Unusual transplant immunology case

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File this under something that we are never likely to see in clinical practice. In 2002 a fascinating case report was published in the New England Journal of Medicine concerning unusual findings during a work-up for a living related kidney transplant. A 52-year old woman had FSGS and was approaching ESRD. Her three sons were willing donors but when they went for HLA typing, there was a problem. Although all of her sons had a HLA haplotype from their father, two of the three had a HLA haplotype which, while identical to each other, did not match either of their mother’s HLA haplotypes suggesting that she could not be their mother! Further investigation revealed that her sons’ non-paternal HLA haplotype was identical to that of the patient’s brother and had ultimately been derived from her deceased father.

Further analysis of the patient’s blood found that there was no evidence of two distinct cell populations. However, hair follicles, buccal mucosa, bladder samples from a prior cystoscopy and thyroid cells from a prior resection found 4 haplotypes in these tissues. Only two were present in her peripheral blood. There was a normal number of chromosomes in all cells. This was a case of tetragametic chimerism. It is likely that there were two fertilized embryos in utero and that they fused at some point during development to form a single individual. It turns out that under experimental conditions inducing chimerism in mice, it is not unusual for such individuals to express a single haplotype pair in the peripheral blood while continuing to have all 4 haplotypes in other tissues. No-one really knows how common this condition is although the authors suggest that it may be more common than we appreciate. It has important implications in particular for forensic science.
One of the more interesting aspects of this case was that the patient had a HLA identical brother and a HLA haploidentical brother. Although she appropriately lysed cells from control individuals, she did not react to cells from her brother despite the fact that her lymphocytes carried a different HLA haplotype. She was fully tolerant to her brother.

A couple of years later, a woman in Washington State was in the middle of a paternity suit after separating from the father of her two children. She was pregnant with the third child at the time. Testing revealed that he was indeed the father of the children but that she was not. She was charged with fraud and accused of taking part in a surrogacy scam. Her children were taken off her and when her third child was born, this child was tested too and also found not to be her child. Her lawyer found this case report and asked for further testing – results of a smear test revealed that the DNA in that sample matched her children – she was a chimera also. Her children were promptly returned.

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