Uncommon DR7-DR53-DQ haplotypes in four canadian subjects

• Published in: Human immunology Vol. 76; p. 151
• Main Authors: Sidahmed, Abubaker Me, Stamm, Luz, Randrup, Kasia, McKinley, Connie, Rahmanian, Taleb, Zeeben, Sharon, William, Jolene, Wang, Ling Ling, Kostur, Carrera, Khan, Faisal, Berka, Noureddine
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2015
• Subjects: Allergy and Immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2015.07.210

Aim To describe uncommon DR7-DR53-DQ haplotypes in four Canadian subjects that deviate from the frequent common association between DR7, DR53 and DQ antigens. Methods Medium resolution HLA typing for HLA- DRB1, DRB3/4/5 and DQB1 loci were performed using Luminex based SSO kits (One Lambda Labtype). A high resolution typing using SSP for DRB4 (Olerup SSP kit) and SBT for DRB1 and DQB1 (Life Technologies) were further performed to evaluate these uncommon haplotypes. Results We detected presence of DRB4 ∗ 01:01 instead of more frequent DRB4 ∗ 01:03N in association with the DR7 and DQ9 haplotype in two Canadian subjects. Furthermore, we also detected DRB4 null allele in association with DR7 and DQ2 in a kidney transplant recipient and a bone marrow patient (Table 1). Conclusion Here, we report two cases of DRB1∗07, DRB4∗01, DQB1∗03:03 haplotype and two cases of DRB4∗01:03N null allele in association with DRB1 ∗ 07:01 and DQB1 ∗ 02:02 haplotype . Our findings are in disparity to reported common linkages in which DR7- DQ9 haplotype is commonly seen in association with the null allele DRB4 ∗ 01:03:01:02N . There are 15 alleles of DRB4; 12 of them produce an expressed DR53 antigen and 3 resulting in null alleles. The presence of these rare haplotypes might be due to unidirectional or bidirectional homologous recombination event that happened between the DR7, DR53, DQ2 and the DR7, DR53- null, DQ9 haplotypes. This is supported by the presence of reported DR7-DQ2 haplotype with a DRB4 null allele. It might also be due to point mutation in DRB4∗01:03:01 changing the splice site in case of DR7, DR53null, DQ2 haplotype. Understanding the genetics and expression of DRB4 gene is of clinical relevance in the hematopoetic stem cell transplant, both GVHD and graft rejection, in solid organ transplant especially effect of donor specific antibodies, and in disease association with autoimmune disorders, such as celiac, Crohn’s disease, myasthenia gravis, rheumatoid arthritis, Hashimoto’s thyroiditis, vitiligo, primary biliary cirrhosis and ALL in children.