Comparative analysis of IL6 and IL6 receptor gene polymorphisms in mastocytosis

Mastocytosis is a rare disease with reported high interleukin-6 (IL6) levels influencing disease severity. The present study investigated polymorphisms within the genes that encode IL6 and its receptor (IL6R) in relation to mastocytosis development in a case-control design. Analysis of the IL6R Asp358Ala polymorphism showed that carriers of the AA genotype had a 2.5-fold lower risk for mastocytosis than those with the AC or CC genotypes. No association with mastocytosis was found for the IL6-174G/C polymorphism, however, it may influence the effect of IL6R polymorphism. To the best of our knowledge this is the first study analysing IL6/IL6R polymorphisms in mastocytosis

Diagnosis, classification and management of mast cell activation syndromes (Mcas) in the era of personalized medicine

Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE‐dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA‐related symptoms range from mild to severe to life‐threatening. The severity of MCA‐related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual´s baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC‐stabilizing or mediator‐targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT‐mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE‐dependent allergy or other reactive MCA‐triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT‐mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT‐mutated MCs, IgE‐dependent allergies and sometimes HAT are detected. These patients may suffer from life‐threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE‐blocking antibodies, anti‐mediator‐type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co‐morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine

Diagnosis, classification and management of mast cell activation syndromes (MCAS) in the era of personalized medicine

Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where; KIT; -mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor; KIT; -mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where; KIT; -mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine

Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis

P>Background: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. Methods: Whole-genome gene expression analysis was performed in peripheral blood cells. Results: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P <0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naive Bayes prediction model was built identifying patients with IVA. Conclusions: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions

Molecular background, clinical features and management of pediatric mastocytosis: Status 2021

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self\u2010limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small\u2010sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator\u2010related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto\u2010injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow\u2010up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood