{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSAP, the protein product of SH2D1A, is a small adaptor molecule uniquely composed of a single SH2 domain that plays an essential role in lymphocyte signaling. Expressed predominantly in T cells, natural killer (NK) cells, and innate‐like NKT cells, SAP modulates signal transduction downstream of the SLAM (signaling lymphocyte activation molecule) family receptors. Structural and biochemical studies have revealed that SAP binds both phosphotyrosine‐containing motifs and the SH3 domain of Src family kinases (notably FynT) through a non‐classical interaction mode. This dual binding capacity not only promotes the recruitment and activation of kinases but also competitively blocks the association of inhibitory phosphatases, thus fine‐tuning immune cell activation. Notably, SAP is indispensable for NKT cell development and for appropriate cytokine responses, with its absence underpinning the pathogenesis of X‐linked lymphoproliferative disease (XLP)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond early receptor signaling, SAP is vital for effector functions of cytotoxic lymphocytes. It orchestrates the polarization and assembly of the cytolytic machinery in cytotoxic T lymphocytes (CTLs) and NK cells—processes that are particularly critical for the immune response against Epstein–Barr virus (EBV). By mediating signals via receptors such as 2B4 and NTB-A, SAP ensures efficient lytic granule polarization, interferon‐γ production, and even the appropriate execution of restimulation‐induced cell death, all of which safeguard against uncontrolled lymphocyte expansion. In addition, SAP is required for establishing T cell help that underlies germinal center formation and long‐term humoral immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSAP itself is subject to dynamic regulation and interconnects broader signaling networks that govern lymphocyte homeostasis. Its expression is modulated by cytokines such as interleukin‐2 and by tumor suppressive pathways (for instance, via p53), linking SAP levels to cell cycle control and programmed cell death. Defective or mutated SH2D1A not only disrupts cytotoxic and T–B cell interactions—leading to impaired germinal center responses and altered naive B cell survival—but also precipitates immune dysregulation that manifests as susceptibility to viral infections (especially EBV), hypogammaglobulinemia, and in rare instances, vasculitis. These insights underscore SAP’s pivotal role as an integrator of activating and inhibitory signals in both innate and adaptive immunity and highlight its significance as a therapeutic target in XLP and related immunopathologic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Morra, M Simarro-Grande, M Martin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M101305200"}], "href": "https://doi.org/10.1074/jbc.M101305200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11477068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11477068"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Janos Sumegi, Thomas A Seemayer, Dali Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A spectrum of mutations in SH2D1A that causes X-linked lymphoproliferative disease and other Epstein-Barr virus-associated illnesses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Lymphoma (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10428190290026240"}], "href": "https://doi.org/10.1080/10428190290026240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12152986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12152986"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chengjun Li, Cristiana Iosef, Christina Y H Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206649200"}], "href": "https://doi.org/10.1074/jbc.M206649200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12458214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12458214"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Betty Chan, Arpad Lanyi, Hyun Kyu Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP couples Fyn to SLAM immune receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb920"}], "href": "https://doi.org/10.1038/ncb920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12545174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12545174"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pablo Engel, Michael J Eck, Cox Terhorst "}, {"type": "b", "children": [{"type": "t", "text": "The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nri1202"}], "href": "https://doi.org/10.1038/nri1202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14523387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14523387"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kim E Nichols, Jamie Hom, Shun-You Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of NKT cell development by SAP, the protein defective in XLP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1189"}], "href": "https://doi.org/10.1038/nm1189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15711562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15711562"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Benoit Pasquier, Luo Yin, Marie-Claude Fondanèche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20042432"}], "href": "https://doi.org/10.1084/jem.20042432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15738056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15738056"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Huai-Chia Chuang, Jong-Ding Lay, Wen-Chuan Hsieh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-04-1406"}], "href": "https://doi.org/10.1182/blood-2005-04-1406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16002423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16002423"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Reza Sharifi, Joanna C Sinclair, Kimberly C Gilmour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP mediates specific cytotoxic T-cell functions in X-linked lymphoproliferative disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-09-3359"}], "href": "https://doi.org/10.1182/blood-2003-09-3359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14726378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14726378"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hilary Williams, Karen Macsween, Karen McAulay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of immune activation and clinical events in acute infectious mononucleosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/421276"}], "href": "https://doi.org/10.1086/421276"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15195244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15195244"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Svitlana V Mikhalap, Larysa M Shlapatska, Olga V Yurchenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The adaptor protein SH2D1A regulates signaling through CD150 (SLAM) in B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-04-1273"}], "href": "https://doi.org/10.1182/blood-2004-04-1273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15315965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15315965"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Pedro Roda-Navarro, María Mittelbrunn, Mara Ortega, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic redistribution of the activating 2B4/SAP complex at the cytotoxic NK cell immune synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.173.6.3640"}], "href": "https://doi.org/10.4049/jimmunol.173.6.3640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15356108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15356108"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "N Nagy, M Takahara, J Nishikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wild-type p53 activates SAP expression in lymphoid cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207908"}], "href": "https://doi.org/10.1038/sj.onc.1207908"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15378026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15378026"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Stefan Mehrle, Susanne Frank, Jan Schmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP and SLAM expression in anti-CD3 activated lymphocytes correlates with cytotoxic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1711.2004.01302.x"}], "href": "https://doi.org/10.1111/j.1440-1711.2004.01302.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15661039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15661039"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Loïc Dupré, Grazia Andolfi, Stuart G Tangye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-08-3269"}], "href": "https://doi.org/10.1182/blood-2004-08-3269"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15677558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15677558"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Cuiping Gu, Stuart G Tangye, Xiaoqing Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The X-linked lymphoproliferative disease gene product SAP associates with PAK-interacting exchange factor and participates in T cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0606624103"}], "href": "https://doi.org/10.1073/pnas.0606624103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16983070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16983070"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Johanna Endt, Philipp Eissmann, Sabrina C Hoffmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of 2B4 (CD244) activity and regulated SAP expression in human NK cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200636341"}], "href": "https://doi.org/10.1002/eji.200636341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17171759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17171759"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "André Veillette, Shaohua Zhang, Xiaochu Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP expression in T cells, not in B cells, is required for humoral immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0710698105"}], "href": "https://doi.org/10.1073/pnas.0710698105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212118"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Chengjun Li, David Schibli, Shawn Shun-Cheng Li "}, {"type": "b", "children": [{"type": "t", "text": "The XLP syndrome protein SAP interacts with SH3 proteins to regulate T cell signaling and proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2008.09.014"}], "href": "https://doi.org/10.1016/j.cellsig.2008.09.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18951976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18951976"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Pamela L Schwartzberg, Kristen L Mueller, Hai Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLAM receptors and SAP influence lymphocyte interactions, development and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nri2456"}], "href": "https://doi.org/10.1038/nri2456"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19079134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19079134"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Noémi Nagy, Liudmila Matskova, Loránd L Kis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The proapoptotic function of SAP provides a clue to the clinical picture of X-linked lymphoproliferative disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0905691106"}], "href": "https://doi.org/10.1073/pnas.0905691106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19570996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19570996"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Andrew L Snow, Rebecca A Marsh, Scott M Krummey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI39518"}], "href": "https://doi.org/10.1172/JCI39518"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19759517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19759517"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Claire Booth, Kimberly C Gilmour, Paul Veys, et al. "}, {"type": "b", "children": [{"type": "t", "text": "X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-06-284935"}], "href": "https://doi.org/10.1182/blood-2010-06-284935"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20926771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20926771"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jana Pachlopnik Schmid, Danielle Canioni, Despina Moshous, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-07-298372"}], "href": "https://doi.org/10.1182/blood-2010-07-298372"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21119115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21119115"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Cheng Sun, Binqing Fu, Yufeng Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1002594"}], "href": "https://doi.org/10.1371/journal.ppat.1002594"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22438812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22438812"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Laurence Menard, Tineke Cantaert, Nicolas Chamberlain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling lymphocytic activation molecule (SLAM)/SLAM-associated protein pathway regulates human B-cell tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2013.10.051"}], "href": "https://doi.org/10.1016/j.jaci.2013.10.051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24373350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24373350"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Raffaella Meazza, Claudia Tuberosa, Valentina Cetica, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diagnosing XLP1 in patients with hemophagocytic lymphohistiocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2014.04.043"}], "href": "https://doi.org/10.1016/j.jaci.2014.04.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24985396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24985396"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ning Wu, Ming-Chao Zhong, Romain Roncagalli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A hematopoietic cell-driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3369"}], "href": "https://doi.org/10.1038/ni.3369"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26878112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26878112"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Lihi Radomir, Sivan Cohen, Matthias P Kramer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell-Cell Contact Mediated through SLAMF6 and SAP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1700557"}], "href": "https://doi.org/10.4049/jimmunol.1700557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28904129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28904129"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Paul E Gray, Tracey A O'Brien, Mayura Wagle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-015-0194-9"}], "href": "https://doi.org/10.1007/s10875-015-0194-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26433589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26433589"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Lucero Valenzuela-Vazquez, Juan Carlos Núñez-Enríquez, Jacqueline Sánchez-Herrera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0227314"}], "href": "https://doi.org/10.1371/journal.pone.0227314"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31951638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31951638"}]}]}]}