Presence of DRB4*0103102N null allele in association with HLA DRB1*0701/DQB1*0202 haplotype

A. Morabito, L. Delfino, A. Longo, C. Pera and G.B. Ferrara. National Cancer Institute, IST, c/o Advanced Biotechnology Center, ABC, Genoa, ITALY.

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HLA-DRB4 gene is usually associated with HLA-DR4, HLA-DR7 and HLA-DR9 positive haplotypes, resulting in DR53 antigen with the exception of DRB4* 0103102N, DRB4* 0201N and DRB4 0301N. These alleles contain deletions or [AL1] mutations and consequently do not encode cell surface products. In the last years, the number of the detected HLA-DRB4 alleles has rapidly increased, probably due to the widely used DNA molecular typing strategies. At the present, 9 DRB4 alleles have been described. 

HLA DRB4* 0103102N null alleles was reported to be in association with DR7/DQ9 haplotype and has been recently found in different DR4-positive individuals.

HLA class II high resolution typing by PCR using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT) of an healthy blood donor from Centro Ricerche Immunoematologiche AVIS Bergamo revealed the presence of DRB4* 0103102N null allele segregating with DRB1*0701 and DQB1*0202.

This unusual association disagrees with the most common haplotype DRB1*07/ DQB1*0303/ DRB4*0103102N null allele and it may be originated from a single point mutation at the splice site at the end of the first intron.