Relevance of the Basophil High-Affinity IgE Receptor in Chronic Urticaria: Clinical Experience from a Tertiary Care Institution

Deza, Gustavo; March-Rodríguez, Álvaro; Sánchez, Sílvia; Ribas‐Llauradó, Clara; Soto, Dulce; Pujol, Ramón M.; Gimeno, Ramón; Giménez‐Arnau, Ana

doi:10.1016/j.jaip.2019.01.026

Cited by 30 publications

(41 citation statements)

References 35 publications

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“…(41,42) and low blood basophil counts in patients with chronic urticaria. (43,44) Furthermore, in our study, blood basophil counts were significantly lower in patients with positive ASST and also tended to be correlated with presence of concomitant autoimmune disease and/or AAbs. This correlation has previously been poorly investigated and with controversial results.…”

Section: F O R P U B B L I C a T supporting

confidence: 51%

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria

Montjoye

Darrigade

Giménez‐Arnau

et al. 2021

Eur Ann Allergy Clin Immunol

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Background: Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To investigate possible correlations between clinical and biological markers and their associations with: (i) disease activity; (ii) resistance to H1-antihistamines; (iii) autoimmunity; and (iiii) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods: Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results: C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p<0.0001) and in more active diseases (p=0.033). D-dimer plasma levels were higher in H1antihistamines unresponders (p=0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p=0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p=0.023), in patients with more active disease (p=0.023), with positive ASST (p=0.001), and with autoimmune status (p=0.057). Conversely, under omalizumab, a decrease of CRP (p=0.0038) and D-dimer serum/plasma levels (p=0.0002) and an increase of blood basophil counts (p=0.0023) and total IgE serum levels (p=0.0007) were observed. Conclusions: This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.

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Section: F O R P U B B L I C a T supporting

confidence: 51%

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria

Montjoye

Darrigade

Giménez‐Arnau

et al. 2021

Eur Ann Allergy Clin Immunol

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“…In addition, no correlation was found between total IgE levels and baseline basophil FcεRI expression ( r = .081, P = .682). However, when removing one extreme outlier with a total IgE > 5000 kU/L, a moderate correlation between baseline total IgE and baseline basophil FcεRI expression ( r = .4, P = .037) was seen, which was comparable to that mentioned in a recent study …”

Section: Resultssupporting

confidence: 84%

“…However, when removing one extreme outlier with a total IgE > 5000 kU/L, a moderate correlation between baseline total IgE and baseline basophil FcεRI expression (r = .4, P = .037) was seen, which was comparable to that mentioned in a recent study. 28…”

Section: Fcεri Expression On Basophils Pdcs and MDC Cd1cs Decreasementioning

confidence: 99%

Response of FcεRI‐bearing leucocytes to omalizumab in chronic spontaneous urticaria

Aghdam

Knol

Elzen

et al. 2020

Clin Experimental Allergy

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Background The pathogenesis of chronic spontaneous urticaria (CSU) and the mechanism of action of omalizumab in CSU remain unclear. Objective In this study, we assessed the responsiveness and FcεRI expression of various subsets of leucocytes in patients with CSU treated with omalizumab. Methods In this prospective cohort study, 30 patients were treated with 6 administrations of 300 mg omalizumab every 4 weeks, followed by a follow‐up period of 12 weeks. FcεRI expression and the percentage of basophils, monocytes, and dendritic cell subsets were analysed before and during treatment, and after follow‐up. In addition, anti‐IgE– and C5a‐induced basophil degranulation was measured. The results were correlated with disease activity and response to omalizumab. Results In addition to a rapid and significant reduction in FcεRI on basophils, we demonstrated a reduction in FcεRI on plasmacytoid dendritic cells during omalizumab treatment, which persisted until 3 months after discontinuation. FcεRI expression on basophils and its reduction did not correlate with the treatment response. Omalizumab led to an increased percentage of basophils in blood but not of the other FcεRI‐bearing leucocytes. Basophil responsiveness was differentially affected; anti‐IgE–, but not C5a‐induced basophil degranulation increased during the treatment. Apart from clinical non‐responders showing a stronger increase in anti‐IgE–induced basophil degranulation over a period time, no differences were found in omalizumab responders vs non‐responders. Conclusions/Clinical Relevance FcεRI expression on basophils decreased rapidly, while anti‐IgE–induced degranulation significantly increased due to omalizumab treatment in patients with CSU, persisting at least for 3 months after stopping the treatment. None of the markers were able to predict the effectiveness of treatment. Whether basophils play a role in omalizumab responsiveness in CSU remains unclear.

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“…So far, it has been demonstrated that omalizumab reduces free serum IgE, 17 thereby leading to a reduction of cell-bound IgE and downregulation of cell surface FceRI expression. [18][19][20][21] Furthermore, basophil releasability upon IgE-mediated activation, which is disturbed in a subgroup of CSU patients, 9,22 recovers during omalizumab therapy. 23 In addition, individual immune alterations might contribute to a differentiated therapeutic outcome.…”

Section: Introductionmentioning

confidence: 99%

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

Rauber

Pickert²,

Holiangu³

et al. 2020

Acad Dermatol Venereol

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Background The anti‐IgE antibody omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU) in patients insufficiently responding to antihistamines. However, its mode of action in CSU is not clearly understood. Objectives The aim of this study was to get a better insight in the immune mechanisms involved in clinical improvement of CSU patients treated with omalizumab. Methods Chronic spontaneous urticaria patients (n = 15) were followed for 5 months after initiation of omalizumab treatment. Clinical symptoms were assessed by UCT and CU‐Q2oL. Cell‐bound IgE was quantified on both FcεRI‐ and FcεRII‐expressing cell populations in peripheral blood. In addition, IgE and IgG as well as their receptors were measured on basophils, and basophil activation was assessed with different concentrations of anti‐FcεRI and fMLP. Furthermore, the frequencies of different T‐cell subsets secreting IL‐5, IL‐10, IL‐31 or IFN‐γ were analysed by ELISpot assay. Results Seven patients showed a full, five a partial and three no clinical response to omalizumab. Cell‐bound IgE was reduced on FcεRI‐bearing cells, but not on FcεRII‐expressing cells. Likewise, the expression of FcεRI declined. Basophil activation increased upon FcεRI‐stimulation while their sensitivity was not affected. Both basophil and T‐cell frequencies remained unchanged. However, when comparing the individual response to omalizumab treatment with distinct T‐cell subsets, a significant correlation was found between improved UCT and decreased frequencies of IL‐10‐, IL‐31‐ and IFN‐γ‐secreting T cells. Conclusions We here show that besides addressing IgE‐dependent immune mechanisms, omalizumab treatment of CSU patients has effects on distinct T‐cell subsets, which correlate with clinical improvement.

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Relevance of the Basophil High-Affinity IgE Receptor in Chronic Urticaria: Clinical Experience from a Tertiary Care Institution

Cited by 30 publications

References 35 publications

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria

Response of FcεRI‐bearing leucocytes to omalizumab in chronic spontaneous urticaria

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

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