ArticleThe Journal of allergy and clinical immunology2014
Diagnosing XLP1 in patients with hemophagocytic lymphohistiocytosis.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- The neurologic face of X-linked lymphoproliferative syndrome type 1: a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- X-linked lymphoproliferative disease type 1: a clinical and genetic update.Frontiers in immunology · 2025Review
- Highly sensitive detection of Epstein-Barr virus-infected cells by EBER flow FISH.International journal of hematology · 2024Article
- Case report: Non-EBV associated cerebral vasculitis and cerebral hemorrhage in X-linked lymphoproliferative disease.Frontiers in immunology · 2024Article
- Immunology of Cytokine Storm Syndromes: Natural Killer Cells.Advances in experimental medicine and biology · 2024Review
- Approaching hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.Frontiers in immunology · 2023Review
- X-linked lymphoproliferative syndrome in mainland China: review of clinical, genetic, and immunological characteristic.European journal of pediatrics · 2020Article
- The Natural History of X-Linked Lymphoproliferative Disease (XLP1): Lessons from a Long-Term Survivor.Case reports in immunology · 2020Article
- Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.Frontiers in immunology · 2020Review
- Current Flow Cytometric Assays for the Screening and Diagnosis of Primary HLH.Frontiers in immunology · 2019Review
- Comparison of Th1/Th2 cytokine profiles between primary and secondary haemophagocytic lymphohistiocytosis.Italian journal of pediatrics · 2016Article
- Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.The Journal of allergy and clinical immunology · 2016Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundHemophagocytic lymphohistiocytosis (HLH) is a life-threatening, heterogeneous, hyperinflammmatory disorder. Prompt identification of inherited forms resulting from mutation in genes involved in cellular cytotoxicity can be crucial. X-linked lymphoproliferative disease 1 (XLP1), due to mutations in SH2D1A (Xq25) encoding signaling lymphocyte activation molecule-associated protein (SAP), may present with HLH. Defective SAP induces paradoxical inhibitory function of the 2B4 coreceptor and impaired natural killer (NK) (and T) cell response against EBV-infected cells.
objectiveTo characterize a cohort of patients with HLH and XLP1 for SAP expression and 2B4 function in lymphocytes, proposing a rapid diagnostic screening to direct mutation analysis.
methodsWe set up rapid assays for 2B4 function (degranulation or (51)Cr-release) to be combined with intracellular SAP expression in peripheral blood NK cells. We studied 12 patients with confirmed mutation in SH2D1A and some family members.
resultsThe combined phenotypic/functional assays allowed efficient and complete diagnostic evaluation of all patients with XLP1, thus directing mutation analysis and treatment. Nine cases were SAP(-), 2 expressed SAP with mean relative fluorescence intensity values below the range of healthy controls (SAP(dull)), and 1, carrying the R55L mutation, was SAP(+). NK cells from all patients showed inhibitory 2B4 function and defective killing of B-EBV cells. Carriers with SH2D1A mutations abolishing SAP expression and low percentage of SAP(+) cells showed neutral 2B4 function at the polyclonal NK cell level. Three novel SH2D1A mutations have been identified.
conclusionsStudy of SAP expression is specific but may have insufficient sensitivity for screening XLP1 as a single tool. Combination with 2B4 functional assay allows identification of all cases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.