USMLE Reviewer
(By Subscription)
Immunologic, genetic, and environmental factors all seem to play a role [26-28].
The human leukocyte antigen (HLA) region as well as polymorphisms in other immune-related genes are associated with IgAV, sometimes with conflicting results, which could be due to differences in ethnic and environmental factors [29,30]. There are numerous case reports of IgAV occurring after vaccination, and a case-control study found an increased risk of IgAV within 12 weeks after vaccination with the measles-mumps-rubella (MMR) vaccine (odds ratio [OR] 3.4, 95% CI 1.2–10.0) but not with other vaccines [31]. The absolute risk was low, though (2.8 percent of cases had MMR within 12 weeks of developing IgAV compared with 1 percent of controls). A case-crossover study of 167 children found no increased risk of IgAV within three months of receiving a vaccine compared with the three months prior to that (OR 1.6, 95% CI 0.8-3.0) [32]. Similar results were seen for IgAV risk within 1, 1.5, or 2 months of vaccination. These results suggest that vaccinations are not a major etiologic factor in IgAV and therefore should not be avoided.
Attention has focused on the potential role of increased serum levels of IgA and IgA immune complexes in the pathogenesis of IgAV. In addition, several studies report alterations in the glycosylation of IgA, elevated levels of IgA anticardiolipin antibodies, and increased levels of transforming growth factor (TGF) beta in patients with IgAV [13,33-37]. The fact that only one of the two IgA subtypes (IgA1, but not IgA2) is found in the inflammatory infiltrates of this disease remains unexplained [38,39]. Similarly, the precise role of IgA and the specific involvement of IgA1 in the pathogenesis of IgAV remain unclear. Some research suggests that IgA anticardiolipin antibodies may play a role [33,40,41]. Results from one study suggest that beta-2-glycoprotein I (beta-2GPI) is an antigenic target for IgA [42]. Despite the increased presence of these antibodies, there are few reports of thrombosis. Activated neutrophils and increased production of interleukin (IL) 8 may also play a role [43].
(By Subscription)