of various fetal progenitor cells to the mother during gestation has shed new light on the interpretation of microchimerism in autoimmunity. This review discusses the functional capacity of fetal hematopoietic progenitors to form T and B cells in maternal hematopoietic tissues, where they undergo an educational process probably resulting in tolerance to maternal antigens. Therefore, hypotheses other than the transfer of fetal cells to the mother's circulation should be considered in explaining the observed association of FMc and autoimmune disorders.

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Quantitative analysis of microchimerism in systemic sclerosis skin tissue

Cited by 59 publications

References 14 publications

The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review

The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Fetal-cell microchimerism, lymphopoiesis, and autoimmunity

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