Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A significant number of contributions to our understanding of primary immunodeficiencies (PIDs) in pathogenesis, diagnosis, and treatment were published in the Journal in 2013. For example, deficiency of mast cell degranulation caused by signal transducer and activator of transcription 3 deficiency was demonstrated to contribute to the difference in the frequency of severe allergic reactions in patients with autosomal dominant hyper-IgE syndrome compared with that seen in atopic subjects with similar high IgE serum levels. High levels of nonglycosylated IgA were found in patients with Wiskott-Aldrich syndrome, and these abnormal antibodies might contribute to the nephropathy seen in these patients. New described genes causing immunodeficiency included caspase recruitment domain 11 (CARD11), mucosa-associated lymphoid tissue 1 (MALT1) for combined immunodeficiencies, and tetratricopeptide repeat domain 7A (TTC7A) for mutations associated with multiple atresia with combined immunodeficiency. Other observations expand the spectrum of clinical presentation of specific gene defects (eg, adult-onset idiopathic T-cell lymphopenia and early-onset autoimmunity might be due to hypomorphic mutations of the recombination-activating genes). Newborn screening in California established the incidence of severe combined immunodeficiency at 1 in 66,250 live births. The use of hematopoietic stem cell transplantation for PIDs was reviewed, with recommendations to give priority to research oriented to establish the best regimens to improve the safety and efficacy of bone marrow transplantation. These represent only a fraction of significant research done in patients with PIDs that has accelerated the quality of care of these patients. Genetic analysis of patients has demonstrated multiple phenotypic expressions of immune deficiency in patients with nearly identical genotypes, suggesting that additional genetic factors, possibly gene dosage, or environmental factors are responsible for this diversity.
 ...
PMID:Advances in basic and clinical immunology in 2013. 2458 42

Mastocytosis (M) is a clonal myeloid-disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a synthetic purine analog cytoreductive treatment, for which efficacy is mostly reported in advanced M. Here we report, with a long-term follow-up period (>10 years) efficacy and safety in 68 adult patients with M (36 [53%] had indolent M and 32 [47%] had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1-9). The overall response rate was 72% (complete remission [R]/major/partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (major/partial R: 56%/36%) and 50% (major/partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10 of 11 mediator release and 6 of 7 mast cell infiltration-related symptoms including urticaria pigmentosa and organomegaly (P < .02). Serum tryptase levels decreased (P = .01). Median durations of response were 3.71 (0.1-8) and 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies.
...
PMID:Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. 2629 17