Clinical Reviews in Allergy & Immunology最新文献

Systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and Sjögren's syndrome are four major autoimmune rheumatic diseases characterized by the presence of autoantibodies, caused by a dysregulation of the immune system that leads to a wide variety of clinical manifestations. These conditions present complex etiologies strongly influenced by multiple environmental and genetic factors. The human leukocyte antigen (HLA) region was the first locus identified to be associated and still represents the strongest susceptibility factor for each of these conditions, particularly the HLA class II genes, including DQA1, DQB1, and DRB1, but class I genes have also been associated. Over the last two decades, the genetic component of these disorders has been extensively investigated and hundreds of non-HLA risk genetic variants have been uncovered. Furthermore, it is widely accepted that autoimmune rheumatic diseases share molecular disease pathways, such as the interferon (IFN) type I pathways, which are reflected in a common genetic background. Some examples of well-known pleiotropic loci for autoimmune rheumatic diseases are the HLA region, DNASEL13, TNIP1, and IRF5, among others. The identification of the causal molecular mechanisms behind the genetic associations is still a challenge. However, recent advances have been achieved through mouse models and functional studies of the loci. Here, we provide an updated overview of the genetic architecture underlying these four autoimmune rheumatic diseases, with a special focus on the HLA region.

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 10⁹/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies.

Frailty is a new concept in rheumatology that can help identify people more likely to have less favorable outcomes. Sarcopenia and inflammaging can be regarded as the biological foundations of physical frailty. Frailty is becoming more widely accepted as an indicator of ageing and is linked to an increased risk of negative outcomes such as falls, injuries, and mortality. Frailty identifies a group of older adults that seem poorer and more fragile than their age-matched counterparts, despite sharing similar comorbidities, demography, sex, and age. Several studies suggest that inflammation affects immune-mediated pathways, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and by disrupting homeostatic signaling. Frailty is more common in the community-dwelling population as people get older, ranging from 7 to 10% in those over 65 years up to 40% in those who are octogenarians. Different parameters have been validated to identify frailty. These primarily relate to two conceptual models: Fried's physical frailty phenotype and Rockwood's cumulative deficit method. Immune-mediated rheumatic diseases (IMRDs), such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, and vasculitis, are leading causes of frailty in developing countries. The aim of this review was to quantitatively synthesize published literature on the prevalence of frailty in IMRDs and to summarize current evidence on the relevance and applicability of the most widely used frailty screening tools.

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

Osteoarthritis is a highly prevalent disease particularly in subjects over 65 years of age worldwide. While in the past it was considered a mere consequence of cartilage degradation leading to anatomical and functional joint impairment, in recent decades, there has been a more dynamic view with the synovium, the cartilage, and the subchondral bone producing inflammatory mediators which ultimately lead to cartilage damage. Inflammaging is defined as a chronic, sterile, low-grade inflammation state driven by endogenous signals in the absence of infections, occurring with aging. This chronic status is linked to the production of reactive oxygen species and molecules involved in the development of age-related disease such as cancer, diabetes, and cardiovascular and neurodegenerative diseases. Inflammaging contributes to osteoarthritis development where both the innate and the adaptive immune response are involved. Elevated systemic and local inflammatory cytokines and senescent molecules promote cartilage degradation, and antigens derived from damaged joints further trigger inflammation through inflammasome activation. B and T lymphocyte populations also change with inflammaging and OA, with reduced regulatory functions, thus implicating self-reactivity as an additional mechanism of joint damage. The discovery of the underlying pathogenic pathways may help to identify potential therapeutic targets for the management or the prevention of osteoarthritis. We will provide a comprehensive evaluation of the current literature on the role of inflammaging in osteoarthritis and discuss the emerging therapeutic strategies.

The immune system is the central regulator of tissue homeostasis, ensuring tissue regeneration and protection against both pathogens and the neoformation of cancer cells. Its proper functioning requires homeostatic properties, which are maintained by an adequate balance of myeloid and lymphoid responses. Aging progressively undermines this ability and compromises the correct activation of immune responses, as well as the resolution of the inflammatory response. A subclinical syndrome of "homeostatic frailty" appears as a distinctive trait of the elderly, which predisposes to immune debilitation and chronic low-grade inflammation (inflammaging), causing the uncontrolled development of chronic and degenerative diseases. The innate immune compartment, in particular, undergoes to a sequela of age-dependent functional alterations, encompassing steps of myeloid progenitor differentiation and altered responses to endogenous and exogenous threats. Here, we will review the age-dependent evolution of myeloid populations, as well as their impact on frailty and diseases of the elderly.

Local anesthetics (LA) are commonly used in procedures and in topical agents for pain management. With the increasing use of LA drugs, the management of LA reactions is more frequently encountered in the office and in operating rooms. True allergic reactions involving IgE-mediated reactions and anaphylaxis are rare; they have only been identified in case reports and account for less than 1% of adverse LA reactions. Most reactions are non-allergic or are a result of hypersensitivity to other culprits such as preservatives, excipients, or other exposures. LA reactions that are misclassified as true allergies can lead to unnecessary avoidance of LA drugs or delays in surgical procedures that require their use. A detailed history of prior LA reactions is the first and most crucial step for understanding the nature of the reaction. Reactions that are suspicious for an immediate hypersensitivity reaction can be evaluated with skin prick and intradermal testing with subsequent graded challenge. Reactions that are suspicious for a delayed hypersensitivity reaction can be evaluated with patch testing.

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health.

The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. Increasing reports have linked changes in this microbiome to a range of pulmonary and extrapulmonary disorders, including asthma, chronic obstructive pulmonary disease and rheumatoid arthritis. Central to many of these findings is the role of IL-17-type immunity as an important driver of inflammation. Despite the crucial role played by IL-17-mediated immune responses in protection against infection, overt Th17 cell responses have been implicated in the pathogenesis of several chronic inflammatory diseases. However, our knowledge of the influence of bacteria that commonly colonise the respiratory tract on IL-17-driven inflammatory responses remains sparse. In this article, we review the current knowledge on the role of specific members of the airway microbiota in the modulation of IL-17-type immunity and discuss how this line of research may support the testing of susceptible individuals and targeting of inflammation at its earliest stages in the hope of preventing the development of chronic disease.

In December 2019, the COVID-19 pandemic quickly spread throughout China and beyond, posing enormous global challenges. With prompt, vigorous, and coordinated control measures, mainland China contained the spread of the epidemic within two months and halted the epidemic in three months. Aggressive containment strategy, hierarchical management, rational reallocation of resources, efficient contact tracing, and voluntary cooperation of Chinese citizens contributed to the rapid and efficient control of the epidemic, thus promoting the rapid recovery of the Chinese economy. This review summarizes China's prevention and control strategies and other public health measures, which may provide a reference for the epidemic control in other countries.