No abstract

The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy.

Dasatinib is a multitargeted drug that blocks several tyrosine kinases. Apart from its well-known antileukemic activity, the drug has attracted attention because of potential immunosuppressive and antiinflammatory effects. We report that dasatinib at 1 M completely blocks antiIgE-induced histamine release in blood basophils in healthy donors, and allergeninduced release of histamine in sensitized individuals. In addition, dasatinib inhibited Fc⑀RI-mediated release of IL-4 and IgE-mediated up-regulation of CD13, CD63, CD164, and CD203c in basophils.

Der p 21 is a new important mite allergen which is liberated into the environment via faecal particles and hence may be associated with allergic asthma.

Systemic mastocytosis (SM) is a myeloid neoplasm involving mast cells (MCs IntroductionMastocytosis is a term collectively used for disorders characterized by abnormal growth and accumulation of tissue mast cells (MCs) in one or more organ systems. [1][2][3][4][5] Cutaneous as well as systemic variants of the disease have been described. [1][2][3][4][5] Systemic mastocytosis (SM) represents a persistent clonal disorder of MCs characterized by the involvement of one or more visceral organs with or without skin involvement. [3][4][5] In a majority of all patients, the transforming KIT mutation D816V is detectable. [6][7][8][9][10][11][12] This mutant is expressed in MCs as well as in MC progenitors in most cases, and is considered to play a predominant role for survival and growth of malignant cells in SM. [6][7][8][9][10][11][12][13] Therefore, KIT D816V has been recognized as a potential target of therapy in SM. [14][15][16][17][18] Notably, several efforts have recently been undertaken to identify new tyrosine kinase (TK) inhibitors that counteract phosphorylation of KIT D816V and thus the growth of neoplastic MCs. [14][15][16][17][18][19][20] Indeed, several of the new TK inhibitors have been described to counteract malignant cell growth in patients with aggressive SM (ASM) or mast cell leukemia (MCL). [17][18][19][20][21][22][23] These inhibitors include midostaurin (PKC412), nilotinib (AMN107), and dasatinib. [17][18][19][20][21][22][23] However, the first clinical data suggest that long-lasting responses cannot be achieved in all patients with such inhibitors, at least when applied as single drugs. 18 Therefore, several attempts have been made to identify additional targets in neoplastic MCs, and to develop new treatment strategies. [14][15][16] One promising approach may be to investigate survival/death-related molecules that are expressed in neoplastic MCs. 14,[24][25][26][27][28][29] In fact, several members of the Bcl-2 family have been described to be expressed in neoplastic MCs in SM and have been implicated in malignant cell growth. [24][25][26][27][28][29] It has also been described that targeting of Bcl-2 family members, such as Mcl-1, in neoplastic MCs is associated with decreased survival and growth arrest. 29 Several lines of evidence suggest that antiapoptotic members of the Bcl-2 family can bind to and can be neutralized by "proapoptotic" Bcl-2 family members such as Bim. [30][31][32][33][34] In fact, Bim is a BH3-only protein of the Bcl-2 family that acts proapoptotically in various tissues and cells. [30][31][32][33][34] It has also been described that expression of Bim is suppressed in neoplastic cells in various myeloid neoplasms, and that re-expression of Bim in these cells is associated with decreased survival and apoptosis. [35][36][37][38] Recently, Möller et al have shown that the KIT ligand stem cell factor (SCF) promotes MC survival by depressing the expression and function of Bim. 39 However, so far, expression of Bim has not been analyzed in the context of mastocytosis.In the pres...