Impact of allergic rhinitis and specific subcutaneous immunotherapy on peripheral blood basophils of patients sensitized to Dermatophagoides pteronyssinus

Abstract

BackgroundBasophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known.MethodsPeripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR.ResultsHigher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4.ConclusionPB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.

Subcutaneous immunotherapy induces alterations in monocytes and dendritic cells homeostasis in allergic rhinitis patients

“…This increase in the production of “blocking” antibodies, has been suggested to be the responsible for IgE neutralization during SIT through direct competition with IgE for allergen binding [ 11 , 13 – 15 ]. However, the topic is still under debate; firstly, because the increase in the quantity of IgG seems to occur after the first signs of therapeutic efficacy, rather than before [ 12 ]; secondly, because mucosal DCs and mast cells come directly in contact with the allergen before IgG can exert their blocking activity [ 12 ]; and, thirdly, because of the poor or non-existing correlations between IgG levels and clinical benefit [ 10 – 12 , 14 , 43 , 46 ]. Therefore, we studied the amount of receptor-bound IgE per cell, as well as the receptor-bound IgG expression in different subpopulations of APCs.…”

La farmacogenómica en el desarrollo de la inmunoterapia específica de alérgenos y autoantígenos

“…En dos estudios se mejora la comprensión de los basófilos sanguíneos en el mecanismo temprano de desensibilización alérgica de la ITAE subcutánea. De los pacientes con rinitis alérgica tratados con la ITAE de extracto alergoide Der p1 Depigoid (Leti, Madrid, España) y los controles enlazados por edad y sexo se recogió muestra de sangre periférica antes del tratamiento y 4 horas después 25 . Se realizó la RCPc de los genes de la histamina N-metiltranferasa (HNMT) y la triptasa alfa/beta 1 (TSPAB1) que están relacionados con mediadores alérgicos.…”

El gen PTGDR en la alergia: Estudio de genotipado y análisis de expresión génica

“…En este estudio los genes de referencia seleccionados fueron GAPDH y TBP, el primero está relacionado con la vía de la glicolisis y el segundo con la transcripción. El gen de referencia más estable se correspondía con TBP y el otro gen estable elegido, con respaldo bibliográfico en estudios con población alérgica, fue GAPDH (163,164). En los estudios de expresión es recomendable utilizar al menos dos genes de referencia, ya que uno sólo puede dar lugar a errores relativamente grandes (165).…”