Human neutrophil antigen-2 is located on a glycosylphosphatidylinositol-anchored receptor, CD177. Humans not expressing CD177 on their neutrophils may, under defined conditions, form isoantibodies. The genetic background for the absence of CD177 is not fully understood, and genetic screening of patients and donors is currently unavailable. A recent study has documented two mutations associated with CD177 absence: a nonsense polymorphism c.843A>T and a single-base deletion c.1011delG.STUDY DESIGN AND METHODS:
First, we aimed to demonstrate that these newly described mutations are indeed associated with the absence of CD177. DNA fragments from isoimmunized, CD177-negative individuals were sequenced (n = 5). An additional five negative and 10 positive individuals were also analyzed. Second, we aimed to establish a sequence-specific primer (SSP) polymerase chain reaction method for easy and rapid detection of these mutations.RESULTS:
None of 10 CD177-positive individuals, but four of 10 CD177-negative individuals were homozygous for the A>T mutation at Position c.843, including three of five isoimmunized individuals. This finding is supportive for the reported association. Surprisingly, and in contrast to the initial report, c.1011delG was not detected in our cohort. Furthermore, a two-step SSP method for c.843A>G was successfully established.CONCLUSION:
c.843A>T, but not c.1011delG, is associated with the absence of CD177 in a significant number of individuals, including CD177-isoimmunized women. The c.843A>T mutation is easily detectable by a newly established SSP, but screening for this mutation will only provide sufficient evidence for a final diagnosis in case of homozygosity for the c.843T allele.