Gene expression analysis of histamine receptors in peripheral blood mononuclear cells from clinically-isolated syndrome and multiple sclerosis patients

Abstract

Classically envisioned as a key mediator in allergic reactions, histamine has been recently suggested to play a role in central nervous system (CNS) autoimmune responses occurring in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), animal model for this disease. Studies performed with histamine receptors or histidine-decarboxylase knockout mice have shown that histamine can play promoting or protective roles in EAE depending on the receptors engaged. Moreover, transcript levels of histamine receptors are significantly modulated in peripheral T cells in different stages of EAE. In order to determine whether these findings could be of relevance for the human disease, in the present study we analysed the gene expression of histamine receptor 1 (HRH1), HRH2 and HRH4 in peripheral blood mononuclear cells derived from patients with clinically isolated syndrome (CIS), relapsing–remitting (RR), secondaryprogressive (SP), primary-progressive (PP) MS, and healthy controls (HC). HRH3 has not been included in our study, as its expression is restricted to the CNS. Histamine receptors were all expressed at mRNA level and HRH2 transcripts were always more abundant than those for HRH4 and HRH1 in the analysed groups. Interestingly, we found that HRH1 transcript was significantly downmodulated in SP-MS compared with HC (p b 0.05), and HRH4 was increased in this group compared to HC (p b 0.05), CIS (p= 0.01) and SM-RR (p b 0.05). No other differences in the expression of histamine receptors were observed between HC, CIS or other clinical forms of definite MS. These results show that histamine receptors are differentially expressed in SP-MS.