XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease

Marsh, Rebecca; Madden, Lisa; Kitchen, Brenda J.; Mody, Rajen; McClimon, Brad; Jordan, Michael B.; Bleesing, Jack J.; Zhang, Kejian; Filipovich, Alexandra H.

doi:10.1182/blood-2010-01-256099

Cited by 236 publications

(275 citation statements)

References 26 publications

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“…Patients Pt8 and Pt9 were reported in a previous report as Patient 3 and Patient 9, respectively [5]. All patients showed typical features of HLH, such as persistent fever, cytopenia, liver dysfunction, and hyperferritinemia during the acute phase of HLH.…”

Section: Patientsmentioning

confidence: 84%

“…Flow cytometric and Western blot analysis of intracellular XIAP were performed, as described previously [5,14].…”

Section: Analysis Of Xiap Mutations and Protein Expressionmentioning

confidence: 99%

“…In contrast to SAP, XIAP is expressed ubiquitously. Patients with XIAP deficiency have been reported to develop HLH more frequently compared with SAP deficiency [5]. However, it remains unknown why a deficiency of XIAP leads to HLH and its recurrence in patients with XIAP deficiency.…”

Section: Introductionmentioning

confidence: 97%

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Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

et al. 2014

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X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency.3

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Section: Patientsmentioning

confidence: 84%

“…Flow cytometric and Western blot analysis of intracellular XIAP were performed, as described previously [5,14].…”

Section: Analysis Of Xiap Mutations and Protein Expressionmentioning

confidence: 99%

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Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

et al. 2014

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“…31 XLP2 is caused by mutations in BIRC4, which encodes XIAP, and has been described as an X-linked form of FHLH. 32 Recent observations suggest that lymphocytes from patients with both types of XLP demonstrate decreased activation-induced apoptosis that contributes to the uncontrolled lymphoproliferation. Taken all together, these genetic disorders still account for less than half of the diagnosed cases of HLH in children, including many familial cases still awaiting molecular definition.…”

Section: Genetic Factors For Mas In Sjiamentioning

confidence: 99%

Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment

et al. 2012

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Macrophage activation syndrome (MAS) is a severe, frequently fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis leading to coagulopathy, pancytopenia, and liver and central nervous system dysfunction. MAS is overt in 10% of children with sJIA but occurs subclinically in another 30 --40%. It is difficult to distinguish sJIA disease flare from MAS. Development of criteria for establishing MAS as part of sJIA are under way and will hopefully prove sensitive and specific. Mutations in cytolytic pathway genes are increasingly being recognized in children who develop MAS as part of sJIA. Identification of these mutations may someday assist in MAS diagnosis. Defects in cytolytic genes have provided murine models of MAS to study pathophysiology and treatment. Recently, the first mouse model of MAS not requiring infection but rather dependent on repeated stimulation through Toll-like receptors was reported. This provides a model of MAS that may more accurately reflect MAS pathology in the setting of autoinflammation or autoimmunity. This model confirms the importance of a balance between pro-and anti-inflammatory cytokines. There has been remarkable progress in the use of anti-pro-inflammatory cytokine therapy, particularly against interleukin-1, in the treatment of secondary forms of MAS, such as in sJIA.

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“…Recently, studies found that loss-of-function mutations in certain gene cause X linked lymphoproliferative disease [65,66]. By using interphase fluorescence in situ hybridization (FISH), Ansell and his colleagues found a novel translocation involving the IGH locus and an unknown partner in a primary MALT lymphoma patient with SS [67].…”

Section: T(x;14)(p11;q32)-igh-gpr34mentioning

confidence: 99%

Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue—from (auto)antigen driven selection to the activation of NF-κB signaling

Zhang

Wei

et al. 2015

Sci. China Life Sci.

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Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra-or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-B signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future. malt lymphoma, helicobacter pylori, chromosomal translocation, genetic alteration, NF-B Citation:Zhang YA, Wei Z, Li J, Liu P. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue-from (auto)antigen driven selection to the activation of NF-B signaling.

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XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease

Cited by 236 publications

References 26 publications

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment

Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue—from (auto)antigen driven selection to the activation of NF-κB signaling

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