Immunotherapy tolerance

Diet should be modified only in cases where foods have been proven to elicit symptoms. Patients with mastocytosis and Hymenoptera venom exposure are at risk for severe anaphylaxis. Thus, specific immunotherapy should be considered in patients with Hymenoptera venom allergy and then administered under close supervision [31]. The majority of patients with mastocytosis reportedly tolerate immunotherapy without significant side effects and appear protected following this approach [33,40]. However, there does appear to be some increased risk for adverse reactions during initiation of immunotherapy, as well as for therapy failures [31, 33]. An increased maintenance dose of insect venom has been reported to carry better success rates by sting provocation [41]. Also, in the light of 2 fatal cases of anaphylaxis after discontinuation of SIT in patients with mastocytosis [30], lifelong immunotherapy should be considered [26]. 

In rare cases, initiation of specific immunotherapy with insect venom leads to recurrent anaphylaxis, even with antihistamine premedication. In those cases, comedication with omalizumab (anti-IgE) has been reported to induce tolerance. In a case of recurrent anaphylaxis to induction of specific immunotherapy, the injection of 300 mg of omalizumab between 4 days and 1 h reportedly led to tolerance [42]. This approach also appears worthy of consideration in patients with both idiopathic recurrent anaphylaxis and mastocytosis who do not respond to standard antimediator therapy, as has been described in 2 atopic patients with ISM [43]. Most patients with mastocytosis and idiopathic anaphylaxis, however, are sufficiently controlled by standard antimediator therapy with antihistamines with or without low-dose corticosteroids. 

Patients who may benefit from allergen immunotherapy include those who do not tolerate traditional drug therapy (e.g., nosebleeds with intranasal steroids or sedation with antihistamines), suffer from severe symptoms, have comorbid conditions (e.g., asthma or sinusitis), fail drug therapy, or prefer not to take long-term medication. 

Because immunotherapy is expensive, has potential risks, and requires a major time commitment from patients, it should only be considered in select patients. Good candidates include patients who have a strong history of severe symptoms unsuccessfully controlled by avoidance and pharmacotherapy and patients who have been unable to tolerate the adverse effects of drug therapy. Poor candidates include patients with medical conditions that would compromise the ability to tolerate an anaphylactic-type reaction, patients with impaired immune systems, and patients with a history of nonadherence to therapy. 

Regulatory T-cell immunotherapy for tolerance to self antigens and alloanti-gens in humans. Nat Rev Immunol 2007 7 585-598. 

Takabayashi K, Tibet L, Chisholm D, Zubeldia J, Horner AA Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice. J Immunol 2003 170 3898-3905. 

Peripheral T-Cell Tolerance in Allergen-Specific Immunotherapy... 

Peptide immunotherapy (PIT) is another attractive approach for investigation of peripheral T-cell tolerance in humans. Short allergen peptides, either native sequences or altered peptide... 

Akdis CA, Akdis M, Blesken T, Wymann D, Alkan SS, Muller U, et al Epitope specific T-cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest 1996 98 1676-1683. 

Frick OL, Teuber SS, Buchanan BB, Morigasaki S, Umetsu DT Allergen immunotherapy with heat-killed Listeria monocytogenes alleviates peanut and food-induced anaphylaxis in dogs. Allergy 2005 60 243-250. Stock P, Akbari 0, DeKruyff RH, Umetsu DT Respiratory tolerance is inhibited by the administration of corticosteroids. J Immunol 2005 175 7380-7387. 

Bohle B, Kinaciyan T, Gerstmayr M, Radakovics A, Jahn-Schmid B, Ebner C Sublingual immunotherapy induces IL-lO-producing T regulatory ceUs, allergen-specific T-ceU tolerance, and immune deviation. J Allergy Clin Immunol 2007 120 707-713. ... 

While on the one hand the aspects of Tregs and tolerance induction in allergen-specific immunotherapy and different procedures of vaccination are described, one chapter is added which describes future possibilities of stem cell transplantation in genetically linked disorders. 

It is noteworthy that MHC class I downregulation is not the only escape mechanism available for tumors to avoid T cell responses other mechanisms such as downregulation of the tumor antigens, alterations of the apoptosis program, expression of inhibitory molecules, lack of expression of costimulatory molecules leading to immunological tolerance have been also described. The identification of defined immune escape mechanisms in human or mouse tumors point to the existence of active immunosurveillance which is important for the implementation T cell-based immunotherapy protocols. This information will further help to select patients suitable for such therapies. Furthermore, restoration of the tumor MHC class I phenotype to a normal MHC phenotype may be an other strategy to restore an efficient immune response in cancer patients. All these approaches are still hypothetical and no clinical procedures have been tested so far. 

More than 90% of patients with myasthenia gravis have circulating antibodies directed against a subunit of the acetylcholine receptor/ Immunosuppressive drugs and steroids help to cut down on these autoantibodies, and many patients are benefit-ted by removal of the thymus. Newer approaches involve specific immunotherapy aimed at increasing tolerance to either T cells or to B cells.C/d For example, oral ingestion of purified acetylcholine receptors to desensitize the body s response or inhibition of production of 11-2. 

Clinical tolerance to allergens may be achieved by the administration of allergen extracts, which is called specific immunotherapy. In addition to its therapeutic value, it has been suggested that this treatment may also alter the progression of disease. Specific allergen immunotherapy (SIT) is used to alleviate the condition associated... 

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