Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives

Cudrici, Cornelia; Deuitch, Natalie; Aksentijevich, Ivona

doi:10.3390/ijms21093263

Cited by 75 publications

(67 citation statements)

References 95 publications

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“…The most demonstrative of these disorders in TNF receptor-associated periodic syndrome (TRAPS) resulting from autosomal dominant mutations in TNFSF1A . Although the exact mechanism is unclear, aberrant TNFR1 signaling, intracellular accumulation of misfolded proteins, and constitutive immune activation have been implicated in the pathogenesis ( 166 ). Patients most commonly experience severe abdominal pain, arthralgias, and myalgias ( 167 ).…”

Section: Monogenic Disorders Of Tnfr Signalingmentioning

confidence: 99%

Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

2020

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Since its discovery in 1975, TNFα has been a subject of intense study as it plays significant roles in both immunity and cancer. Such attention is well deserved as TNFα is unique in its engagement of pleiotropic signaling via its two receptors: TNFR1 and TNFR2. Extensive research has yielded mechanistic insights into how a single cytokine can provoke a disparate range of cellular responses, from proliferation and survival to apoptosis and necrosis. Understanding the intracellular signaling pathways induced by this single cytokine via its two receptors is key to further revelation of its exact functions in the many disease states and immune responses in which it plays a role. In this review, we describe the signaling complexes formed by TNFR1 and TNFR2 that lead to each potential cellular response, namely, canonical and non-canonical NF-κB activation, apoptosis and necrosis. This is followed by a discussion of data from in vivo mouse and human studies to examine the differential impacts of TNFR1 versus TNFR2 signaling.

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Section: Monogenic Disorders Of Tnfr Signalingmentioning

confidence: 99%

Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

2020

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“…Pathogenic missense mutations in the extracellular domain of TNFR1 (encoded by TNFRSF1A) causes TNF Receptor-associated Periodic Syndrome (TRAPS), an autosomal dominant autoinflammatory disease ( 64 ). The clinical manifestations of TRAPS include periodic long-lasting fever, serositis, abdominal pain, arthralgia, migratory skin rash, and myalgia ( 65 ). The molecular pathogenesis of TRAPS is still elusive, and the contribution of cell death pathways have not been investigated.…”

Section: The Role Of Ripk1 In Other Autoinflammatory and Autoimmune Disordersmentioning

confidence: 99%

RIPK1-Associated Inborn Errors of Innate Immunity

et al. 2021

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RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a key molecule for mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors (DRs) and pattern recognition receptors (PRRs). RIPK1 functions are regulated by multiple post-translational modifications (PTMs), including ubiquitination, phosphorylation, and the caspase-8-mediated cleavage. Dysregulation of these modifications leads to an immune deficiency or a hyperinflammatory disease in humans. Over the last decades, numerous studies on the RIPK1 function in model organisms have provided insights into the molecular mechanisms of RIPK1 role in the maintenance of immune homeostasis. However, the physiological role of RIPK1 in the regulation of cell survival and cell death signaling in humans remained elusive. Recently, RIPK1 loss-of-function (LoF) mutations and cleavage-deficient mutations have been identified in humans. This review discusses the molecular pathogenesis of RIPK1-deficiency and cleavage-resistant RIPK1 induced autoinflammatory (CRIA) disorders and summarizes the clinical manifestations of respective diseases to help with the identification of new patients.

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“…In the same way, the recent advances about the pivotal role of IL-1 in TRAPS pathogenesis as well as the excellent results observed in clinical trials have increasingly enhanced the use of IL-1 antagonists at the expense of the anti-TNF-α agents (11,(19)(20)(21)(22). On the other hand, etanercept represents the most widely employed anti-TNFα agent for TRAPS (1,6,23), as the monoclonal antibodies infliximab and adalimumab have been anecdotally associated to paradoxical inflammatory attacks in such patients (8,9,24). As also reported in the text, the number of patients discontinuing corticosteroids was statistically significant higher in adult-onset TRAPS patients when compared to pediatric-onset patients at 3-month (p = 0.01) and 6-month (p = 0.02) assessments.…”

Section: Discussionmentioning

confidence: 99%

Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome—Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network

et al. 2021

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Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001–0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301–0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed.Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.

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Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives

Cited by 75 publications

References 95 publications

Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

RIPK1-Associated Inborn Errors of Innate Immunity

Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome—Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network

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