Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet’s syndrome patients

Yüksel, Şahru; Eren, Elif; Hatemi, Gülen; Sahillioğlu, Ali Can; Gültekin, Yetiş; Demiröz, Duygu; Akdiş, Cezmi A.; Fresko, İzzet; Özören, Nesrin

doi:10.1093/intimm/dxt046

Cited by 35 publications

(22 citation statements)

References 15 publications

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“…[5] TNF-α production is elevated in the intestinal tissues of intestinal BD patients [6] and in peripheral blood cells of VBD patients, [7] while IL-6 concentrations are elevated in the cerebrospinal fluid (CSF) of NBD patients. [8] …”

Section: Introductionmentioning

confidence: 99%

Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease

et al. 2016

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Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy.IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint).The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3 intestinal BD patients, resulting in the improvement of clinical symptoms, CRP levels, and visual analogue scale score. Safety and pharmacokinetics profiles were comparable to those in patients with rheumatoid arthritis or Crohn disease. These findings support IFX as a new therapeutic option for patients with intestinal BD, NBD, or VBD.

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Section: Introductionmentioning

confidence: 99%

Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease

et al. 2016

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“…64 Four mutations of the NLRP3/cryopyrin gene were identified in a study conducted with 50 cases of BD. 65 However, another study was unable to demonstrate a greater activation of caspase-1 through the inflammasome pathway in dendritic cells and neutrophils of sick patients, as compared to the controls. 66 …”

Section: Dermatological Diseases Associated With Inflammasomesmentioning

confidence: 94%

Inflammasomes and dermatology

Sá

Neto

2016

An. Bras. Dermatol.

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Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.

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“…Some authors suggest a link between NLRP3 activation and Alzheimer disease [79,80], or Behçet disease [81].…”

Section: Nlrp3 In Other Multifactorial Diseasesmentioning

confidence: 99%

Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

Sarrabay¹,

Grandemange

Touitou

2015

Expert Review of Clinical Immunology

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Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.

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Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet’s syndrome patients

Cited by 35 publications

References 15 publications

Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease

Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease

Inflammasomes and dermatology

Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

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