A multidisciplinary non-invasive approach to monitor response to intravenous immunoglobulin treatment in neurodegenerative Langerhans cell histiocytosis: a real-world study.

Aims: Early detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients.

Methods: Patients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.

Outcome of primary hemophagocytic lymphohistiocytosis: a report on 143 patients from the Italian Registry.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (interquartile range, 2-81), and 92 patients (64%) fulfilled the HLH-2004 criteria.

Childhood-onset Erdheim-Chester disease in the molecular era: clinical phenotypes and long-term outcomes of 21 patients.

Erdheim-Chester disease (ECD) is a rare histiocytic disorder that can present as a localized infiltration of foamy histiocytes or a multisystem disease that may be life-threatening. It is extremely rare in children. Pegoraro and colleagues present the clinical and molecular features of 21 patients with pediatric ECD through a large international collaboration, documenting that it resembles its adult counterpart, with similar molecular features and responses to agents targeting BRAF and MEK.

Approaching hemophagocytic lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical condition characterized by sustained but ineffective immune system activation, leading to severe and systemic hyperinflammation. It may occur as a genetic or sporadic condition, often triggered by an infection. The multifaceted pathogenesis results in a wide range of non-specific signs and symptoms, hampering early recognition.

STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients.

Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.

Inborn errors of immunity (IEI) are genetic disorders characterized by a wide spectrum of clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation. Among these, primary immune regulatory disorders (PIRDs) are mainly presenting with autoimmune manifestations, and autoimmune cytopenias (AICs) can be the first clinical sign. Significantly, AICs in patients with IEI often fail to respond to first-line therapy.

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.

gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke.

Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review.

Background: Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings.

Methods: The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement.

Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding.

Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare and often fatal disorder characterized by defective cellular cytotoxicity and hyperinflammation, and the only cure known to date is hematopoietic stem cell transplantation. Mutations in RAB27A, LYST, and AP3B1 give rise to FHL associated with oculocutaneous albinism, and patients with FHL are usually only screened for mutations in these genes when albinism is observed. A number of patients with FHL and normal pigmentation remain without a genetic diagnosis.

Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning.

The human immune system depends on the activity of cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of familial hemophagocytic lymphohistiocytosis (FHL). Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL.

14q32/miRNA clusters loss of heterozygosity in acute lymphoblastic leukemia is associated with up-regulation of BCL11a.

This study evaluated the loss and expression level of miRNAs 14q32 clusters in acute lymphoblastic leukemia (ALL) patients with cryptic deletions at 14q32 chromosomal band to investigate their involvement in this disease. We demonstrate that a subset of ALL cases bearing 14q32 LOH showed a down-regulation of miRNA 14q32 clusters, which is directly linked to the submicroscopic chromosomal deletion. As a consequence of miRNAs deregulation we reported an inverse correlation with the expression of their target BCL11a, a transcription factor involved in lymphoid differentiation.