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Complotypes in pemphigus vulgaris: differences between Jewish and non-Jewish patients
Insights
Certain genetic profiles, known as complotypes, are more common in pemphigus vulgaris patients. These complotypes likely indicate linked genes on the major histocompatibility complex that increase disease susceptibility.
Area of Science:
- Immunogenetics
- Human Genetics
- Molecular Biology
Background:
- Major histocompatibility complex (MHC) genes, including BF, C2, C4A, and C4B, are inherited in linked sets called complotypes.
- Complotypes are highly polymorphic genetic units.
- Several complotypes occur at frequencies above 0.01 in Caucasian populations.
Purpose of the Study:
- To investigate the association between specific complotypes and the autoimmune blistering disease, pemphigus vulgaris.
- To determine if complotype frequencies differ between pemphigus vulgaris patients and healthy controls.
Main Methods:
- Comparison of complotype frequencies in pemphigus vulgaris patients (Ashkenazi Jewish and non-Jewish Caucasian) with general Caucasian controls.
- Statistical analysis to calculate relative risks associated with specific complotypes.
Main Results:
- The complotypes SC21 and SB45 were significantly elevated in pemphigus vulgaris patients compared to controls.
- SC21 was elevated exclusively in Ashkenazi Jewish patients (relative risk = 17).
- SB45 was elevated solely in non-Jewish Caucasian patients (relative risk = 57).
Conclusions:
- Elevated complotype frequencies in pemphigus vulgaris are unlikely due to the complotype genes themselves conferring susceptibility.
- These complotypes likely serve as markers for extended MHC haplotypes with fixed DNA.
- Susceptibility to pemphigus vulgaris is probably conferred by class II genes located on these associated MHC haplotypes.
Abstract:
Haplotypes of alleles of the major histocompatibility complex (MHC) complement genes BF, C2, C4A, and C4B are inherited as single highly polymorphic genetic units called complotypes. There are about a dozen complotypes with frequencies above about 0.01 in Caucasians. In the blistering disease pemphigus vulgaris, the complotypes SC21 and SB45 were found to be markedly elevated in patients compared with general Caucasian controls. The SC21 increase was in Ashkenazi Jewish patients exclusively (relative risk = 17 in that population), whereas SB45 was found solely in non-Jewish Caucasians (specific population relative risk = 57). Although these are unusually high relative risks, it is most unlikely that these complotypes represent susceptibility genes for pemphigus vulgaris. Rather, it is probable that they mark extended major histocompatibility complex haplotypes with fixed DNA so that independent examples in the population have the same alleles. It is likely that it is the class II genes on these haplotypes that confer susceptibility.