Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block

Stevens, Anne M.; Hermes, H.; Rutledge, Joe C.; Buyon, Jill P.; Nelson, J. Lee

doi:10.1016/s0140-6736(03)14795-2

Cited by 172 publications

(145 citation statements)

References 39 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…On the detrimental side, maternal cells could be effectors in ''autoimmunity'' as has been proposed in children with dermatomyositis (20). A second possibility is that differentiated, tissue-specific maternal cells could become targets of an ''autoimmune'' response as has been suggested in infants with neonatal lupus and congenital heart block (16). A third possibility is that MMc could function beneficially by providing an additional source for tissue repair as has been suggested for fetal microchimerism (21) or possibly diversity in response to infection.…”

Section: Discussionmentioning

confidence: 99%

“…Two other samples derived from infants: one infant had hypoplastic heart disease (8 weeks) and the other had cardiomyopathy (4 weeks), with the latter born to a mother with T1D. Female cells (presumed maternal) were identified by FISH for X and Y chromosomes in male pancreases and simultaneously studied for phenotype employing concomitant immunohistochemistry for insulin and CD45 on the same section (and same cells) (16).…”

Section: Prevalence and Levels According To Demographic And Clinicalmentioning

confidence: 99%

See 1 more Smart Citation

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.

170

166

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Prevalence and Levels According To Demographic And Clinicalmentioning

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.

170

166

View full text Add to dashboard Cite

show abstract

“…Female cells (presumed to be maternal) have been described in the tissues of male neonates (14), and an increase in the number of female cells has been reported in the muscle tissues of children with dermatomyositis (15) or idiopathic myositis (16). We recently identified maternal (female) cardiac myocytes in the heart muscle and atrioventricular node of male infants who died of heart block associated with neonatal lupus syndrome (17), suggesting the additional possibility that maternal cells could potentially be tissue targets of immune response (or, alternatively, could be involved in tissue repair). Whether maternal microchimerism is involved in SLE, contributing to blood or tissues, is unknown and will be an area of additional interest for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Maternal HLA class II compatibility in men with systemic lupus erythematosus

Stevens

Tsao

Hahn

et al. 2005

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Maternal-fetal cell transfer during pregnancy can lead to long-lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother-son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women.Methods. HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers.Results. Sons with SLE were HLA-identical with their mothers (bidirectionally compatible) for the basic HLA-DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P ‫؍‬ 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P ‫؍‬ 0.08). For DQA1 and DQB1, the ORs were 2.3 (P ‫؍‬ 0.08) and 2.0 (P ‫؍‬ 0.21), respectively. When analysis was limited to male subjects with SLEassociated HLA genes (encoding HLA-DR2 or HLA-DR3), the differences further increased for DRB1 basic groups (OR 7.2, P ‫؍‬ 0.01), DRB1 alleles (OR 15.0, P ‫؍‬ 0.018), DQA1 6.4 (P ‫؍‬ 0.006), and DQB1 (OR 5.7, P ‫؍‬ 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus.Conclusion. We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.

show abstract

“…63 In the pancreas from diabetic children, maternal Mc cells were insulin producing islet cells and not hematopoietic CD45 + . 64 This absence of hematopoietic cells is against the idea that maternal cells directly react against fetal/offspring tissues in the context of autoimmunity.…”

Section: Possible Roles Of Maternal Microchimeric Cells On the Contrimentioning

confidence: 96%

“…62 Additionally, using FISH, Stevens et al found maternal Mc cells in male neonates affected with neonatal lupus syndrome (NLS) and congenital heart block. 63 Finally, using non shared maternal-specific HLA PCR, Nelson et al reported that the occurrence of maternal Mc cells in the circulation was higher in young patients with T1D than among their healthy siblings or healthy controls. 53 Although these studies unanimously point to an association of maternal Mc with autoimmunity in children, they failed to show that maternal cells and more specifically, T cells, were the effectors triggering the disease when analysing the affected organs.…”

Section: Maternal Microchimerism May Trigger Allogeneic Responsesmentioning

confidence: 99%

Can maternal microchimeric cells influence the fetal response toward self antigens?

Lévêque

Khosrotehrani

2011

Chimerism

View full text Add to dashboard Cite

Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block

Cited by 172 publications

References 39 publications

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

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

Maternal HLA class II compatibility in men with systemic lupus erythematosus

Can maternal microchimeric cells influence the fetal response toward self antigens?

Contact Info

Product

Resources

About