scholarly journals Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

2021 ◽  
Vol 22 (12) ◽  
pp. 6360
Author(s):  
Giulia Di Donato ◽  
Debora Mariarita d’Angelo ◽  
Luciana Breda ◽  
Francesco Chiarelli
Keyword(s):  
Innate Immune ◽  
Sterile Inflammation ◽  
Autoinflammatory Diseases ◽  
Clinical Aspects ◽  
Genetic Sequencing ◽  
Regulatory Pathways ◽  
Interferon Pathway ◽  
Mediterranean Fever ◽  
Encoding Gene ◽  
Nf Kappab

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.

scholarly journals Autoinflammatory diseases

2020 ◽  
Vol 29 (4) ◽  
pp. 49-60
Author(s):  
V.V. Rameev ◽  
L.V. Lysenko (Kozlovskaya) ◽  
M.V. Bogdanova ◽  
S.V. Moiseev
Keyword(s):  
Immune System ◽  
Familial Mediterranean Fever ◽  
Cellular Immunity ◽  
Innate Immune System ◽  
Clinical Manifestations ◽  
Innate Immune ◽  
Autoinflammatory Diseases ◽  
Periodic Syndrome ◽  
Current Classification ◽  
Mediterranean Fever

Autoinflammatory diseases are a group of disorders caused by a dysregulation of the innate immune system. Unlike autoimmune diseases, they are not associated with changes in humoral or cellular immunity. The authors review the current classification, clinical manifestations and treatment of various systemic autoinflammatory diseases, including cryopirinassociated periodic syndrome, familial Mediterranean fever, HIDS, and TRAPS.

scholarly journals Prevalence of Allergic Diseases in Patients with Common Autoinflammatory Diseases

2021 ◽  
Vol 19 (1) ◽  
pp. 32-37
Author(s):  
Tuba Erdoğan ◽  
Nazife Şule yaşar Bilge ◽  
Timuçin Kaşifoğlu
Keyword(s):  
Allergic Rhinitis ◽  
Familial Mediterranean Fever ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Allergic Diseases ◽  
Innate Immune ◽  
Autoinflammatory Diseases ◽  
Behcet's Disease ◽  
Mediterranean Fever

ABSTRACT Objective: Autoinflammatory diseases are driven by abnormal activation of the innate immune system. Although allergic diseases are known to be mediated by the T helper 2 response, new mechanisms are put forward about the activation of innate immunity during exposure to allergens in recent years. Familial Mediterranean fever (FMF) and Behçet’s disease (BD) are the commonly seen autoinflammatory diseases in Turkey. It was aimed to determine the prevalence of allergic diseases in BD and FMF and contribute to explaining the relationship between autoinflammation and allergic diseases in this survey. Materials and Methods: The study included 42 patients with BD, 40 with FMF, 20 with other rheumatic diseases, and 20 healthy controls who had volunteered for allergic evaluation. Patients were questioned about allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, venom allergy, and food-drug allergy. The same prick test panel was used for all patients to investigate the presence of atopy. Results: Although the rate of allergic diseases and the blood eosinophil rate were significantly higher in patients with FMF and Behçet’s disease, which are commonly seen as autoinflammatory diseases, atopy rates were similar in all groups. The prevalence of allergic rhinitis and any allergic diseases was significantly higher in the FMF and BD groups (p: 0.03 and p: 0.02, respectively). In the multiple logistic regression model of the presence of any allergic disease, none of the factors was associated with allergic diseases. Conclusion: The prevalence of allergic diseases in patients with FMF and BD was found to be higher than in those with other rheumatic diseases and the control group but atopy rates were similar in all groups. The autoinflammatory diseases are not protective in terms of allergic sensitization and allergic rhinitis. This may be the result of recent advances in the innate immune sensing system. Keywords: Allergic diseases, autoinflammatory diseases, familial Mediterranean fever, Behçet’s disease, atopy

Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 727-731 ◽  
Author(s):  
Yaacov Matzner ◽  
Suzan Abedat ◽  
Eli Shapiro ◽  
Shlomit Eisenberg ◽  
Ariela Bar-Gil-Shitrit ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Human Fibroblasts ◽  
Skin Fibroblasts ◽  
Sterile Inflammation ◽  
Inhibitor Activity ◽  
Primary Fibroblast ◽  
Fibroblast Cultures ◽  
M694v Mutation ◽  
Human Primary Fibroblast ◽  
Mediterranean Fever

Abstract Familial Mediterranean fever (FMF) is an inherited disease whose manifestations are acute but reversible attacks of sterile inflammation affecting synovial and serosal spaces. The FMF gene (MEFV) was recently cloned, and it codes for a protein (pyrin/marenostrin) homologous to known nuclear factors. We previously reported the deficient activity of a C5a/interleukin (IL)–8 inhibitor, a physiologic regulator of inflammatory processes, in FMF serosal and synovial fluids. We now describe the concomitant expression ofMEFV and C5a/IL-8–inhibitor activity in primary cultures of human fibroblasts. Fibroblasts grown from synovial and peritoneal tissues displayed C5a/IL-8–inhibitor activity that could be further induced with phorbol myristate acetate (PMA) and IL-1β. Very low levels of chemotactic inhibitor were evident in skin fibroblast cultures or in peritoneal and skin fibroblasts obtained from FMF patients. MEFV was expressed in peritoneal and skin fibroblasts at a lower level than in neutrophils and could be further induced by PMA and IL-1β. In the FMF cultures, the MEFV transcript carried the M694V mutation, consistent with the genetic defect found in patients with this disease. MEFV was also expressed in other cell lines that do not produce C5a/IL-8 inhibitor. These findings suggest that human primary fibroblast cultures express MEFV and produce C5a/IL-8–inhibitor activity. The interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor requires further investigation.

scholarly journals Deletion of cftr leads to an excessive neutrophilic response and defective tissue repair in a zebrafish model of sterile inflammation

2019 ◽  
Author(s):  
Audrey Bernut ◽  
Catherine A. Loynes ◽  
R. Andres Floto ◽  
Stephen A. Renshaw
Keyword(s):  
Cystic Fibrosis ◽  
Tissue Repair ◽  
Cell Function ◽  
Immune Cell ◽  
Genetic Disorder ◽  
Innate Immune ◽  
Lung Damage ◽  
Tanshinone Iia ◽  
Sterile Inflammation ◽  
Inflammatory Status

AbstractInflammation-related progressive lung destruction is the leading causes of premature death in cystic fibrosis (CF), a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. However, therapeutic targeting of inflammation has been hampered by a lack of understanding of the links between a dysfunctional CFTR and the deleterious innate immune response in CF. Herein, we used CFTR-depleted zebrafish larvae as an innovative in vivo vertebrate model, mimicking aspects of the inflammatory pathology of CF-related lung, to understand how CFTR dysfunction leads to abnormal inflammatory status in CF.We show that impaired CFTR-mediated inflammation correlates with an exuberant neutrophilic response after injury: CF zebrafish exhibit enhanced and sustained accumulation of neutrophils at wounds. Excessive epithelial oxidative responses drive enhanced neutrophil recruitment towards wounds. Persistence of neutrophils at inflamed sites is associated with impaired reverse migration of neutrophils and reduction in neutrophil apoptosis. As a consequence, the increased number of neutrophils at wound sites causes tissue damage and abnormal tissue repair. Importantly, the pro-resolution molecule Tanshinone IIA successfully re-balances inflammation both by accelerating inflammation resolution and by improving tissue repair in CFTR-deficient animal.Larval zebrafish giving a unique insight into innate immune cell function in CFTR deficiency, our findings bring important new understanding of the mechanisms underlying the inflammatory pathology in CF, which could be addressed therapeutically to prevent inflammatory lung damage in CF patients with potential improvements in disease outcomes.

scholarly journals Clinical aspects of Familial Mediterranean fever

2011 ◽  
Vol 34 (5) ◽  
pp. 355-360 ◽  
Author(s):  
Kiyoshi MIGITA ◽  
Kazunaga AGEMATSU
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Aspects ◽  
Mediterranean Fever

scholarly journals Imaging of Joints and Bones in Autoinflammation

2020 ◽  
Vol 9 (12) ◽  
pp. 4074
Author(s):  
Katharina Ziegeler ◽  
Iris Eshed ◽  
Torsten Diekhoff ◽  
Kay Geert Hermann
Keyword(s):  
Chronic Recurrent Multifocal Osteomyelitis ◽  
Diagnostic Information ◽  
Innate Immune ◽  
Future Research ◽  
Autoinflammatory Disorders ◽  
Comprehensive Overview ◽  
Crystal Deposition ◽  
Imaging Characteristics ◽  
Multifocal Osteomyelitis ◽  
Mediterranean Fever

Autoinflammatory disorders are commonly characterized by seemingly unprovoked systemic inflammation mainly driven by cells and cytokines of the innate immune system. In many disorders on this spectrum, joint and bone involvement may be observed and imaging of these manifestations can provide essential diagnostic information. This review aimed to provide a comprehensive overview of the imaging characteristics for major diseases and disease groups on the autoinflammatory spectrum, including familial Mediterranean fever (FMF), Behçet disease (BD), crystal deposition diseases (including gout), adult-onset Still’s disease (AoSD), and syndromatic synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)/chronic recurrent multifocal osteomyelitis (CRMO). Herein, we discuss common and distinguishing imaging characteristics, phenotypical overlaps with related diseases, and promising fields of future research.

scholarly journals The Mitochondrial Fission Regulator DRP1 Controls Post-Transcriptional Regulation of TNF-α

2021 ◽  
Vol 10 ◽  
Author(s):  
Fushan Gao ◽  
Mack B. Reynolds ◽  
Karla D. Passalacqua ◽  
Jonathan Z. Sexton ◽  
Basel H. Abuaita ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Critical Role ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Proinflammatory Response ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Tnf Α

The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production of proinflammatory cytokines such as IFN-β and IL-1β. Dynamin-related protein 1 (DRP1) promotes mitochondrial fission and quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 and mitochondrial dynamics control innate immune signaling and the proinflammatory response are incompletely understood. Here we show that macrophage DRP1 is a positive regulator of TNF-α production during sterile inflammation or bacterial infection. Silencing macrophage DRP1 decreased mitochondrial fragmentation and TNF-α production upon stimulation with lipopolysaccharide (LPS) or methicillin-resistant Staphylococcus aureus (MRSA) infection. The defect in TNF-α induction could not be attributed to changes in gene expression. Instead, DRP1 was required for post-transcriptional control of TNF-α. In contrast, silencing DRP1 enhanced IL-6 and IL-1β production, indicating a distinct mechanism for DRP1-dependent TNF-α regulation. Our results highlight DRP1 as a key player in the macrophage pro-inflammatory response and point to its involvement in post-transcriptional control of TNF-α production.

scholarly journals M2 Macrophages Serve as Critical Executor of Innate Immunity in Chronic Allograft Rejection

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanwen Zhang ◽  
Zhuonan Li ◽  
Wei Li
Keyword(s):  
Allograft Rejection ◽  
Chronic Rejection ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Solid Organ ◽  
M2 Macrophages ◽  
Innovative Strategies ◽  
Chronic Allograft Rejection

Allograft functional failure due to acute or chronic rejection has long been a major concern in the area of solid organ transplantation for decades. As critical component of innate immune system, the macrophages are unlikely to be exclusive for driving acute or chronic sterile inflammation against allografts. Traditionally, macrophages are classified into two types, M1 and M2 like macrophages, based on their functions. M1 macrophages are involved in acute rejection for triggering sterile inflammation thus lead to tissue damage and poor allograft survival, while M2 macrophages represent contradictory features, playing pivotal roles in both anti-inflammation and development of graft fibrosis and resulting in chronic rejection. Macrophages also contribute to allograft vasculopathy, but the phenotypes remain to be identified. Moreover, increasing evidences are challenging traditional identification and classification of macrophage in various diseases. Better understanding the role of macrophage in chronic rejection is fundamental to developing innovative strategies for preventing late graft loss. In this review, we will update the recent progress in our understanding of diversity of macrophage-dominated innate immune response, and reveal the roles of M2 macrophages in chronic allograft rejection as well.

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