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Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens

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Mohamed H. Shamji, Janice A. Layhadi, Hanisah Sharif, Martin Penagos, Stephen R. Durham

J Allergy Clin Immunol Pract. 2021 Mar 27:S2213-2198(21)00363-9. doi: 10.1016/j.jaip.2021.03.029.

Patients with IgE-mediated rhinoconjunctivitis and/or bronchial asthma who do not respond to symptomatic treatment or have severe side effects are often recommended allergen immunotherapy. Prolonged treatment has shown long-term benefits in patients with moderate to severe allergic rhinitis. The long-term efficacy from allergen immunotherapy represents a decrease in IgE activation of mast cells and tissue eosinophilia, which is accompanied by early induction of regulatory T cells, immune deviation in favor of TH1 responses, and induction of local and systemic IgG and IgA antibodies. These antibodies, whose primary function is to be protective, can prevent the formation of allergen-IgE complex and subsequent activation of the mast cells and TH2 facilitated by IgE.

Some studies demonstrate the importance of innate responses mediated by type 2 dendritic cells and innate lymphoid cells in allergic inflammation. Type 2 dendritic cells and lymphoid cells are regulated by cytokines derived from the respiratory epithelium. New subsets of regulatory cells induced by immunotherapy include:

  • IL-35-producing regulatory T cells,
  • Regulatory B cells,
  • A subset of T follicular regulatory cells, and
  • IL-10-producing group 2 innate lymphoid cells.

These regulatory cells may represent biomarkers that will predict the clinical response to immunotherapy and evaluate the efficacy, safety, and long-term tolerance.

More studies are required to identify candidate biomarkers as a routine immune-monitoring tool for assessing allergen immunotherapy response.

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B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated

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Harsha H Kariyawasam & Louisa K James

Expert Rev Clin Immunol. 2021 Apr 1:1-15. doi: 10.1080/1744666X.2021.1905527. Epub ahead of print.

Allergic rhinitis and chronic rhinosinusitis with nasal polips (CRSwP) are upper airway immunological conditions with complex mechanisms of action. Airway local mucosal B cells are drivers for the conditions, with B cells migrating into the airway mucosa when there is an airway injury.

B-cells are very important in the defense, tissue surveillance, and immune modulation of the upper airways. Allergic rhinitis and CRSwP are two of the upper airway conditions that can be identified as expressing B-cells or dysregulating their function within T2-high mucosal inflammatory states. B cells can drive T2 inflammatory states via functional antibody production and also through interactions with commensal microbes and other recruited inflammatory cells such as Th2 cells and eosinophils, leading to immune amplification and dysregulation.

This review aimed to report the existing knowledge of the key role of B cells in allergic inflammatory upper airway disease and highlight the need for more focus on human B-cell-directed disease-context-specific upper airway studies.

The authors concluded that there is a lack of studies concerning the role of B-cell overexpression and dysfunction, especially those which relate sinonasal infection and mucosal inflammation. It is important to understand how respiratory inflammation, together with augmented or impaired B-cell function, increases and dysregulates immune signaling pathways in allergic rhinitis and CRSwP to develop novel B-cell disease-specific therapeutic interventions with molecular manipulation.

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Chronic Spontaneous Urticaria

The Pathogenesis of Chronic Spontaneous Urticaria: The Role of Infiltrating Cells

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Ana M. Giménez-Arnau, Laurence DeMontojoye, Riccardo Asero, Massimo Cugno, Kanokvalai Kulthanan, Yuhki Yanase, Michihiro Hide, Allen P. Kaplan

J Allergy Clin Immunol Pract. 2021 Apr 3:S2213-2198(21)00374-3. doi: 10.1016/j.jaip.2021.03.033. Epub ahead of print.

In chronic spontaneous urticaria, cutaneous mast cells are activated to initiate the process. There are different triggers, including the hypothesis that it is an autoimmune disease not driven by exposure to an exogenous agent.

It is characterized by a perivascular non-necrotizing cellular infiltrate around small venules of the skin. These infiltrates include CD4+ lymphocytes, Th2 and Th1 subtypes, Th17 cell-derived cytokines, neutrophils, eosinophils, basophils and monocytes, which contribute to the pathogenesis and responsiveness to steroid

This review focuses on each cell’s contribution to the inflammatory response and a view toward developing therapeutic options.

Immunohistochemistry can help reveal the function of each cell within the perivenular infiltrate. Rituximab efficacy is probably due to the prevention of autoantibody synthesis. Corticosteroids inhibit the function of T lymphocytes and eosinophils and prevent egress of most cell types from the bloodstream into tissues.

In the future, there may be studies that include drugs with increasing specificity in the course of urticaria, such as secukinumab (targets IL-17), dupilumab (targets TH-2 dependent cytokines, IL-4 and IL-3), mepolizumab, reslizumab and benralizumab (target TH2 and eosinophil-dependent cytokines), avdoralimab (complement C5a receptor) and lirentelimab (targets Siglec-8 on the surface of mast cells and eosinophils).

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Use of H-1 Antihistamine in Dermatology: More than Itch and Urticaria Control: A Systematic Review

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Chang-Yu Hsieh, Tsen-Fang Tsai

Dermatol Ther (Heidelb). 2021 Apr 12. doi: 10.1007/s13555-021-00524-w. Epub ahead of print.

H1-antihistamines are known for their effects in suppression of pruritus, especially in urticaria. However, there are many other dermatological uses of H1-antihistamines, such as scarring and nonscarring alopecia, acne, Darier disease, eosinophilic dermatoses, paraneoplastic dermatoses, psoriasis, lichen nitidus, radiation dermatitis, skin dysesthesia, and cutaneous malignancies.

This review includes a literature search on articles that report the use of H1-antihistamines.

It is the modulation of the immune system, inflammatory cytokines, and mast cells that explain why H1-antihistamines are effective in some autoimmune conditions, such as Kaposi sarcoma, melanoma, and alopecia areata. Some eosinophilic dermatosis may be relieved with the use of cetirizine and bilastine due to their effects on the chemotaxis of eosinophils. Hydroxyzine, together with GABA receptor agonists, may have an effect on cutaneous dysesthesia. A combination of antihistamines with isotretinoin helps control acne better, probably due to the inhibition of the production of sebum. The reversing vascular effect of histamine seems to be of interest for erythema, edema, and pain control in radiation dermatitis and erythromelalgia.

New properties of antihistamines have also been studied in vitro: antibacterial activity, antiangiogenesis, and antifibrosis.

H1-antihistamines may improve symptoms of some conditions when used alone or in combination with other treatments; however, this evidence is still limited. More studies are needed to assess the efficacy and dosage of H1-antihistamines in other dermatological conditions.

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Systematic review of measures of disease severity in rhinitis

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Andraia R. Li, Kathy Zhang, Priyanka D. Reddy, Shaun A. Nguyen, Amar Miglani, Jacob Fried, Mariam I. Nguyen, Rodney J. Schlosser

Int Forum Allergy Rhinol. 2021 Mar 27. doi: 10.1002/alr.22794. Epub ahead of print.

Rhinitis is an inflammation of the nasal mucosa with itching, sneezing, rhinorrhea, and congestion. It may be classified into allergic rhinitis and nonallergic rhinitis. The ARIA (allergic rhinitis and its impact on asthma) guidelines categorize allergic rhinitis upon intermittent or persistent timing of symptoms and mild, moderate or severe. The objective of this review was to assess if patient-reported outcome measures (PROMs) and clinical physiological measures vary, and which factors impact rhinitis.

A systematic search identified allergic rhinitis and nonallergic rhinitis that reported Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), total nasal symptom score (TNSS), or visual analog scale (VAS) scores, and physiologic measures (peak nasal inspiratory flow and nasal airflow). The relationship between PROMs, physiologic measures, and associated factors was statistically evaluated.

The review included 171 studies, which reflected 33843 patients. Patients with allergic rhinitis had more severe symptoms than nonallergic rhinitis ones. There was no significant correlation between PROMs and demographic factors, comorbidities, or physiologic measures. Statistical analysis identified a correlation between the worse quality of life and shorter disease duration.

In conclusion, patients with rhinitis have a more severe impact in their quality of life in the presence of allergy with variable impact upon specific symptom subdomains. PROMs did not show a correlation with demographic factors, comorbidities, or physiologic measures of nasal airflow.

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