-
Allergologia Et Immunopathologia 2024Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate...
INTRODUCTION
Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate urticaria symptoms by causing mast cell degranulation via neuromediators.
OBJECTIVES
To investigate the frequency of stressful life events and compare psychiatric comorbidities and serum neuromediator levels in patients with CSU who responded to omalizumab with healthy controls.
METHODS
In this cross-sectional study, we included 42 patients with CSU who received at least 6 months of omalizumab treatment and a control group of 42 healthy controls. Stressful life events were evaluated with the Life Events Checklist for DSM-5 (LEC-5). The Depression Anxiety Stress Scale-42 (DASS-42) was used to evaluate depression, anxiety and stress levels. Serum nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and substance P (SP) levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique.
RESULTS
Twenty-six (62%) patients reported at least one stressful life event a median of 3.5 months before the onset of CSU. There were no significant differences in all three variables in the DASS subscales between the patient and control groups. Serum NGF levels were found to be significantly lower in patients with CSU (p <0.001), whereas CGRP levels were found to be significantly higher (p <0.001). There was no significant difference for SP.
CONCLUSIONS
The psychological status of patients with CSU who benefited from omalizumab was similar to that of healthy controls. Omalizumab may affect stress-related neuromediator levels.
Topics: Humans; Omalizumab; Female; Male; Adult; Chronic Urticaria; Cross-Sectional Studies; Middle Aged; Stress, Psychological; Nerve Growth Factor; Anti-Allergic Agents; Substance P; Calcitonin Gene-Related Peptide; Comorbidity; Depression; Mental Disorders
PubMed: 38721949
DOI: 10.15586/aei.v52i3.1015 -
Scientific Reports May 2024To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab...
To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab. We defined clinical response as a reduction in the baseline annual exacerbation rate by half or more over the one-year period following initiation of the biologic. Baseline levels of plasma IL-13 were differentially elevated in responders versus non-responders to mepolizumab and plasma CXCL10 levels were differentially elevated in responders to omalizumab. The ratio of IL-13/TNF-α had the best sensitivity and specificity in predicting response to mepolizumab and CXCL10/CCL17 to omalizumab, and these performed better as predictive biomarkers of response than BEC and IgE. Cytokines and chemokines associated with airway eosinophilia, allergic inflammation, or Th2 inflammation, such as IL-13 and CXCL10, may be better predictors of clinical response to mepolizumab and omalizumab, than IL-5 or IgE, the targets of mepolizumab and omalizumab.
Topics: Humans; Asthma; Antibodies, Monoclonal, Humanized; Omalizumab; Immunoglobulin E; Female; Eosinophils; Male; Chemokine CCL17; Adult; Middle Aged; Chemokine CXCL10; Interleukin-13; Tumor Necrosis Factor-alpha; Biomarkers; Anti-Asthmatic Agents; Leukocyte Count; Treatment Outcome
PubMed: 38710930
DOI: 10.1038/s41598-024-60864-3 -
Respiratory Medicine Jun 2024The prevalence of asthma among the elderly population has witnessed a notable rise, presenting unique challenges in diagnosis and management. Biologic therapies, such as... (Review)
Review
The prevalence of asthma among the elderly population has witnessed a notable rise, presenting unique challenges in diagnosis and management. Biologic therapies, such as omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, have demonstrated efficacy in targeting specific pathways associated with severe asthma in elderly individuals. However, a significant research gap exists in the application of these therapies in elderly asthma patients. Despite the considerable size of the elderly asthma population and the social and economic burden that this specific demographic imposes on society, the available body of research catering to this group is limited. Notably, no RCTs have been expressly designed for the elderly across all asthma biologic therapies. Moreover, most RCTs have set upper age cutoffs, commonly 75 years old, and exclusion criteria for common comorbidities in the elderly, thus marginalizing this group from pivotal research. This underscores the crucial need for intentional inclusion of elderly participants in separately designed clinical trials and more researches, aiming to augment the generalizability of findings and enhance therapeutic outcomes. Given the distinct physiological changes associated with aging, there may be a concern regarding the efficacy and safety of biologic therapies in the elderly compared to non-elderly adults, posing a barrier to their use in this population. However, observational studies have shown similar benefits of these therapies in elderly individuals as seen in non-elderly adults. Other anticipated challenges related to initiating biologic therapy in elderly people with asthma including dosing consideration and monitoring strategies, which are important areas of investigation for optimizing asthma management will be discussed in this review. In summary, this review navigates the current landscape of biologic therapies for elderly asthma, offering valuable insights for various stakeholders, including researchers, healthcare providers, and policymakers, to advance asthma care in this vulnerable population. We propose that future research should concentrate on tailored, evidence-based approaches to address the undertreatment of elderly asthma patients.
Topics: Humans; Asthma; Aged; Biological Therapy; Antibodies, Monoclonal, Humanized; Anti-Asthmatic Agents; Omalizumab; Aged, 80 and over; Male; Female; Age Factors
PubMed: 38679338
DOI: 10.1016/j.rmed.2024.107655 -
Tuberkuloz Ve Toraks Mar 2024Recurrences occur when corticosteroid therapy is discontinued or reduced during the treatment of chronic eosinophilic pneumonia (CEP). The probability of recurrence is...
INTRODUCTION
Recurrences occur when corticosteroid therapy is discontinued or reduced during the treatment of chronic eosinophilic pneumonia (CEP). The probability of recurrence is once in 50% of patients and twice or more in 25%. In such instances, new treatment options are deemed necessary. This study aims to assess the efficacy of omalizumab treatment as a steroid-sparing drug in patients with CEP.
MATERIALS AND METHODS
The clinical features of patients treated with omalizumab for recurrent CEP were evaluated retrospectively before and after treatment. All data from patients and diagnoses were reviewed. The effects of treatment on recurrence rate, oral corticosteroid (OCS) use and lung functions, peripheral eosinophil values, and symptom scores were evaluated. Radiological regression was also evaluated.
RESULT
In the final analysis, we included ten patients with a median follow-up of 22 months after initiation of omalizumab. During this follow-up period, the results were associated with a significant reduction in the number of asthma attacks per year, the number of CEP relapses, the rate of hospitalization, the amount of corticosteroids consumed daily, and the total corticosteroid dose. In addition, improvement was observed in the symptom scores and lung functions of the patients. Systemic steroids were completely discontinued in two patients receiving omalizumab treatment. In other patients, the mean steroid dose was reduced by 77.2 percent in the first year of omalizumab treatment and 82 percent in the second year, respectively. Nevertheless, there was no elevation in peripheral eosinophil count, and radiological regression was observed.
CONCLUSIONS
Omalizumab can be an effective treatment for CEP and can be used as a steroid-sparing agent.
Topics: Humans; Omalizumab; Male; Female; Pulmonary Eosinophilia; Retrospective Studies; Middle Aged; Adult; Treatment Outcome; Chronic Disease; Anti-Asthmatic Agents; Recurrence; Adrenal Cortex Hormones; Aged
PubMed: 38676596
DOI: 10.5578/tt.202401795 -
Vaccines Apr 2024Immune responses to influenza (flu) antigens reflect memory of prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past... (Review)
Review
Immune responses to influenza (flu) antigens reflect memory of prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed "original antigenic sin" or, more recently, "immune imprinting" and "seniority". We have researched a comparison between the immune response to live flu infections and inactivated flu vaccinations. A brief history of antibody generation theories is presented, culminating in new findings about the immune-network theory and suggesting that a network of clones exists between anti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4 memory T cells and cytotoxic CD8 T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells, like natural killer (NK) cells and macrophages, are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes is described. New vaccines in development are mentioned along with the results of some clinical trials. The manuscript concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.
PubMed: 38675771
DOI: 10.3390/vaccines12040389 -
Molecular Biotechnology Apr 2024Using the hybridoma technique, we developed a panel of anti-idiotypic monoclonal antibodies (aId-mAb) that mimic The Severe Acute Respiratory Syndrome Coronavirus 2...
Using the hybridoma technique, we developed a panel of anti-idiotypic monoclonal antibodies (aId-mAb) that mimic The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Receptor-Binding Domain (RBD) molecule against Fragment antigen-binding (Fab) of anti-SARS-CoV-2 (S1, RBD) antibodies. Investigated the in vivo and in vitro effects of these aId-mAbs we developed and examined their antigenic mimicry abilities. Among these 12 antibodies, 6 aId-mAbs (designated FY1B4, FY2A6, H9F3, E6G7, FY7E11, and FY8H3) were selected for further characterization in a series of experiments. First, competitive receptor binding assay results confirmed that six aId-mAbs could specifically bind to the ACE2 receptor in target cells and block the interaction between the RBD molecule and the ACE receptor. Moreover, we examined the immunological activities of these aId-mAbs in female BALB/c and showed that E6G7, H7E11, and H8H3 aId-mAbs induce an antibody response by mimicking RBD and stimulating the immune system. It is considered that these three aId-mAbs will be evaluated as SARS-CoV-2 vaccine candidate molecules in future studies.
PubMed: 38662257
DOI: 10.1007/s12033-024-01138-1 -
Current Opinion in Allergy and Clinical... Jun 2024
Topics: Omalizumab; Humans; Food Hypersensitivity; Anti-Allergic Agents; Immunoglobulin E
PubMed: 38656288
DOI: 10.1097/ACI.0000000000000985 -
Revue Des Maladies Respiratoires May 2024Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the... (Review)
Review
INTRODUCTION
Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules.
STATE OF KNOWLEDGE
Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections.
CONCLUSION
Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians.
Topics: Humans; Asthma; Biological Products; Anti-Asthmatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Omalizumab; France
PubMed: 38653607
DOI: 10.1016/j.rmr.2024.04.001 -
The Journal of Allergy and Clinical... Jun 2024The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United... (Review)
Review
The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.
Topics: Omalizumab; Humans; Food Hypersensitivity; Anti-Allergic Agents; Immunoglobulin E; Practice Guidelines as Topic
PubMed: 38599291
DOI: 10.1016/j.jaci.2024.03.019 -
Journal Der Deutschen Dermatologischen... May 2024
Review
Topics: Humans; Omalizumab; Angioedema; Anti-Allergic Agents; Treatment Outcome; Female; Middle Aged
PubMed: 38593341
DOI: 10.1111/ddg.15359