Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature

Staels, Frederik; Betrains, Albrecht; Doubel, Peter; Willemsen, Mathijs; Cleemput, Vincent; Vanderschueren, Steven; Corveleyn, Anniek; Meyts, Isabelle; Sprangers, Ben; Crow, Yanick J.; Humblet-Baron, Stéphanie; Liston, Adrian; Schrijvers, R.

doi:10.3389/fimmu.2020.575219

Cited by 38 publications

(46 citation statements)

References 8 publications

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“…Finally, epistasis (dependency of the effect of a mutation on the presence or absence of mutations in the same or other genes) can affect disease presentation. In patients with STING associated vasculopathy with onset in infancy (SAVI), caused by GOF mutations in STING, disease-onset and manifestations can be influenced by single nucleotide polymorphisms (SNPs) in STING itself or in other IFN related genes such as IFIH1 ( 20 ).…”

Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

“…Knock in mice with a GOF mutation in STING (p.N153S) only developed pulmonary fibrosis after infection with gamma herpes virus 68 (γHV68), and this could be prevented by administration of cidofovir, an antiviral drug against γHV68 ( 23 ). It is unclear how these data translate to human patients, but adult-onset pulmonary fibrosis has been reported in SAVI ( 20 ). Infections can also trigger immune dysregulation, as observed in patients with familial hemophagocytic lymphohistiocytosis (fHLH), most commonly caused by mutations in PRF1 , where bouts of autoinflammation often coincide with upper respiratory or gastrointestinal infections ( 24 ).…”

Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

“…Recessive inheritance of GOF mutations has recently been described ( 167 ). Clinical manifestations mainly consist of pulmonary (interstitial lung disease, fibrosis), systemic (fever, failure to thrive) or skin manifestations (chilblains, digital ischemia) ( 163 ). Although the acronym suggests an infancy onset, adult-onset vasculitis with renal manifestations has been reported in a patient ( 163 ).…”

Section: Genetic Defects Associated With Adult-onset Ieimentioning

confidence: 99%

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Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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Inborn errors of immunity (IEI) are a heterogenous group of disorders driven by genetic defects that functionally impact the development and/or function of the innate and/or adaptive immune system. The majority of these disorders are thought to have polygenic background. However, the use of next-generation sequencing in patients with IEI has led to an increasing identification of monogenic causes, unravelling the exact pathophysiology of the disease and allowing the development of more targeted treatments. Monogenic IEI are not only seen in a pediatric population but also in adulthood, either due to the lack of awareness preventing childhood diagnosis or due to a delayed onset where (epi)genetic or environmental factors can play a role. In this review, we discuss the mechanisms accounting for adult-onset presentations and provide an overview of monogenic causes associated with adult-onset IEI.

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Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

Section: Genetic Defects Associated With Adult-onset Ieimentioning

confidence: 99%

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Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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“…SLE and other autoimmune diseases [76] ANCA-associated vasculitis [84] Herpes simplex virus infection [85] COPA syndrome αCOP Transport vesicles between Golgi to ER Infections and aberrant inflammatory responses:…”

Section: Nlrp12 Autoinflammatory Syndromementioning

confidence: 99%

Molecular biology of autoinflammatory diseases

et al. 2021

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The long battle between humans and various physical, chemical, and biological insults that cause cell injury (e.g., products of tissue damage, metabolites, and/or infections) have led to the evolution of various adaptive responses. These responses are triggered by recognition of damage-associated molecular patterns (DAMPs) and/or pathogen-associated molecular patterns (PAMPs), usually by cells of the innate immune system. DAMPs and PAMPs are recognized by pattern recognition receptors (PRRs) expressed by innate immune cells; this recognition triggers inflammation. Autoinflammatory diseases are strongly associated with dysregulation of PRR interactomes, which include inflammasomes, NF-κB-activating signalosomes, type I interferon-inducing signalosomes, and immuno-proteasome; disruptions of regulation of these interactomes leads to inflammasomopathies, relopathies, interferonopathies, and proteasome-associated autoinflammatory syndromes, respectively. In this review, we discuss the currently accepted molecular mechanisms underlying several autoinflammatory diseases.

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“…After the classification of AGS, other IFN-related disorders have been associated with brain involvement. Even if neurologic manifestations are not part of the typical clinical picture in the STING-associated vasculopathy with onset in infancy (SAVI), some cases have been reported with central nervous system (CNS) involvement [ 11 , 42 ]. Saldanha et al described a peculiar STING mutation resulting in an unusual SAVI phenotype without cutaneous vasculitis and increased systemic inflammation markers, but with the occurrence of opportunistic infection (potentially life-threatening) and a slow-improving developmental delay [ 43 ].…”

Section: From Monogenic To Multifactorial: Interferon-related Brain Disordersmentioning

confidence: 99%

Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain

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Mencaroni

et al. 2021

IJERPH

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More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology could be fostered by a better understanding of the disease machinery, to develop a rational use of immuno-modulators in clinical trials. In this review, we focus on monogenic disorders with neurological hyper-inflammation/autoimmunity as simplified “models” to correlate immune pathology and targeted treatments. The study of monogenic models yields great advantages for the elucidation of the pathogenic mechanisms that can be reproduced in cellular/animal models, overcoming the limitations of biological samples to study. Moreover, monogenic disorders provide a unique tool to study the mechanisms of neuroinflammatory and autoimmune brain damage, in all their manifestations. The insight of clinical, pathological, and therapeutic aspects of the considered monogenic models can impact knowledge about brain inflammation and can provide useful hints to better understand and cure some neurologic multifactorial disorders.

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Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature

Cited by 38 publications

References 8 publications

Monogenic Adult-Onset Inborn Errors of Immunity

Monogenic Adult-Onset Inborn Errors of Immunity

Molecular biology of autoinflammatory diseases

Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain

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