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 recur rent 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 g ene expression, V beta 2 T cell infiltration of lesional skin and altered T cell receptor (TCR) repertoire usage by HSV-stimulated peripheral blood mo nonuclear cells (PBMC). However, HAEM recurrences are not always preceded b y overt HSV eruptions and virus cannot be isolated from HAEM lesional skin. Therefore, it is unknown whether all HAEM recurrences experienced by a giv en patient are HSV related. Objective: The studies described in this report were designed to examine whether all HAEM recurrences experienced by a giv en patient are HSV related. Methods: We describe one patient who was studie d longitudinally during 6 HAEM recurrences and in the intervening lesion-fr ee periods. Lesional skin from all HAEM episodes was studied for HSV gene e xpression 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 exp ression (RNA and protein) as well as V beta 2 T cell infiltration, HSV-stim ulated PBMC obtained at these times had an altered TCR repertoire character ized by a predominance of V beta 2 cells. The duration of viral gene expres sion, V beta 2 cell infiltration and altered TCR repertoire usage correlate d with the duration of clinical symptoms. Conclusion: The data suggest that HSV and a virus-specific immunopathology component are involved in the cau sation of all HAEM episodes experienced by the patient.