Autoinflammatory diseases: How to put the fire inside the body out?

doi:10.1016/j.autrev.2012.07.013

Autoimmunity Reviews

Volume 12, Issue 1, November 2012, Pages 1-4

https://doi.org/10.1016/j.autrev.2012.07.013 Get rights and content

Abstract

Autoinflammatory diseases (AIDs) are a group of distinct hereditable disorders characterized by unexplained, recurrent episodes of fever and severe inflammation, most commonly involving skin, joints, gut, and eyes. Mutations in inflammasome-related proteins, particularly in NOD-like receptor (NLR) genes, have been strongly associated with the occurrence of AIDs. However, new genes and dysfunctional proteins have recently been identified and the spectrum of AIDs is ever-expanding. In fact, it has been suggested to encompass other disorders which share some clinical features with AIDs, but are not clearly familial, or are not characterized by fever as a prominent symptom, or are polygenic.

In this issue of Autoimmunity Reviews some novel and burning aspects of AIDs were covered and the relationship between AIDs and autoimmune diseases was discussed.

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2023, Adolescent Psychosis: Clinical and Scientific Perspectives
Inflammation and dysregulated immune responses have been suggested to be involved in the pathophysiology of psychotic disorders, including early-onset psychosis (EOP; illness onset before age 18 years). By having an important role in neurodevelopment and physiological central nervous system maintenance, the immune system participates in the interplay between environmental and genetic factors conferring risk for neuropsychiatric disorders. However, while converging evidence from epidemiological, genetic, and clinical studies in adults with psychotic disorders indicate immune system dysregulation, studies of youth with EOP are scarce. In this chapter, we provide an overview of the immunopsychiatry (i.e., the discipline that studies the connections between human behavior, the brain, and the immune system) of EOP, including potential mechanisms. Further, we review findings from clinical studies of peripheral immune functions among these patients.
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The history of autoimmune diseases (ADs) in humans is more than a century (120 years) old. Within this period, we have seen significant development in the field in terms of their causes (genetics, diet, environmental factors, and the phenomenon of molecular mimicry) responsible for autoantibodies (AutoAbs) and self-reactive T cells. Also, new molecules and signaling pathways (different receptors and their ligands) controlling the immune response have played a significant role in the field. We have discovered various immune cells and their subtypes. Innate lymphoid cells (ILCs) are also one of these immune cells, came to the forefront of immunology in 2009 and 2010, with their discovery in both humans and mice. However, the natural killer (NK) cells, which belong to group 1 ILCs of ILCs have been discovered much earlier (1975) in laboratory mice. Also, the lymphoid tissue inducer (LTi) cells uncovered in 1997 belong to group 3 ILCs. Their discovery has revolutionized the immunology of different inflammatory and infectious diseases, including asthma and helminthic parasitic infections, along with bacterial and viral diseases. ILCs appear as lymphocytes morphologically but work as innate immune cells and express and secrete various immune molecules (cytokines and chemokines) that have the potential to maintain immune homeostasis. Any breach in the ILCs homeostasis has the potential to initiate autoinflammatory and ADs. The present chapter discusses the importance of different types of ILCs (group 1 ILCs, group 2 ILCs, and group 3 ILCs) as crucial components of the immune system, their role in immunity and inflammation, and their impact on different ADs.
Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis
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Citation Excerpt :
Cases of IRAP without plausible immunological causes have been recently related to autoinflammatory disorders, a growing family of innate immunity dysfunctions mainly caused by mutations in genes involved in the inflammatory response, without any apparent involvement of antigen-specific T cells or autoantibodies [45,46]. In particular, a lack of regulation in the inflammasome, a large intracellular multiprotein platform with a central role in innate immunity, can lead to the overproduction of proinflammatory cytokines, such as IL-1β and tumor necrosis factor (TNF)-α, and to a pathological delay in the modulation of inflammation [47–57]. Patients generally display periodically-recurring inflammatory phenomena which have a typical onset in the pediatric age, and classically show increased inflammatory parameters, alternating with symptom-free intervals in which acute-phase reactants are normal [58].
Autoimmunity and autoinflammation are generally considered as mutually exclusive mechanisms of diseases but may concur to specific syndromes. Idiopathic recurrent acute pericarditis (IRAP) is defined as the recurrence of pericardial symptoms at any point following the prior cessation of acute pericarditis, and the latency is generally 6 weeks. Manifestations of pericarditis such as pericardial friction rub, electrocardiographic changes, and pericardial effusion are less frequent in the subsequent episodes compared to the index attack, and in some cases the only clinical sign is represented by a suggestive chest pain. Several autoimmune diseases may manifest with pericarditis which is often related to viral infections, while postviral pericarditis may in turn display a nonspecific autoimmune background. Similarly, autoinflammatory syndromes such as familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome are characterized by self-limiting pericardial symptoms. Corticosteroids are generally effective, thus supporting the autoimmune nature of IRAP, but dramatic results are obtained with interleukin-1 blocking agents in corticosteroid-dependent cases, pointing to a pathogenic role for the inflammasome. Based on these observations, we submit that IRAP represents a paradigmatic example of the putative coexistence of autoimmunity and autoinflammation: the main aim of this review is to critically discuss the hypothesis as well as the current understanding of this enigmatic clinical condition.
Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis
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Citation Excerpt :
Therefore, studies involving larger numbers of patients and longer-term follow-up periods are needed to generate specific therapeutic guidelines. In recent years, the identification of more than ten genes involved in the modulation of inflammatory and apoptotic processes, causing abnormal activation of innate immunity pathways, has allowed the definition of an expanding set of monogenic autoinflammatory syndromes [110–118]. The purpose of this paper has been to focus on the pathogenic, clinical, and therapeutic issues of BS and EOS, with the ultimate goal of increasing clinicians' awareness of these disorders.
Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-α inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders.
Diagnostic criteria of familial Mediterranean fever
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Citation Excerpt :
Autoinflammatory diseases are a group of disorders characterized by seemingly unprovoked inflammation in the absence of infective causes, autoantibodies or auto-reactive T-lymphocytes, that derive from defects in innate immunity [1].
Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, mainly affecting ethnic groups living at Mediterranean basin. FMF is characterized by recurrent, self-limited episodes of fever and serositis. The diagnosis is difficult in the presence of atypical signs, which may result in significant delay in initiating treatment. As autoinflammatory diseases may have overlapping symptoms, strict diagnostic criteria are essential. Since the discovery that mutations in the gene MEFV underlie FMF, molecular genetic testing has been used as a diagnostic adjunct, especially in atypical cases. However, despite progress in the understanding of FMF disease mechanisms during the past 15 years; the diagnosis is still based on clinical criteria. Several sets of diagnostic criteria have been proposed and used. Existing diagnostic criteria should be modified to include genetic data, and need to be more widely validated.
The role of biomarkers in patients with fever of unknown origin and recurrent fever
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Fever of unknown origin (FUO) are defined by a fever greater than 38.3 °C evolving during at least 3 weeks and without diagnosis despite appropriate explorations. This clinical entity is not so uncommon. More than 200 causes of FUO have been reported. Despite medical advances, they remain unexplained in 10 to 30% of cases after exhaustive work-up. So FUO is a challenging medical problem. Clinical evaluation remains the basis of the initial evaluation of the patient with FUO. Newer diagnostic modalities, including blood chemistry, immunological tests and molecular methods have important role in the assessment of these patients. We will discuss in this review terminology, common causes of FUO and technical innovation.
Les fièvres prolongées inexpliquées se définissent comme une fièvre supérieure à 38,3 °C évoluant depuis trois semaines et sans diagnostic malgré des explorations appropriées. Ces fièvres relèvent de causes diverses et nombreuses (plus de 200 répertoriées). Elles restent inexpliquées dans 10 à 30 % des cas malgré un inventaire exhaustif et les progrès des techniques de biologie. Elles relèvent d’un véritable défi diagnostique pour les cliniciens. Si l’examen clinique reste un élément essentiel dans la prise en charge de ces malades et oriente le choix des examens complémentaires, ces fièvres ont bénéficié des importants progrès réalisés dans différents domaines de la biologie : examens biochimiques, immunologie, techniques de biologie moléculaire en microbiologie, diagnostic génétique. Dans cet article nous traiterons des fièvres prolongées inexpliquées ainsi que des fièvres récurrentes. Après avoir rappelé la terminologie et les différentes causes de ces fièvres, nous passerons en revue les innovations techniques qui sont intervenues ces dernières décennies.

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^☆: The authors declare no conflict of interest.

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ReviewAutoinflammatory diseases: How to put the fire inside the body out?☆

Abstract

Autoimmun Rev

Autoimmun Rev

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Systemic juvenile idiopathic arthritis. Autoimmun Rev:

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Review
Autoinflammatory diseases: How to put the fire inside the body out?☆