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This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII gene impairing the binding to VWF are a common cause of mild/moderate hemophilia A. The implications of these observations for the treatment of patients with coagulation factor concentrates and desmopressin are discussed.

Background: Major allergens could represent a ‘port of entry’ to allergen polysensitization. The immunogenic properties of Der p 2 T cell epitopes were evaluated to test this hypothesis. Material and Methods: T cells were obtained from regional lymph nodes of mice belonging to four different haplotypes and used in proliferation assays using Der p 2 or synthetic peptides. Results: T cells from recombinant (r) Der p 2-immunized Balb/c mice (H-2d) proliferated to an immunodominant region encompassing residues 21–35, which also stimulates T cells of mice expressing three alternative haplotypes (H-2b, H-2k and H-2s), indicating the presence of a universal T cell epitope. Epitope mapping identified Ile28 as a critical H-2-binding residue for all four different haplotypes. p21–35 presents a sequence homology with FIS, another universal T cell epitope. FIS priming boosts immune responses to distinct weak immunogens. Balb/c mice primed with p21–35 or FIS produced stronger immune responses to transferrin upon administration of the latter than unprimed mice. Besides, this procedure profoundly affected the overall B cell response to rDer p 2. Conclusion: An immunodominant T cell epitope of Der p 2 behaves as a universal epitope and enhances responses to related and unrelated coadministered antigens. These findings have implications for the understanding of allergen polysensitization and for immunotherapy.

Administration to allergic patients of complexes made of allergen and anti-allergen antibodies results in a reduction in the levels of specific IgE and IgG antibodies that is limited to antibodies present in the complexes. The epitope-specific nature of this reduction is demonstrated by taking advantage of the cross-reactivity between Der p I and Der f I. In addition, an increased production of anti-idiotypic antibodies is demonstrated. As such treatment significantly improves patients with allergic asthma or atopic dermatitis, it may represent a valuable alternative to conventional immunotherapy.