Association of HLA-Bw65 with two major complotypes

Area of Science:

• Immunogenetics
• Human Leukocyte Antigen (HLA) complex
• Complement system genetics

Background:

• The human leukocyte antigen (HLA) system plays a crucial role in immune response.
• Complement allotypes, including C2, Bf, and C4, are genetically determined and linked to HLA regions.
• Understanding associations between HLA subtypes and complement allotypes is vital for immunological research.

Purpose of the Study:

• To investigate the association between HLA-B14 subtypes, specifically Bw64 and Bw65, and various complement allotypes (C2, Bf, C4).
• To characterize the genetic makeup of haplotypes carrying HLA-Bw64 and HLA-Bw65 in a population and within families.
• To identify potential structural variations, such as duplications, within the complement loci linked to these HLA subtypes.

Main Methods:

• Population-based study involving allotyping of C2, Bf, C4A, and C4B in unrelated subjects positive for HLA-Bw64 or HLA-Bw65.
• Family studies to characterize HLA-ABC, DR, DQ antigens, and complement allotypes on HLA-Bw65 bearing haplotypes.
• Utilized an anti-C4B monoclonal antibody for detailed analysis of C4B gene products and locus duplications.

Main Results:

• The complement haplotype associated with HLA-Bw64 was identified as BfS, C4A2, C4B2.
• Two major complement haplotypes were associated with HLA-Bw65: (i) C2C, BfF, C4A3, C4A1 and (ii) C2C, BfS, C4A2, C4B2.
• Family studies revealed a C4B2B1 duplication of the C4B locus in HLA-Bw65 bearing haplotypes, with three C4B gene products identified in affected individuals.

Conclusions:

• The study establishes specific complement allotype associations for HLA-Bw64 and HLA-Bw65.
• A significant finding is the high prevalence of C4B locus duplication in HLA-Bw65 bearing haplotypes.
• It is proposed that most, if not all, HLA-Bw65 haplotypes may carry this C4B locus duplication, suggesting a potential structural characteristic of these haplotypes.