Two new families with X-linked inhibitor of apoptosis deficiency and a review of all 26 published cases

Horn, Peter; Belohradsky, Bernd H.; Urban, Christian; Weber-Mzell, Daniela; Meindl, Alfons; Schuster, Volker

doi:10.1016/j.jaci.2010.11.040

Cited by 17 publications

(12 citation statements)

References 6 publications

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“…Worldwide, more than 70 XIAP-deficient patients have been reported in the literature [9,11,8,7,[26][27][28][29]. Over the last few years, we have identified additional patients and have been made aware of yet other patients by our collaborators (Aguilar and Latour, unpublished observations).…”

Section: Clinical Featuresmentioning

confidence: 94%

X-linked Inhibitor of Apoptosis Protein Deficiency: More than an X-linked Lymphoproliferative Syndrome

2015

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X-linked inhibitor of apoptosis (XIAP) deficiency (also known as X-linked lymphoproliferative syndrome type 2, XLP-2) is a rare primary immunodeficiency. Since the disease was first described in 2006, more than 70 patients suffering from XIAP-deficiency have been reported, thus extending the clinical presentations of the disease. The main clinical features of XLP-2 are (i) elevated susceptibility to hemophagocytic lymphohistiocytosis (HLH, frequently in response to infection with Epstein-Barr virus (EBV)), (ii) recurrent splenomegaly and (iii) inflammatory bowel disease (IBD) with the characteristics of Crohn's disease. XIAP deficiency is now considered to be one of the genetic causes of IBD in infancy. Although XIAP is an anti-apoptotic molecule, it is also involved in many other pathways, including the regulation of innate immunity and inflammation. XIAP is required for signaling through the Nod-like receptors NOD1 and 2, which are intracellular sensors of bacterial infection. XIAP-deficient T cells (including innate natural killer T cells and mucosal-associated invariant T cells) are overly sensitive to apoptosis. NOD2 function is impaired in XIAP-deficient monocytes. However, the physiopathological mechanisms underlying the clinical phenotypes in XIAP deficiency, notably the HLH and the EBV susceptibility, are not well understood. Here, we review the clinical aspects, molecular etiology and physiopathology of XIAP deficiency.

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Section: Clinical Featuresmentioning

confidence: 94%

X-linked Inhibitor of Apoptosis Protein Deficiency: More than an X-linked Lymphoproliferative Syndrome

2015

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“…There may be a diagnostic dilemma if the GI symptoms are the first or only manifestation of PID. Patients may be diagnosed and treated as CD or UC before the diagnosis of a PID has been entertained or demonstrated (100,101). In these patients, IBD treatment options may be inappropriate or even harmful.…”

Section: Pidsmentioning

confidence: 99%

“…In these patients, IBD treatment options may be inappropriate or even harmful. Monogenetic immune disorders involving the interleukin-10 axis or XIAP gene presenting with intestinal or perianal disease can be proven or disproven by genetic or functional testing (101)(102)(103). A high degree of suspicion for PID is required in infantile-onset IBD or if the history shows any of the alarm symptoms or signs listed in Table 4 because PIDs may manifest as IBD during childhood.…”

Section: Pidsmentioning

confidence: 99%

ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents

Levine

Koletzko

Turner

et al. 2014

J. pediatr. gastroenterol. nutr.

1,092

787

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Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while

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“…These mutations include missense and nonsense mutations, small/large deletions and small insertions leading either to aberrant protein function or decreased/absent protein expression. The most common clinical manifestations of XIAP deficiency include recurrent/persistent splenomegaly, hemophagocytic lymphohistiocytosis syndrome, which can be initiated by EBV infection, and hypogammaglobulinemia 68 , 69 , 70 . Yet, XIAP deficiency has more often been linked to inflammatory bowel disease with clinical and histological features of Crohn's disease or a mixed XLP‐2/inflammatory bowel disease phenotype 70 , 71 , 72 , 73 …”

Section: Perspective On Iap Functionmentioning

confidence: 99%

Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins

et al. 2017

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Understanding how inhibitor of apoptosis proteins (IAPs) regulate apoptosis and necroptosis has been fast-forwarded by the use of Smac mimetics (SMs) to deplete or inhibit the IAPs, specifically cIAP1, cIAP2 and XIAP. The loss or inhibition of cIAP1, cIAP2 and XIAP causes the majority of cells to be sensitized to death receptor induced cell death, such as with tumour necrosis factor (TNF). Mouse genetics shows that there is some functional redundancy and the use of SMs has allowed us to understand how changing the composition of proteins recruited to TNF receptor 1 on TNF ligation can alter protein complex formation and activation of apoptosis or necroptosis, particularly when caspases are inhibited. Determining when or how caspase inhibition occurs physiologically combined with the loss of IAPs will be the next challenge in understanding the ability of IAPs to prevent cell death and/or limit inflammation.

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Two new families with X-linked inhibitor of apoptosis deficiency and a review of all 26 published cases

Cited by 17 publications

References 6 publications

X-linked Inhibitor of Apoptosis Protein Deficiency: More than an X-linked Lymphoproliferative Syndrome

X-linked Inhibitor of Apoptosis Protein Deficiency: More than an X-linked Lymphoproliferative Syndrome

ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents

Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins

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