Longitudinal study of a patient with herpes-simplex-virus-associated erythema multiforme: Viral gene expression and T cell repertoire usage

Background: Erythema multiforme is a polymorphous self-limited, often recurrent eruption that can follow herpes simplex virus (HSV) infection, hereby designated HAEM. Studies of relatively large groups of patients during one recurrent episode indicated that HAEM pathogenesis is associated with HSV gene expression, V beta 2 T cell infiltration of lesional skin and altered T cell receptor (TCR) repertoire usage by HSV-stimulated peripheral blood mononuclear cells (PBMC). However, HAEM recurrences are not always preceded by overt HSV eruptions and virus cannot be isolated from HAEM lesional skin. Therefore, it is unknown whether all HAEM recurrences experienced by a given patient are HSV related. Objective: The studies described in this report were designed to examine whether all HAEM recurrences experienced by a given patient are HSV related. Methods: We describe one patient who was studied longitudinally during 6 HAEM recurrences and in the intervening lesion-free periods. Lesional skin from all HAEM episodes was studied for HSV gene expression and infiltration by V beta 2 and V beta 3 T cells. PBMC obtained at these times were assayed for TCR repertoire usage upon HSV stimulation. Results: Lesional skin from all HAEM episodes was positive for HSV gene expression (RNA and protein) as well as V beta 2 T cell infiltration, HSV-stimulated PBMC obtained at these times had an altered TCR repertoire characterized by a predominance of V beta 2 cells. The duration of viral gene expression, V beta 2 cell infiltration and altered TCR repertoire usage correlated with the duration of clinical symptoms. Conclusion: The data suggest that HSV and a virus-specific immunopathology component are involved in the causation of all HAEM episodes experienced by the patient.