Male Lupus Research
Many people believe lupus primarily is a female disease, since lupus is nearly nine times more common among women of childbearing age compared to males. However, evolving evidence suggests that males with lupus may have a more explosive onset of lupus, and that families that have more than one person with lupus, in which at least one is a male, will have more severe forms of lupus among all affected family members.
There have been too very few studies conducted into the cause, progression or treatment options for male lupus. To address this serious gap, the Foundation established a specific initiative to support basic and clinical high quality, original research related to expanding scientific understanding of lupus in males.
This grant award is made possible through support of the Wallace H. Coulter Foundation in memory of Michael Jon Barlin.
Women develop lupus 9 times more often than men. Research implicates hormones and having 2 X chromosomes as part the problem in women. However, little is known about why men get lupus. Part of lupus susceptibility is genetically determined, and the genes responsible are being identified rapidly. However, not everyone with lupus genes gets lupus. Identical twin studies show that if one twin gets lupus, the other has a 24% chance of also getting lupus. This lack of complete concordance indicates that something from the environment is also required. Work from our group indicates that the environment contributes to lupus by modifying how DNA is packaged in the nucleus, referred to as chromatin structure. Genes in tightly packaged DNA cannot be expressed, but are expressed if the structure is opened up and available to the molecules causing expression. The primary signal for tight DNA packaging is a modification of DNA called methylation. Methylation serves to tether proteins that maintain the condensed structure. DNA methylation in regulatory immune cells, called T cells, is defective in people with lupus, and lupus can be caused in animal models just by inhibiting DNA methylation. We hypothesize that DNA demethylation in genetically predisposed people causes lupus. We also hypothesize that men will require more lupus genes, more DNA demethylation, or both to develop lupus than women. The studies proposed will test this model, and will lead to studies preventing lupus by maintaining DNA methylation, modifying genetic risk or both.