Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases ...encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long‐lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker‐driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.
The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted ...treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.
Background
While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This ...results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment.
Objective
We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells.
Methods
We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels.
Results
SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2+ and IgG4+ memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement.
Conclusion
Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
This study examines the effect of ryegrass pollen AIT on B‐cell responses in a population of 29 patients with allergic rhinitis. Successful immunotherapy for ryegrass pollen allergy increases allergen‐specific IgG2 and IgG4 serum levels, and proportions of IgG2‐ and IgG4‐expressing memory B cells. Skewing toward the anti‐inflammatory IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
Activin A, a member of the transforming growth factor-β superfamily of cytokines, is a critical controller of inflammation, immunity and fibrosis. It is rapidly released into the blood following a ...lipopolysaccharide challenge in experimental animals, through activation of the Toll-like receptor 4 signalling pathway. Blocking activin action by pre-treatment with its binding protein, follistatin, modifies the inflammatory cytokine cascade, and reduces the severity of the subsequent inflammatory response and mortality. Likewise, high serum levels of activin A are predictive of death in patients with septicaemia. However, activin A has complex immunomodulatory actions. It is produced by inflammatory macrophages, but can regulate either pro- or anti-inflammatory responses in these cells, depending on their prior activation status. Activin A is also produced by Th2 cells, and stimulates antibody production by B cells and the development of regulatory T cells. Production of activin A during inflammatory responses stimulates fibrosis and tissue remodelling, and follistatin inhibits these actions of activin A. The modulation of activin by follistatin may represent an important therapeutic target for the modulation and amelioration of inflammatory and fibrotic disorders.
Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. ...Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM
or IgG1
and continued to rise until 150 days. RBD-specific IgG
Bmem were predominantly CD27
, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.
The Melbourne thunderstorm asthma epidemic in November 2016 was unprecedented in scale and impact. We systematically reviewed our hospital's patients with thunderstorm asthma to identify key risk ...factors. Of 85 adult patients assessed, the majority (60%) had no prior diagnosis of asthma. However, allergic rhinitis during the grass pollen season was almost universal (99%), as were ryegrass pollen sensitization (100%) and exposure to the outdoor environment during the thunderstorm (94%). Airborne pollen levels on the thunderstorm day were extreme. We conclude that ryegrass pollen sensitization, clinical allergic rhinitis, and acute allergen exposure constitute a risk-factor ‘trifecta’ for thunderstorm asthma.
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•Ryegrass pollen sensitizsation, allergic rhinitis and allergen exposure are a risk ‘trifecta’ for thunderstorm asthma.•In contrast, the majority (60%) of patients presenting with thunderstorm asthma did not have a prior diagnosis of asthma.•The development of public health measures to target these identified key risk factors are essential to mitigate future risk.
IgE in allergy: It takes two von Borstel, Anouk; O'Hehir, Robyn E; van Zelm, Menno C
Science translational medicine,
02/2024, Volume:
16, Issue:
733
Journal Article
Peer reviewed
A type 2 memory B cell subset is poised to differentiate into IgE-producing plasma cells in individuals with allergies (Ota
. and Koenig
.).
Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The ...scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
Background
IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen‐specific ...IgG2 levels after a 3rd consecutive pre‐seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen‐specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM‐AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders.
Methods
Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae‐specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub‐group of individuals enrolled in a randomized, double‐blind, placebo‐controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet.
Results
After 1‐year sublingual AIT, HDM‐specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM‐specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM‐AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM‐specific IgG2 and IgE responses is only observed in individuals stratified as high responders.
Conclusions
We provide evidence for coordinated serum immune responses upon AIT in HDM‐allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM‐specific IgE, IgG2, and IgG4 in serum could be used as follow‐up combined markers to support decision as to AIT continuation and/or adaptation.
This study assesses humoral responses in HDM‐allergic individuals beforeand after 1‐year HDM tablet sublingual AIT. Individuals suffering from HDM allergy exhibit an increase in serum HDM‐specific IgG2 following 1‐year AIT. Correlations observed between changes in IgG2 and IgE antibody levels highlight coordinated humoral responses only in high responders during AIT.
Abbreviations: AIT, allergen immunotherapy; HDM, house dust mite; IR, index of reactivity
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