Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet beta cell microchimerism.
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 beta cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and beta cell insulin staining. Female islet beta 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 beta cells in a mother's progeny.
Nelson
J Lee
JL
Human Immunogenetics, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA. nelsonlab@fhcrc.org
Gillespie
Kathleen M
KM
Lambert
Nathalie C
NC
Stevens
Anne M
AM
Loubiere
Laurence S
LS
Rutledge
Joe C
JC
Leisenring
Wendy M
WM
Erickson
Timothy D
TD
Yan
Zhen
Z
Mullarkey
Meghan E
ME
Boespflug
Nick D
ND
Bingley
Polly J
PJ
Gale
Edwin A M
EA
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D009035:Mothers; D016133:Polymerase Chain Reaction
D006680:HLA Antigens