7 research outputs found
ΠΠ²ΡΠΎΠΏΠ΅ΠΈΠ·ΠΌΡ ΠΊΠ°ΠΊ ΡΠ΅ΡΠΌΠΈΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π½ΠΎΠΌΠΈΠ½Π°ΡΠΈΠ²Π½ΡΠ΅ Π΅Π΄ΠΈΠ½ΠΈΡΡ Π² ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ΅ΡΠΌΠΈΠ½ΠΎΡΠΈΡΡΠ΅ΠΌ ΡΠ°ΡΠ°ΡΡΠΊΠΎΠΉ ΡΡΠΈΠ΄ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠΌΠΈΠ½ΠΎΠ»ΠΎΠ³ΠΈΠΈ
Π¦Π΅Π»Ρ ΡΡΠ°ΡΡΠΈ: Π²ΡΡΠ²ΠΈΡΡ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ Π°Π΄Π°ΠΏΡΠ°ΡΠΈΠΈ ΡΠ΅ΡΠΌΠΈΠ½ΠΎΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ²-Π΅Π²ΡΠΎΠΏΠ΅ΠΈΠ·ΠΌΠΎΠ² (ΡΠ»ΠΎΠ²Π° Π·Π°ΠΏΠ°Π΄Π½ΠΎ-Π΅Π²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΈΡ
ΡΠ·ΡΠΊΠΎΠ² Π² ΡΠΎΡΡΠ°Π²Π΅ ΡΠ°ΡΠ°ΡΡΠΊΠΎΠ³ΠΎ ΡΠ·ΡΠΊΠ°)
Case Report A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections
We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency disorders (CVIDs). Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu), which is found also in healthy controls
Hairy Cell Leukemia-Specific Recognition by Multiple Autologous HLA-DQ or DP-Restricted T-Cell Clones
A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach β₯5 positive criteria out of the 8 HLH-2004 criteria can be time consuming and may delay timely initiation of treatment. Hence, we applied a data-driven approach to identify a minimal parameter set for early decision-making towards the initiation of HLH-specific treatment. We retrospectively evaluated 165 patients from five Dutch tertiary hospitals with suspected HLH. Sixteen pHLH (median age 0.5Β years) and 70 sHLH patients (median age 8.7Β years) were identified using the HLH-2004 criteria. Clustering analysis and multi-receiver operator characteristics were used to identify parameters distinctive of HLH. The presence of either increased ferritin, cytopenia in β₯2 lineages, or splenomegaly distinguished HLH from non-HLH cases with a negative predictive value of 100%. A minimal parameter set consisting of 2 major criteria (phagocytosis and splenomegaly) and 3 minor criteria (cytopenia, increased ferritin, and increased triglycerides/low fibrinogen) predicted HLH with 95% (88β99) sensitivity and 94% (86β98) specificity. This finding was replicated in an independent retrospective validation cohort of 109 US patients (n = 109). By dividing a subset of the HLH-2004 criteria into major and minor criteria, this strategy uses the evaluation of less than 5 criteria to quickly identify patients with HLH. When confirmed in a prospective setting, this approach could be of value for timely diagnosis and treatment of HLH.</p
Targeted next-generation sequencing: a novel diagnostic tool for primary immunodeficiencies
BACKGROUND: Primary immunodeficiency (PID) disorders are a heterogeneous group of inherited disorders caused by a variety of monogenetic immune defects. Thus far, mutations in more than 170 different genes causing PIDs have been described. A clear genotype-phenotype correlation is often not available, which makes a genetic diagnosis in patients with PIDs complex and laborious. OBJECTIVE: We sought to develop a robust, time-effective, and cost-effective diagnostic method to facilitate a genetic diagnosis in any of 170 known PID-related genes by using next-generation sequencing (NGS). METHODS: We used both targeted array-based and in-solution enrichment combined with a SOLiD sequencing platform and a bioinformatic pipeline developed in house to analyze genetic changes in the DNA of 41 patients with PIDs with known mutations and 26 patients with undiagnosed PIDs. RESULTS: This novel NGS-based method accurately detected point mutations (sensitivity and specificity >99% in covered regions) and exonic deletions (100% sensitivity and specificity). For the 170 genes of interest, the DNA coverage was greater than 20Γ in 90% to 95%. Nine PID-related genes proved not eligible for evaluation by using this NGS-based method because of inadequate coverage. The NGS method allowed us to make a genetic diagnosis in 4 of 26 patients who lacked a genetic diagnosis despite routine functional and genetic testing. Three of these patients proved to have an atypical presentation of previously described PIDs. CONCLUSION: This novel NGS tool facilitates accurate simultaneous detection of mutations in 161 of 170 known PID-related genes. In addition, these analyses will generate more insight into genotype-phenotype correlations for the different PID disorders
Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations
Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation syndrome. STXBP2, also known as MUNC18-2, has recently been identified as the disease-causing gene in FHL type 5 (FHL-5). A role for STXBP2 in neutrophils, and for neutrophils in FHL in general, has not been documented thus far. Here, we report that FHL-5 neutrophils have a profound defect in granule mobilization, resulting in inadequate bacterial killing, in particular, of gram-negative Escherichia coli, but not of Staphylococcus aureus, which rather depends on intact reduced NAD phosphate oxidase activity. This impairment of bacterial killing may contribute to the apparent susceptibility to gastrointestinal tract inflammation in patients with FHL-