To the Editor: I want to thank Drs. Zachary and Leffell for their interest in my manuscript, ‘Good Ethics Requires Good Science: Why Transplant Programs Should NOT Disclose Misattributed Parentage’ (1). Zachary and Leffell argue that genetic tests are very useful to evaluate parentage (2). I agree. They argue that HLA is very accurate (although ≤97%) for determining parentage (2); and again I agree. However, they misunderstand the main thesis of my manuscript which is that one should not assume, without extensive additional work-up, that inconsistencies in HLA and ABO between parent-child dyads for transplantation is misattributed paternity or misattributed maternity. My manuscript was in response to several case studies of presumed misattributed paternity (3-5) and a larger study by Young et al. that found 2.8% misattributed paternity and 1.9% misattributed maternity in the United Network for Organ Sharing (UNOS) database as determined by cases with less than a one haplotype (3/6) HLA match between parent and child (6). Their solution was to assume that the 1.9% misattributed maternity cases were data error and therefore claimed 0.9% misattributed paternity. In response, I argued three points. First, to make a claim of misattributed parentage is a very serious allegation and that HLA and ABO typing alone can provide a high degree of accuracy (7), but <97% accuracy is not high enough given the seriousness of the claim. In addition, HLA and ABO as markers for parentage are less accurate when only one parent's blood sample is available as in the case of UNOS database. The forensic literature is clear that HLA and ABO are much more accurate when you have triads versus dyads, and that accuracy is improved when at least 3 different chromosomes are evaluated (7-9). Second, there are genetic explanations for HLA mismatch that may not be determined even when triadic samples are available. There are several cases in the literature that reveal rare genetic explanations, from chimerism to uniparental disomy (10, 11). However, despite Zachary and Leffell's claim, we do not know how rare these events truly are (11). If the aim is to report misattributed parentage, alternative explanations should be disproven. And third, and most importantly, it is not the goal of transplantation programs to prove or disprove parentage. When an individual has end-stage renal disease, his or her parents or children provide samples for HLA and ABO testing to determine whether they are compatible donors. That is a yes/no question; although with newer methods of ABO-incompatible transplantation, it may not be so black-and-white as it was historically (12, 13). To suggest that transplant centers should inform parent-child dyads that a less than 3/6 antigen HLA match is evidence of misattributed paternity is morally, socially and scientifically irresponsible unless further evaluation is performed. And my point is that this further evaluation is not and should not be the responsibility of a transplant programs (1). If a dyad were to ask whether their HLA antigen mismatch signified non-genetic parentage, they should be told that it may represent non-parentage but that other explanations also exist. If they are interested, they should be referred to a genetic counselor who can do a more complete assessment. Thus, I disagree with Drs. Zachary and Leffell that ‘if parentage is in doubt, the protocol for verifying and handling that information should be determined by each transplant program and should consider the consequences of disclosure and non-disclosure’ (2). Rather, I reiterate what I wrote in the article: ‘I believe that the best practice for transplant programs when parent-child dyads have ABO or HLA inconsistencies that do not preclude donation would be to not provide explanations but only to provide the parties with their genetic information as objective facts’ (1). I also recommended that potential donor-recipient dyads who questioned their genetic relationships should be advised to seek consultation with a genetic professional who can do a more complete work-up and who has the skills to provide appropriate pre- and posttesting counseling (1). Funding: National Library of Medicine which is part of the National Instiitutes of Health (NIH). Conflicts of Interest: None. Dr. Ross currently serves on the Ethics Committee of the United Network for Organ Sharing/Organ Procurement and Transplant Network (UNOS/OPTN). The views reflected are her own and do not represent the views of UNOS/OPTN.
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Jan 4, 2012
Erick N Viorritto + 2
Open Access