Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions

• Published in: Allergy (Copenhagen) 2000-11, Vol.55 (11), p.998-1004
• Main Authors: BLANCA, M, POSADAS, S, TORRES, M. J, LEYVA, L, MAYORGA, C, GONZALEZ, L, JUAREZ, C, FERNANDEZ, J, SANTAMARIA, L. F
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; b-lactam antibiotics; Biological and medical sciences; captopril; Drug Hypersensitivity - immunology; Drug toxicity and drugs side effects treatment; Exanthema - immunology; Female; histocompatibility antigen HLA; HLA-DR Antigens - analysis; homing receptors; Humans; Male; Medical sciences; Membrane Glycoproteins - analysis; metronidazol; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; phenytoin; propyphenazone; Rats; Receptors, Lymphocyte Homing - analysis; spiramycin; T-Lymphocytes - chemistry; tiazide
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1034/j.1398-9995.2000.00628.x

In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor. We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms. These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.