Expression of α-defensin 1-3 in T cells from severe cutaneous drug-induced hypersensitivity reactions.
BACKGROUND
Cytotoxic T cells seem to be the main effector cells in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). However, recent data support a role of the innate immune system in the etiopathology of drug-induced cutaneous reactions. In this study, we analyzed the expression of α-defensins 1-3 in mononuclear cells from patients with SJS/TEN, drug-induced maculopapular exanthema (MPE), and healthy donors.


METHODS
DEFA1A3 gene expression was analyzed by quantitative and end-point RT-PCR. Intracellular flow cytometry, immunofluorescence and immunohistochemistry were carried out to verify α-defensin 1-3 protein expression in mononuclear cells from peripheral blood and skin infiltrates. α-Defensin 1-3 concentration was evaluated in plasma and blister fluid samples by ELISA.


RESULTS
We herein describe DEFA1A3 gene expression in peripheral blood mononuclear cells (PBMCs) from patients with drug-induced cutaneous diseases. Gene expression analysis unveiled transcription in CD4 and CD8 peripheral blood T cells. Protein expression was confirmed by intracellular flow cytometry in mononuclear cells from the patients, including monocytes, NK cells, and T cells from peripheral blood and blister fluid. Further analysis of protein content by flow cytometry revealed higher protein levels in CD56(+) CD3(+) lymphocytes from patients with SJS/TEN when compared to MPE and healthy donors. Immunohistological analysis was used to confirm expression in dermal infiltrates. α-Defensin levels were estimated by ELISA to be 3- to 175-fold higher in blister fluid when compared to simultaneously drawn plasma samples.


CONCLUSIONS
Upregulation of innate immune molecules such as α-defensins 1-3 in T cells from patients with SJS/TEN may be involved in the etiopathology of these life-threatening diseases induced by medications.
Morel
E
E
Research Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
Alvarez
L
L
Cabañas
R
R
Fiandor
A
A
Díaz
R
R
Escamochero
S
S
Prior
N
N
Blanca
M
M
Bellón
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010267:Parapsoriasis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult; D023084:alpha-Defensins / Q000235:genetics* / Q000276:immunology*
D018950:Lipopolysaccharide Receptors; D023084:alpha-Defensins