Positive correlation of anti-herpes simplex type I virus antibody levels with pemphigus vulgaris disease status and activity in a large patient cohort

Background: It is well accepted that pemphigus vulgaris (PV) is genetically linked to specific HLA class II subtypes. Environmental factors, including the role of herpes simplex virus (HSV1) in disease manifestation, have also been implicated, but in a limited number of patients and with inconsistent results. Objectives: To clarify an association between HSV1 and PV in a large data set, including a stratification by dynamic and static clinical parameters, including disease activity, therapy status, HLA association, and gender. Materials & methods: Serum HSV1 IgG levels from PV patients and healthy controls were measured by ELISA. Subjects were typed for HLA class II DRB1 and DQB1 alleles, and categorized as HLA-matched if homozygous or heterozygous for either one of the known PV-susceptibility alleles, DRB1*0402 and DQB1*0503. Results: Our data indicate that PV patients carry significantly higher levels of anti-HSV1 antibodies than healthy controls, and that this effect was more pronounced in the active phase of disease when compared to remission. A mild positive association could also be observed for carriers of the PV-associated HLA alleles versus HLA-unmatched controls, as well as for female PV patients when compared to female control subjects. Conclusion: Our data suggest a role of HSV1 in the expression of PV and further show that HLA status and gender may influence HSV1 susceptibility and/or expression of anti-HSV1 antibodies. Additional research with larger datasets is required to determine whether HSV is causally linked to PV pathogenesis and conclusively link HLA status and gender to HSV1 antibody levels.