MHC determinants of response to Rh immunization

Area of Science:

• Immunogenetics
• Human immunology
• Molecular genetics

Background:

• Immune response genes controlling antibody production are challenging to identify in humans.
• Evidence in mice and guinea pigs suggests Major Histocompatibility Complex (MHC)-linked genes influence immune response specificity and magnitude.
• Features of the anti-Rh D antibody response suggest involvement of limited immune response genes.

Purpose of the Study:

• To investigate the association between MHC-linked complement genes and the immune response to Rh D antigen.
• To identify specific genetic markers related to anti-Rh D antibody production in humans.

Main Methods:

• Genetic typing of four MHC-linked complement genes (BF, C2, C4A, C4B) was performed.
• Analysis included 52 Caucasian individuals with anti-D titers and a control population of 623 chromosomes.
• Allele frequencies were compared between patient and control groups.

Main Results:

• Increased frequencies of BF F1, C4A 3, and C4B Q0 alleles were observed in individuals with anti-D antibodies.
• These alleles constitute a common complotype (BF F1, C2 C, C4A 3, C4B Q0) found on a 6p haplotype.
• This complotype is associated with the immune response to Rh D and is also increased in patients with insulin-dependent diabetes mellitus and membranous glomerulonephritis.

Conclusions:

• A specific extended haplotype on chromosome 6p, containing the complotype BF F1, C2 C, C4A 3, C4B Q0, is strongly associated with the immune response to Rh D.
• This genetic association provides insight into the genetic control of human immune responses.
• The complotype's association with other diseases suggests a broader role in immune system regulation.