Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA 2 LEN projectThe synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono-vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FceRI) and other factors regulating the activation of FceRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.

BackgroundWhen treating bladder cancer patients, the most significant problems usually concern cases with high-grade non-muscle-invasive carcinoma, and a better understanding of which patients would benefit from early radical cystectomy is urgently needed. The uropathology community is seeking more user-friendly approaches to distinguishing between T1 cancers exhibiting different types of clinical behavior.MethodsAfter a retrospective review, we selected a group of 314 patients who underwent transurethral resection of the bladder (TURB) and were diagnosed with high-grade urothelial carcinoma staged as T1. Three different substaging systems were applied: one was the anatomy-based T1 a/b; and two involved micrometric thresholds of either 0.5 mm of invasion (as proposed by van Rhijn et al.), or 1 mm of invasion (as proposed in the present study). Early reTUR (repeated transurethral resection) was performed in 250 patients, and the same substaging approaches were applied to cases of T1.ResultsIt proved feasible to apply the 1 mm substaging system in 100 % of cases, the van Rhijn system in 100 %, and the anatomy-based method (T1 a/b) in 72.3 % of cases. At a mean follow-up of 46 months, the recurrence-free survival rate was significantly better (p < 0.001) in the group that underwent reTUR, while none of the three substaging systems reliably predicted recurrences. The 1 mm did seem promising, however, as a threshold for predicting progression, reaching statistical significance in the Kaplan Meier estimates (p < 0.04).ConclusionOur study shows that micrometric substaging is feasible in this setting and should be extended to include any early reTUR to complete the substaging done after the first TURB. It can also provide helpful prognostic information.

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A 659 bp cDNA clone** coding for an allergen of Pj pollen has been isolated from a lambda gt 11 library, and its DNA sequence determined. The cDNA insert showed an open reading frame of 429 bp coding for an allergenic protein of 14,866 Da and a deduced amino acid sequence containing 143 residues. The expressed recombinant protein represented the major allergen Par j I since it reacted with 95% of the sera from Pj-allergic patients (n = 22) and with two Par j I-specific monoclonal antibodies. No similarity with other known DNA and protein sequences has been detected.

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Parietaria is a genus of dicotyledonous weeds of the Urticaceae family including several species and its pollen grain is one of the most important allergenic sources in the Mediterranean area. Species belonging to this genus induce IgE responses in approximately 10 million people. Identification of allergens by means of independent strategies suggest that the allergens of the two more common species, Parietaria judaica and Parietaria officinalis, show molecular weights ranging between 10 and 14 kD and that the allergens of the two extracts are highly cross-reactive. Biochemical analysis and molecular cloning allowed the isolation and immunological characterization of the two major allergens of the P. judaica pollen, Par j 1 and Par j 2. Sequence comparison suggests that the P j major allergens of P. judaica belong to the nonspecific lipid transfer protein family, and three-dimensional modeling by homology has revealed that both proteins present a very conserved structural motif composed of four α-helices. Immunological analysis has shown that Par j 1 and Par j 2 are able to bind most of the P. judaica-specific IgE and some of their IgE determinants have been mapped. Recombinant Par j 1 and Par j 2 allergens have been shown to possess immunological properties equivalent to their natural counterpart and their availability represents a fundamental tool for the diagnosis and therapy of Parietaria pollen allergy.

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