Autoinflammation with Infantile Enterocolitis Associated with Recurrent Perianal Abscesses

Siahanidou, Tania; Nikaina, Eirini; Kontogiorgou, Christina; Tzanoudaki, Marianna; Stefanaki, Kalliopi; Skiathitou, Anna-Venetia; Petropoulou, Theoni; Kanariou, Maria

doi:10.1007/s10875-019-00611-w

Cited by 6 publications

(14 citation statements)

References 7 publications

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“…However, most importantly, the cytotoxic cell function of AIFEC patients returned to normal level after the flare resolved, reflecting an intact granule-dependent cytotoxicity machinery of the cytotoxic cells. Extremely elevated serum IL-18 concentrations are another biomarker in AIFEC/NLRC4-MAS patients that could be used to distinguished them from primary HLH (12,13,18,21,(25)(26)(27). Gastrointestinal diseases such as diarrhea, bloody stool and recurrent perianal abscesses also help differentiate AIFEC from HLH (12,13,18,21,26,27).…”

Section: Discussionmentioning

confidence: 99%

“…Extremely elevated serum IL-18 concentrations are another biomarker in AIFEC/NLRC4-MAS patients that could be used to distinguished them from primary HLH ( 12 , 13 , 18 , 21 , 25 – 27 ). Gastrointestinal diseases such as diarrhea, bloody stool and recurrent perianal abscesses also help differentiate AIFEC from HLH ( 12 , 13 , 18 , 21 , 26 , 27 ). Among the 7 AIFEC patients, six of them had a mutation at the acid residue 341, which shows that valine 341 is a hot-spot mutation.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria

et al. 2021

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BackgroundNOD-like receptor family CARD-containing 4 protein (NLRC4) is a cytosolic protein that forms an inflammasome in response to flagellin and type 3 secretion system (T3SS) proteins from invading Gram-negative bacteria. NLRC4 mutations have been recently identified in early-onset severe autoinflammatory disorders. In this study, we reported a novel mutation in NLRC4 in two Chinese patients, who manifested with recurrent urticaria and arthralgia.MethodsWe summarized the clinical data of the two patients. Gene mutations were identified by whole-exome sequencing (WES). Swiss-PdbViewer was used to predict the pathogenicity of the identified mutations. Cytokine levels and caspase-1 activation were detected in the patient PBMCs with lipopolysaccharide (LPS) stimulation. All previously published cases with NLRC4 mutations were reviewed.ResultsWe identified a missense heterozygous mutation (c.514G>A, p.Gly172Ser), which was located in the highly conserved residue of nucleotide-binding domain (NBD) of NLRC4. The mutation did not alter the expression of NLRC4 protein, but induced considerably much higher production of IL-1β and IL-6 in patient PBMCs than in healthy controls after LPS stimulation. Four NLRC4 inflammasomopathy phenotypes have been described, with severe inflammatory diseases including macrophage activation syndrome, enterocolitis and NOMID in patients with mutations in the NBD and HD1 domains, whereas a mild clinical phenotype was associated with two mutations in the WHD domain of NLRC4.ConclusionWe identified a novel mutation in the NBD domain, and the patients just presented with a mild inflammatory phenotype. Thus, our findings reinforce the diversity of NLRC4 mutations and expand the clinical spectrum of associated diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria

et al. 2021

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“…NLRC4-MAS is a rare disease with less than 15 reported patients 54 55 58–62. The first signs and symptoms usually manifest in the neonatal period.…”

Section: The Nlrc4 Inflammasome-associated Autoinflammatory Diseasementioning

confidence: 99%

“…Clinically, it presents as recurrent bouts of fever, enterocolitis with loose stools up to bloody diarrhoea and vomiting, a wide range of different cutaneous manifestations, hepatosplenomegaly and lymphadenopathy. Flares can last up to several weeks and were reported to recur up to 11 times in 6 months 59 62. Disease episodes can be triggered by upper respiratory tract infections, minor surgery, physical stressors and emotional stress 54 59.…”

Section: The Nlrc4 Inflammasome-associated Autoinflammatory Diseasementioning

confidence: 99%

“…Flares can last up to several weeks and were reported to recur up to 11 times in 6 months 59 62. Disease episodes can be triggered by upper respiratory tract infections, minor surgery, physical stressors and emotional stress 54 59. If left untreated, life-threatening multiorgan failure including renal failure, respiratory distress syndrome and disseminated intravascular coagulopathy can occur 54 55.…”

Section: The Nlrc4 Inflammasome-associated Autoinflammatory Diseasementioning

confidence: 99%

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Cutaneous signs and mechanisms of inflammasomopathies

et al. 2022

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The emerging group of autoinflammatory diseases (AIDs) is caused by a dysregulation of the innate immune system while lacking the typical footprint of adaptive immunity. A prominent subgroup of AIDs are inflammasomopathies, which are characterised by periodic flares of cutaneous signs as well as systemic organ involvement and fever. The range of possible skin lesions is vast, ranging from urticarial, erysipelas-like and pustular rashes to erythematous patches, violaceous plaques and eventual necrosis and ulceration. This review provides a structured overview of the pathogenesis and the clinical picture with a focus on dermatological aspects of inflammasomopathies. Current treatment options for these conditions are also discussed.

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NLRC4-Related Autoinflammatory Syndrome with Macrophage Activation Syndrome

Rayzan

Rezaei

2021

Genetic Syndromes

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Autoinflammation with Infantile Enterocolitis Associated with Recurrent Perianal Abscesses

Cited by 6 publications

References 7 publications

A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria

A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria

Cutaneous signs and mechanisms of inflammasomopathies

NLRC4-Related Autoinflammatory Syndrome with Macrophage Activation Syndrome

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