DRB4 NULL ALLELE ALSO IN DR4 POSITIVE INDIVIDUALS
Christina EM Voorter and Ella M van den Berg-Loonen. Tissue Typing Laboratory, University Hospital Maastricht, Maastricht, The Netherlands.

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The DRB4 null allele, DRB4*0103102N, contains a point mutation in the acceptor splice site of intron 1 compared with the normally expressed allele DRB4*0103101. This mutation prevents the correct processing of the DRB4 gene transcript and results in the absence of protein expression at the cell surface. This implicates that the DR53 antigen is not serologically detected when the null allele is present. Up to now absence of DR53 and presence of DRB4*0103102N has only been demonstrated in DR7-DQ9 positive individuals and it was thought that all DRB1*04 and DRB1*09 positive individuals express the DR53 protein on the cell surface of the class II positive cells. However, we have recently detected the DRB4 null allele in two families, in which the null allele segregated with DRB1*0404.

In one family the presence of the DRB4 null allele was serologically obscured by the presence of a second DRB4 allele, DRB4*0103101. The detection of the null allele was accomplished by both PCR-SSP and SBT. For SSP primer mixes were used that discriminated between DRB4*0103101 and DRB4*0103102N. With SBT the 3' part of the intron 1 sequence was obtained, identifying the presence of DRB4*0103101, DRB4*0103102N or both.

In the other family the absence of DR53 was serologically suggested, but different from DR7-DQ9 positive, DR53 negative individuals. The difference in reaction pattern could be explained by the use of polyspecific sera, one obviously reacting with DR4 and DR53 and the other reacting with DR7 and DR53. The absence of DR53 in this family was confirmed by PCR-SSP and SBT, both detecting the DRB4*0103102N allele.