Hasil untuk "Immunologic diseases. Allergy"

Ruchong Chen, L. Sang, Mei Jiang et al.

Background Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. Objective We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. Methods A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. Conclusions Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.

Jan Stępniak, Katarzyna Wojciechowska-Durczyńska, Małgorzata Karbownik-Lewińska

Taoxun Zhou, Bingying Zhang, Runxin Zhu et al.

Macrophages execute host defense against pathogens by releasing extracellular traps (METs) composed of DNA meshwork and antimicrobial proteins. Although MET-mediated pathogen immobilization is well documented, the induction mechanisms of MET generation by helminth parasites remain elusive. Here, we demonstrate that Strongyloides stercoralis larvae induce rapid chromatin extrusion in murine macrophages. Unlike neutrophil extracellular trap (NET) formation, MET formation does not require NADPH oxidase and exhibits distinct ultrastructural characteristics, including endoplasmic reticulum vesiculation, perinuclear space dilation, and inner nuclear membrane budding. Phosphoproteomic analysis revealed that MET formation is coordinately regulated by ERK and AKT signaling, F-actin cytoskeletal remodeling, histone acetylation, and phosphorylation of nuclear envelope (NE) proteins. Specifically, we show that protein kinase C zeta isoform (PKCζ)-mediated lamin A/C phosphorylation drives the NE budding and subsequent DNA expulsion. This work represents the first systematic delineation of the cellular dynamics and molecular machinery underlying MET formation, providing new insights into macrophage-directed anti-helminth immunity.

Jessica M. Scott, Jessica M. Scott, Zhuyu Qiu et al.

We assessed the safety, tolerability, and effects of exercise therapy in three patients with cancer and hospitalization for SARS-CoV-2 infection in an early-phase prospective trial. All study assessments and exercise sessions were conducted remotely (decentralized) in patient’s homes. Patients received five escalated doses of aerobic exercise therapy (range, 90 to 375 minutes per week) following a tolerability-based adapted schedule over 30 consecutive weeks. Exercise therapy was safe (i.e., no serious adverse events), tolerable (i.e., all exercise therapy doses were completed, with an overall average relative exercise dose intensity of 89%), and associated with improvements in patient physiology (e.g., exercise capacity) and patient-reported outcomes (e.g., quality of life). Correlative proteomic and single-cell immune sequencing of peripheral blood samples revealed marked alterations in protein and immune phenotypes implicated in post COVID-19 condition. (ClinicalTrials.gov number, NCT04824443).

A. Leung, Yuhan Xing, MM Fernandez‐Rivas et al.

Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.

Swapna Vijayan, Venkataramana Kandi, Pratyusha S Palacholla et al.

Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.

Philippe Bégin, S. Waserman, Jennifer L. P. Protudjer et al.

Food allergy is defined as an adverse immunologic response to a food. Immunoglobulin E (IgE)-mediated reactions to foods are associated with a broad range of signs and symptoms that may involve any of the following body systems: the skin, gastrointestinal tract, respiratory tract, and cardiovascular system. IgE-mediated food allergy is a leading cause of anaphylaxis. Therefore, timely and appropriate diagnosis and treatment are imperative. A diagnosis of food allergy entails a careful history and diagnostic tests, which may include skin prick tests, serum-specific IgE, and oral food challenge. The goal of food allergy care is to empower patients and caregivers to manage the risk of food-allergic reactions, reduce food allergy-related anxiety, and achieve a sense of control over their condition. This can be achieved in different ways for different patients and across different life stages. This article provides an overview of the epidemiology, pathophysiology, diagnosis, and management of IgE-mediated food allergy. Food allergy is defined as an adverse immunologic response to a food protein. Diagnosis of food allergy requires a detailed history and diagnostic tests, such as SPT and/or food-specific serum IgE measurement, and in some cases, OFCs. Management of food allergy involves avoidance of the culprit food(s) and self-injectable epinephrine for anaphylaxis. For patients with systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh. OIT is indicated as an option for food allergy management, which can be disease-modifying when performed early in the first years of life (see OIT article in this supplement). However, OIT is not readily accessible in many regions. Food allergy is defined as an adverse immunologic response to a food protein. Diagnosis of food allergy requires a detailed history and diagnostic tests, such as SPT and/or food-specific serum IgE measurement, and in some cases, OFCs. Management of food allergy involves avoidance of the culprit food(s) and self-injectable epinephrine for anaphylaxis. For patients with systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh. OIT is indicated as an option for food allergy management, which can be disease-modifying when performed early in the first years of life (see OIT article in this supplement). However, OIT is not readily accessible in many regions.

Joseph Gregory Rosen, Robert Ssekubugu, Larry W. Chang et al.

Abstract Introduction Population‐level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale‐up. Methods In 2015–2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population‐based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low‐level (200–999 copies/ml) or high‐level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit‐pairs; ∼18‐month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow‐up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community‐level prevalence and individual‐level predictors of persistent high‐level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. Results Overall, 3080 participants contributed 4604 visit‐pairs over three survey rounds. Most visit‐pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow‐up, 91.3% of which was high‐level viraemia. One‐fifth (20.8%) of visit‐pairs exhibiting persistent high‐level viraemia self‐reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high‐level viraemia varied substantially across communities and was significantly elevated among young persons aged 15–29 years (vs. 40‐ to 49‐year‐olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21–3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87–3.07), persons reporting inconsistent condom use with non‐marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10–1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03–1.16). The prevalence of persistent high‐level viraemia was highest among males <30 years (32.0%). Conclusions Following universal ART provision, most persons living with HIV in south‐central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high‐level viraemia for ≥12 months and reported higher‐risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

Jiajie Jing, Yuan Ma, Ziwen Xie et al.

Acute lymphoblastic leukemia (ALL) is a prevalent malignancy affecting the hematopoietic system, encompassing both B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL, characterized by the proliferation of T-cell progenitors in the bone marrow, presents significant treatment challenges, with patients often experiencing high relapse rates and poor long-term survival despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT). This review explores the pathogenesis and traditional treatment strategies of T-ALL, emphasizing the promising potential of chimeric antigen receptor (CAR) technology in overcoming current therapeutic limitations. CAR therapy, leveraging genetically modified immune cells to target leukemia-specific antigens, offers a novel and precise approach to T-ALL treatment. The review critically analyzes recent developments in CAR-T and CAR-NK cell therapies, their common targets, optimization strategies, clinical outcomes, and the associated challenges, providing a comprehensive overview of their clinical prospects in T-ALL treatment.

S. Sindher, Alessandro Fiocchi, T. Zuberbier et al.

The landscape of food allergy (FA) treatment is poised for a paradigm shift with the emergence of biologic therapies. The FDA approval of a standardized peanut Powder for oral immunotherapy (OIT) in 2020 marked a milestone, signaling a departure from allergen avoidance toward proactive treatment strategies. While OIT has been proven effective in desensitizing patients to specific allergens, there are several limitations such as lacking standardization, a long-time commitment to achieve maintenance, and adverse events. Biologics, including omalizumab, dupilumab, and anti-alarmins, have shown promise in treating various allergic diseases, including FA. These biologics target the underlying immunological pathways driving allergic reactions, offering an antigen-agnostic approach. Omalizumab (anti-IgE) has been the most studied biologic in this space and can be utilized both as an adjunct therapy with OIT or as monotherapy. Dupilumab targeting IL-4 and IL-13 also shows promise as an adjunct therapy. The emergence of anti-alarmins further broadens the spectrum of FA treatment possibilities. Biologics represent a transformative approach to FA treatment, directly addressing the underlying mechanisms. Future research should focus on patient selection criteria, personalized biomarker panels, optimal timing of intervention, and treatment durations.

E. Lee, A. Copaescu, J. Trubiano et al.

Across all settings, adult females self-report more drug allergies than adult males. Although there is epidemiological evidence of increased drug allergy labeling in post-pubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHR), particularly in fatal drug-induced anaphylaxis, is low. Focusing on the known immunological mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, where a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we aim to describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.

E Orecchini, ML Belladonna, MT Pallotta et al.

Indoleamine 2,3 dioxygenase 1 (IDO1), a leader tryptophan-degrading enzyme, represents a recognized immune checkpoint molecule. In neoplasia, IDO1 is often highly expressed in dendritic cells infiltrating the tumor and/or in tumor cells themselves, particularly in human melanoma. In dendritic cells, IDO1 does not merely metabolize tryptophan into kynurenine but, after phosphorylation of critical tyrosine residues in the non-catalytic small domain, it triggers a signaling pathway prolonging its immunoregulatory effects by a feed-forward mechanism. We here investigated whether the non-enzymatic function of IDO1 could also play a role in tumor cells by using B16-F10 mouse melanoma cells transfected with either the wild-type Ido1 gene (Ido1WT) or a mutated variant lacking the catalytic, but not signaling activity (Ido1H350A). As compared to the Ido1WT-transfected counterpart (B16WT), B16-F10 cells expressing Ido1H350A (B16H350A) were characterized by an in vitro accelerated growth mediated by increased Ras and Erk activities. Faster growth and malignant progression of B16H350A cells, also detectable in vivo, were found to be accompanied by a reduction in tumor-infiltrating CD8+ T cells and an increase in Foxp3+ regulatory T cells. Our data, therefore, suggest that the IDO1 signaling function can also occur in tumor cells and that alternative therapeutic approach strategies should be undertaken to effectively tackle this important immune checkpoint molecule.

Yanbing Wang, Yanbing Wang, Zhenkui Sun et al.

PurposeThe imaging diagnosis of fracture-related infection is often challenging. The aim of this study was to evaluate the value of 18F-FDG PET/CT for the diagnosis of fracture-related infection (FRI) with internal fixation after orthopedic surgery in lower extremities.MethodsA total of 254 consecutive patients who underwent 18F-FDG PET/CT scans with suspected FRI with internal fixation in lower extremities were retrospectively investigated 18F-FDG PET/CT images were semiquantitatively evaluated with multiple metabolic parameters. Additionally, morphological information of the inguinal draining lymph nodes (DLN) with the highest SUV value was also collected and analyzed.ResultsPatients were divided into two groups according to final diagnosis: the infected (N=197) and the non-infected group (N=57). The differences in the inguinal DLN-related parameters, including the long diameter, short diameter, maximum cross-sectional area, maximum standardized uptake value (SUVmax), metabolic volume (MV) 60%, MV70%, MV80%, total lesional glycolysis (TLG) 60%, TLG70%, TLG80%, and the infection suspected area related parameters, including SUVmax, MV25%, MV30%, MV35%, MV40%, MV50%, and TLG70%, between the two groups were statistically significant. We then compared the highest area under the curves (AUCs) among the morphological parameters of DLN, metabolic parameters of DLN, and metabolic parameters of the suspected infection area. The result demonstrated that SUVmax of the inguinal DLN showed the best diagnostic performance with an AUC of 0.939 (P&lt;0.05).ConclusionSemiquantitative analysis (especially SUVmax) of the inguinal DLN in 18F-FDG PET/CT images could be a promising method for the diagnosis of suspected FRI with internal fixation after orthopedic surgery in lower extremities.

Thomas Belcher, Christine S. Rollier, Christina Dold et al.

Neisseria gonorrheoae is the causative agent of gonorrhea, a sexually transmitted infection responsible for a major burden of disease with a high global prevalence. Protective immunity to infection is often not observed in humans, possible due to high variability of key antigens, induction of blocking antibodies, or a large number of infections being relatively superficial and not inducing a strong immune response. N. gonorrhoeae is a strictly human pathogen, however, studies using mouse models provide useful insights into the immune response to gonorrhea. In mice, N. gonorrhoea appears to avoid a protective Th1 response by inducing a less protective Th17 response. In mouse models, candidate vaccines which provoke a Th1 response can accelerate the clearance of gonococcus from the mouse female genital tract. Human studies indicate that natural infection often induces a limited immune response, with modest antibody responses, which may correlate with the clinical severity of gonococcal disease. Studies of cytokine responses to gonococcal infection in humans provide conflicting evidence as to whether infection induces an IL-17 response. However, there is evidence for limited induction of protective immunity from a study of female sex workers in Kenya. A controlled human infection model (CHIM) has been used to examine the immune response to gonococcal infection in male volunteers, but has not to date demonstrated protection against re-infection. Correlates of protection for gonorrhea are lacking, which has hampered the progress towards developing a successful vaccine. However, the finding that the Neisseria meningitidis serogroup B vaccines, elicit cross-protection against gonorrhea has invigorated the gonococcal vaccine field. More studies of infection in humans, either natural infection or CHIM studies, are needed to understand better gonococcal protective immunity.

C. Warren, E. Brown, Julie Wang et al.

A growing body of epidemiological data indicates that the prevalence and public health burden of asthma and other common allergic conditions (e.g. atopic dermatitis, food allergy, allergic rhinitis, drug allergy) is greatest among certain historically marginalized populations. However, these historically marginalized populations are often under-represented in research aiming to better understand, treat and prevent these chronic conditions, raising concerns about the generalizability of the resulting study findings to those who are most affected. In a country as heterogeneous as the United States, with respect to race/ethnicity, socioeconomic status, culture, geography, and behavior, researchers aiming to characterize the burden of allergic disease, evaluate treatments, and/or better understand its mechanisms must pay particular attention to whether their samples are sufficiently diverse and representative in order to maximize the validity-and scientific utility-of the resulting data. Therefore, the goal of this clinical commentary is to highlight the need for improved, more thoughtful representation of the full diversity of affected populations in allergy/immunology research and share best practices for study design, recruitment, retention, and data analysis, so that both the research process and products can have maximal public health impact.

F. Cardinale, G. Ciprandi, S. Barberi et al.

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Guadalein Tanunliong, Aaron C. Liu, Samantha Kaweski et al.

BackgroundOlder adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age.MethodsTo assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets.ResultsSamples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally.ConclusionMost people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.

Adeeb A. Bulkhi, MD, MSc, Ahmad A. Mirza, MBBS, MSc, Abdullah J. Aburiziza, MD, ABP et al.

Allergic fungal rhinosinusitis (AFRS) is a highly resistant disease and is challenging to treat. Patients with recurrent attacks of the disease despite surgical management can benefit from biologics as adjunct therapies. Dupilumab has shown promising endpoints in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). This case series reports 4 patients with resistant AFRS concomitant with asthma, for which dupilumab therapy was administered. Long-term follow-ups showed that dupilumab improved the symptoms and improved the results of objective tools such as imaging and pulmonary function test.

D. Schwartz, M. M. Kitakule, Brian LP Dizon et al.

Background Monogenic autoinflammatory diseases (AID) are caused by mutations in innate immune genes. The effects of these mutations on allergic inflammation are unknown. Objectives We investigated allergic, immunological and clinical phenotypes in FMF (familial Mediterranean fever), CAPS (cryopyrin-associated periodic syndrome), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), HIDS (hyper-IgD syndrome), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), CANDLE (chronic atypical neutrophilic dermatosis, lipodystrophy, elevated temperature) and SAVI (STING-associated vasculopathy of infancy). Methods In this cross-sectional study, clinical data were assessed in 425 patients with AID using questionnaires and chart reviews. Comparator data were obtained from public databases. Peripheral blood mononuclear cells obtained from 55 patients were stimulated and CD4+ cytokine production assessed. Results Clinical laboratory features of Type 2 immunity were elevated in CAPS but reduced in most AID, particularly DADA2. Physician-diagnosed allergic diseases were prevalent in multiple AID, including CAPS and DADA2. T helper 2 (Th2) cells were expanded in CAPS, TRAPS and HIDS; Th9 cells were expanded in HA20. Conclusions CAPS is characterised by an enhanced Type 2 signature, whereas FMF and CANDLE are associated with reduced Type 2 responses. DADA2 is associated with reduced Type 2 responses but a high rate of physician-diagnosed allergy. Therefore, NLRP3-driven autoinflammation may promote Type 2 immunity, whereas AID like DADA2 may manifest clinical phenotypes that masquerade as allergic disorders. Further investigations are needed to determine the contribution of autoinflammation to allergic clinical and immunological phenotypes, to improve the treatment of patients with AID.

Judith Zandstra, Judith Zandstra, Ilse Jongerius et al.

Febrile patients, suffering from an infection, inflammatory disease or autoimmunity may present with similar or overlapping clinical symptoms, which makes early diagnosis difficult. Therefore, biomarkers are needed to help physicians form a correct diagnosis and initiate the right treatment to improve patient outcomes following first presentation or admittance to hospital. Here, we review the landscape of novel biomarkers and approaches of biomarker discovery. We first discuss the use of current plasma parameters and whole blood biomarkers, including results obtained by RNA profiling and mass spectrometry, to discriminate between bacterial and viral infections. Next we expand upon the use of biomarkers to distinguish between infectious and non-infectious disease. Finally, we discuss the strengths as well as the potential pitfalls of current developments. We conclude that the use of combination tests, using either protein markers or transcriptomic analysis, have advanced considerably and should be further explored to improve current diagnostics regarding febrile infections and inflammation. If proven effective when combined, these biomarker signatures will greatly accelerate early and tailored treatment decisions.