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, Vbeta2 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 Vbeta2 and Vbeta3 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 Vbeta2 T cell infiltration. HSV-stimulated PBMC obtained at these times had an altered TCR repertoire characterized by a predominance of Vbeta2 cells. The duration of viral gene expression, Vbeta2 cell infiltration and altered TCR repertoire usage correlated with the duration of clinical symptoms.


CONCLUSIONS
The data suggest that HSV and a virus-specific immunopathology component are involved in the causation of all HAEM episodes experienced by the patient.
Kokuba
H
H
Virology/Immunology Laboratories, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Imafuku
S
S
Burnett
J W
JW
Aurelian
L
L
D000328:Adult; D004892:Erythema Multiforme / Q000209:etiology* / Q000276:immunology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D015751:Genes, pol / Q000235:genetics; D006561:Herpes Simplex / Q000150:complications* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology; D017193:Skin Diseases, Viral / Q000209:etiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D011948:Receptors, Antigen, T-Cell