IgE‐independent atopic dermatitis is associated with a β‐2 adrenergic receptor gene polymorphism

Abstract

IgE levels are not elevated in about 20% of patients with atopic dermatitis (AD). In this intrinsic AD (IAD), allergic mechanisms are not very important and pathogeny could be mainly neurogenic. β2‐adrenergic receptors are localized on cells involved in AD: Langerhans' cells, keratinocytes and lymphocytes. We wondered whether IAD could be associated with gene polymorphisms 16 and 27 of this receptor. We studied 98 healthy subjects and 83 subjects suffering from DA (UKWP criteria). IgE levels were normal in 12 of them and elevated in 71 (EAD). After DNA extraction, the genotyping was done by PCR and Direct Sequencing of candidate gene. Statistical analysis was performed with EPI‐INFO 6.04 for χ2 test. We found a significant association of Gln27Glu polymorphism with IAD (P = 0.00071 and χ2 = 14.51). There was no difference between healthy subjects and EAD patients. Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation, through the inhibition of interleukin‐2 release. It is known that catecholamines inhibit the antigen‐presenting capability of epidermal Langerhans' cells. Long‐term agonist‐promoted downregulation of receptor number is absent when glu is at position 27. We suggest that the suppression of inhibiting effects of catecholamines could be involved in IAD pathogeny. Dichotomic nature of AD (EAD and IAD) is also associated with polymorphisms (SNP) of the interleukin‐4/interleukin‐13 receptor gene and the differences of cutaneous variables (transepidermal water loss, capacitance and pH). Altogether, these findings indicate that IAD patients exhibit phenotypic and also genotypic features which differ from those patients with EAD. Otherwise, the presence of this polymorphism could provide an explication of rarity of hypertension with AD, because Glu27Gln has been identified as a susceptibility polymorphism for HTA.