Current Understanding of Immune Thrombocytopenia: A Review of Pathogenesis and Treatment Options

Mititelu A, Onisâi MC, Roșca A, Vlădăreanu AM. Int J Mol Sci. 2024 Feb 10;25(4):2163. doi: 10.3390/ijms25042163. 

Abstract

Pathogenesis of immune thrombocytopenia and targets for drug action

The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients’ quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking. The actual management of ITP is based on immune suppression (corticosteroids and intravenous immunoglobulins), or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors.

Determinants of immunoglobulin G responses to respiratory syncytial virus and rhinovirus in children and adults

Guillien A, Niespodziana K, Mauclin M, Boudier A, Varraso R, Leynaert B, Dumas O, Le Moual N, Schlederer T, Bajic M, Borochova K, Errhalt P, Vernet R, Nadif R, Bousquet J, Bouzigon E, Valenta R, Siroux V.  Front Immunol. 2024 Mar 4;15:1355214. doi: 10.3389/fimmu.2024.1355214.

Abstract

Introduction: Exposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults.

Methods: The study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels.

Associations of RSV and RV-specific IgG levels with personal determinants and seasons
of blood sampling in children (EGEA1, n=531) and adults (EGEA2, n=1241). 

Results: In children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels.

Comparison of the therapeutic effects of medication therapy, specific immunotherapy and anti-IgE (Omalizumab) in patients with hay fever.

Tang R, Lyu X, Hou Y, Yang Y, Fu G, Zhu L, Xue L, Li H, Wang R. Front Immunol. 2024 Feb 28;15:1363034. doi: 10.3389/fimmu.2024.1363034. 

Background: Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever.

Methods: Conducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes.

VAS score, symptom score, and medication score before and after treatment of three therapies
on hay fever patients.

Results: Compared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group.

Coupling of a Major Allergen to the Surface of Immune Cells for Use in Prophylactic Cell Therapy for the Prevention of IgE-Mediated Allergy.

Mengrelis K, Niederacher G, Prickler L, Kainz V, Weijler AM, Rudolph E, Stanek V, Eckl-Dorna J, Baranyi U, Spittler A, Focke-Tejkl M, Bohle B, Valenta R, Becker CFW, Wekerle T, Linhart B.  Cells. 2024 Mar 3;13(5):446. doi: 10.3390/cells13050446.

Abstract

Biochemical analysis of recombinant and lipidated Phl p 5 allergens. A–C Analysis of Phl p 5 for EDC coupling. 

Up to a third of the world’s population suffers from allergies, yet the effectiveness of available preventative measures remains, at large, poor. Consequently, the development of successful prophylactic strategies for the induction of tolerance against allergens is crucial. In proof-of-concept studies, our laboratory has previously shown that the transfer of autologous hematopoietic stem cells (HSC) or autologous B cells expressing a major grass pollen allergen, Phl p 5, induces robust tolerance in mice. However, eventual clinical translation would require safe allergen expression without the need for retroviral transduction. Therefore, we aimed to chemically couple Phl p 5 to the surface of leukocytes and tested their ability to induce tolerance. Phl p 5 was coupled by two separate techniques, either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) or by linkage via a lipophilic anchor, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide (DSPE-PEG-Mal).

Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma

Joulia R, Puttur F, Stölting H, Traves WJ, Entwistle LJ, Voitovich A, Garcia Martín M, Al-Sahaf M, Bonner K, Scotney E, Molyneaux PL, Hewitt RJ, Walker SA, Yates L, Saglani S, Lloyd CM.  J Clin Invest. 2024 Mar 15;134(6):e173676. doi: 10.1172/JCI173676.

Abstract

Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas.

Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation

Chen N, Xie QM, Song SM, Guo SN, Fang Y, Fei GH, Wu HM.  Int Immunopharmacol. 2024 Mar 8;131:111791. doi: 10.1016/j.intimp.2024.111791. 

Abstract

Purpose

Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation.

Methods

Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed.

Results

DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review

Luciano Ibba, Luigi Gargiulo, Carlo Alberto Vignoli, Giovanni Fiorillo, Mario Valenti, Antonio Costanzo & Alessandra Narcisi . Clinical, Cosmetic and Investigational Dermatology, 17:, 593-604, DOI: 10.2147/CCID.S329442 

Abstract

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria

Bhatia D, Mehta H, Bishnoi A, Srivastava N, Vinay K, Parsad D, Kumaran MS. Asia Pac Allergy. 2024 Mar;14(1):5-11. doi: 10.5415/apallergy.0000000000000132.

Abstract

Background:

Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive.

Objective:

To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients.

Methods:

This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response.