scholarly journals COVID-19 infection in a patient with a systemic autoinflammatory syndrome due to an NLRC4 inflammasomopathy

2021 ◽  
Author(s):  
Jeffrey K Duncan-Lowey ◽  
Vaidehi Chowdhary ◽  
Dana W Dunne
Keyword(s):  
Autoinflammatory Diseases ◽  
Autoinflammatory Syndrome ◽  
Inflammasome Component

Abstract The effect of autoinflammatory diseases on SARS-CoV-2 infection remains unknown. We report a case of COVID-19 in a patient with autoinflammation with infantile enterocolitis (AIFEC) with inflammatory flares due to a mutation in the inflammasome component NLRC4. This case highlights the role of immunosuppression in patients with autoinflammation with COVID-19.

scholarly journals AB1010 CLINICAL SPECTRUM AND IMMUNE ANALYSIS OF PATIENTS WITH CRYOPYRIN-ASSOCIATED AUTOINFLAMMATORY SYNDROME IN TAIWAN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1798.1-1798
Author(s):  
C. Y. Wu ◽  
P. S. Chu ◽  
H. Y. Yang
Keyword(s):  
Genetic Variants ◽  
Medical Center ◽  
Laboratory Data ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Medical Intervention ◽  
Stimulation Test ◽  
Autoinflammatory Diseases ◽  
Missense Mutations ◽  
Autoinflammatory Syndrome ◽  
Nlrp3 Gene

Background:Cryopyrin-associated periodic syndromes (CAPS) are emerging autoinflammatory diseases with available treatment. No reports have yet been reported from Taiwan.Objectives:We reviewed cases suspected with CAPS to identify its existence in Taiwan.Methods:Genomic DNA from one hundred and ten cases with symptom signs suggestive of CAPS(1) between 2016-2019 were sent for NLRP3 gene analysis. Clinical presentations, laboratory data, treatment regimens, as well as inflammasome activities were analyzed among those treated in a tertiary medical center in northern Taiwan.Results:Among the 110 cases sequenced, 16 of them were found to carry missense mutations within the NLRP3 gene. Fourteen cases harbored known pathogenic genetic variants (c.1316C>T; c.1574A>T; and c.907G>C) and two carried novel NLRP3 missense mutations (c.210G>A, c.1371G>T)(2) with unknown pathophysiological roles. Through chart review, chronic urticarial, systemic juvenile idiopathic arthritis, Behcet’s disease and refractory Kawasaki disease were most likely diagnosed before genetic analysis were arranged. As compared to chronic infantile neurological, cutaneous and articular syndrome (CINCA) and Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) was the most frequently observed clinical presentation. Plasma serumamyloidA (SAA) and IL-1b were both significantly elevated among the cases diagnosed with CAPS as compared to the controls (p<0.05). IL-18, on the other hand, showed no significant differences between the groups. While the presence of LPS without ATP significantly increased the level of IL-1b in the PBMC stimulation test, IL-18 were significantly elevated in the confirmed CAPS with or without ATP upon LPS stimulation (all p<0.05). Caspase 1 activity were also tested positive among the cases with CAPS. Furthermore, we compared the immune profiles between those CAPS cases harboring pathogenic mutations with the 2 harboring unreported NLRP3 missense mutations and discovered that the PBMC stimulation test in cases with c.210G>A and c.1371G>T mutation did not differ from the healthy controls.Conclusion:The number of NLRP3 gene alterations among patients suspected with CAPS in Taiwan is not low. In order to identify potential patients for proper medical intervention in the future, physician awareness, genetic testing as well as functional analysis are important.References:[1]Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942-7.[2]Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018;55(8):530-7Disclosure of Interests:Chao-Yi Wu Speakers bureau: Abbvie, Boehringer Ingelheim International GmbH, Nestle, Pi-Shuang Chu: None declared, Huang-Yu Yang: None declared

scholarly journals The Role of Cutaneous Type I IFNs in Autoimmune and Autoinflammatory Diseases

2020 ◽  
Vol 205 (11) ◽  
pp. 2941-2950
Author(s):  
Jessica L. Turnier ◽  
J. Michelle Kahlenberg
Keyword(s):  
Autoinflammatory Diseases ◽  
Type I ◽  
Type I Ifns

scholarly journals PYPAF1 nonsense mutation in a patient with an unusual autoinflammatory syndrome: Role of PYPAF1 in inflammation

2006 ◽  
Vol 54 (2) ◽  
pp. 508-514 ◽  
Author(s):  
I. Jéru ◽  
H. Hayrapetyan ◽  
P. Duquesnoy ◽  
T. Sarkisian ◽  
S. Amselem
Keyword(s):  
Nonsense Mutation ◽  
Autoinflammatory Syndrome

scholarly journals S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β

2017 ◽  
Vol 214 (9) ◽  
pp. 2695-2713 ◽  
Author(s):  
Benjamin Weichand ◽  
Rüdiger Popp ◽  
Sarah Dziumbla ◽  
Javier Mora ◽  
Elisabeth Strack ◽  
...  
Keyword(s):  
Inflammasome Activation ◽  
Invasion And Metastasis ◽  
Tumor Associated Macrophages ◽  
Tumor Lymphangiogenesis ◽  
Inflammasome Component ◽  
S1p Receptor ◽  
Genetic Deletion ◽  
Nlrp3 Expression

Metastasis is the primary cause of cancer death. The inflammatory tumor microenvironment contributes to metastasis, for instance, by recruiting blood and lymph vessels. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1) alone in CD11bhi CD206+ TAMs infiltrating mouse breast tumors prevents pulmonary metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also observed in the nonrelated methylcholanthrene-induced fibrosarcoma model. Transcriptome analysis of isolated TAMs from both entities revealed reduced expression of the inflammasome component Nlrp3 in S1PR1-deficient TAMs. Macrophage-dependent lymphangiogenesis in vitro was triggered upon inflammasome activation and required both S1PR1 signaling and IL-1β production. Finally, NLRP3 expression in tumor-infiltrating macrophages correlated with survival, lymph node invasion, and metastasis of mammary carcinoma patients. Conceptually, our study indicates an unappreciated role of the NLRP3 inflammasome in promoting metastasis via the lymphatics downstream of S1PR1 signaling in macrophages.

scholarly journals Contrasting role of NLRP12 in autoinflammation: evidence from a case report and mouse models

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001824
Author(s):  
Dan Lévy ◽  
Alexandre Mariotte ◽  
Aurore DeCauwer ◽  
Cecile Macquin ◽  
Angélique Pichot ◽  
...  
Keyword(s):  
Mouse Models ◽  
Ex Vivo ◽  
Joint Inflammation ◽  
Autoinflammatory Syndrome ◽  
Her Family ◽  
Whole Exome ◽  
Urate Crystals

ObjectiveTo explore at the molecular level the phenotype of a patient suffering an autoinflammatory syndrome which was diagnosed as familial cold autoinflammatory syndrome type 2 (FCAS-2). To explore the functions of Nlrp12 in inflammation using mouse models.MethodsWhole exome sequencing and Nlrp12 targeted resequencing were performed on DNA isolated from the patient and her family members. In vivo and ex vivo models of inflammation (urate crystals-dependent acute joint inflammation and urate crystals-induced peritonitis) were analysed in Nlrp12-deficient and Nlrp12-competent mice.ResultsA rare missense NLRP12 variant (c.857C>T, p.P286L) was identified in the patient and her healthy relatives. Nlrp12-deficient mice exhibit reduced systemic inflammation and neutrophilic infiltration.ConclusionNlrp12 mediates proinflammatory functions in mice. In humans, the identification of Nlrp12 variants must be cautiously interpreted depending on clinical and paraclinical data to diagnose FCAS-2.

scholarly journals COVID-19 in Autoinflammatory Diseases with Immunosuppressive Treatment

2021 ◽  
Vol 10 (4) ◽  
pp. 605
Author(s):  
Tatjana Welzel ◽  
Samuel Dembi Samba ◽  
Reinhild Klein ◽  
Johannes N. van den Anker ◽  
Jasmin B. Kuemmerle-Deschner
Keyword(s):  
Immunosuppressive Treatment ◽  
Case Series ◽  
Autoinflammatory Diseases ◽  
Treatment Intensification ◽  
Positive Antibody ◽  
Mediterranean Fever ◽  
Role Of It ◽  
Positive Antibody Response

COVID-19 disease increases interleukin (IL)-1β release. Anti-IL-1-treatment is effective in IL-1-mediated autoinflammatory diseases (AID). This case series presents COVID-19 in patients with IL-1-mediated and unclassified AID with immunosuppressive therapy (IT). Patient 1 is a 34-year-old woman with an unclassified AID and methotrexate. Patients 2 and 3 (14-year-old girl and 12-year-old boy, respectively) have a Cryopyrin-Associated Periodic Syndrome (NLRP3 p.Q703K heterozygous, CAPS) treated with canakinumab 150 mg/month since three and five years, respectively. Patient 4 is a 15-year-old girl who has had familial Mediterranean fever (MEFV p.M694V homozygous) for 3 years treated with canakinumab 150 mg/month and colchicine. All patients had a mild acute COVID-19 course, particularly the adolescent patients. A few weeks after COVID-19 recovery, both CAPS patients developed increased AID activity, necessitating anti-IL-1-treatment intensification in one patient. At day 100, one out of four patients (25%) showed positive antibody response to SARS-CoV-2. This is one of the first reports providing follow-up data about COVID-19 in AID. The risk for severe acute COVID-19 disease was mild/moderate, but increased AID activity post-COVID-19 was detected. Follow-up data and data combination are needed to expand understanding of COVID-19 and SARS-CoV-2 immunity in AID and the role of IT.

scholarly journals AA-amyloidosis in autoinflammatory diseases

2021 ◽  
Vol 31 (4) ◽  
pp. 52-61
Author(s):  
V. Rameev ◽  
S. Moiseev ◽  
L. Lysenko (Kozlovskaya)
Keyword(s):  
Amyloid Fibrils ◽  
Acute Phase Reactant ◽  
Autoinflammatory Diseases ◽  
Aa Amyloidosis ◽  
Chronic Infections ◽  
Amyloid A ◽  
Ankylosing Spondilitis ◽  
Serum Amyloid A Protein ◽  
Treatment Improvement

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.

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