Differentiation between control subjects and patients with chronic spontaneous urticaria based on the ability of anti-IgE autoantibodies (AAbs) to induce FcεRI crosslinking, as compared to anti-FcεRIα AAbs

Izaki, Satoshi; Toyoshima, Shota; Endo, Takahiro; Kanegae, Kazuko; Nunomura, Satoshi; Kashiwakura, Jun‐ichi; Sasaki-Sakamoto, Tomomi; Nakamura, Ryosuke; Akiyama, Hirotada; Ra, Chisei; Hayama, Koremasa; Terada, Tadashi; Okayama, Yoshimichi

doi:10.1016/j.alit.2019.01.003

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…In view of these shortcomings with acid-based stripping of IgE, we believe that this method could not be used for deciphering the functions of anti-IgE autoantibodies that are found in the healthy individuals and in several pathologies including atopic and non-atopic asthma, chronic spontaneous urticaria, atopic dermatitis and others [13][14][15]18,[44][45][46][47][48][49][50]. Previous reports have used myeloma IgE-coupled cyanogen bromide (CNBr)-activated Sepharose 4B columns to deplete anti-IgE autoantibodies from the serum of the patients or from the therapeutic normal IgG [14,18,19].…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have used myeloma IgE-coupled cyanogen bromide (CNBr)-activated Sepharose 4B columns to deplete anti-IgE autoantibodies from the serum of the patients or from the therapeutic normal IgG [14,18,19]. In addition, micro-well coating of human myeloma IgE protein followed by incubation with purified IgG to remove anti-IgE reactivity has also been attempted [47]. As stripping of IgE on the surface of basophils would lead to an equivalent of 'IgE knock-out' basophil model, we anticipated such IgE-deficient basophils would provide convincing evidence that anti-IgE IgG autoantibodies induce human basophil activation.…”

Section: Discussionmentioning

confidence: 99%

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Acid Stripping of Surface IgE Antibodies Bound to FcεRI Is Unsuitable for the Functional Assays That Require Long-Term Culture of Basophils and Entire Removal of Surface IgE

Galeotti

Karnam

Das

et al. 2020

IJMS

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Basophils are rare granulocytes and dysregulated functions of these cells are associated with several atopic and non-atopic allergic diseases of skin, respiratory system and gastrointestinal tract. Both cytokines and immunoglobulin E (IgE) are implicated in mediating the basophil activation and pathogenesis of these disorders. Several reports have shown that healthy individuals, and patients with allergic disorders display IgG autoantibodies to IgE and hence functional characterization of these anti-IgE IgG autoantibodies is critical. In general, anti-IgE IgG autoantibodies modulate basophil activation irrespective of allergen specificity by interacting with constant domains of IgE. Therefore, an ideal solution to prove the functions of such anti-IgE IgG autoantibodies would be to completely eliminate type I high affinity immunoglobulin E receptor (FcɛRI)-bound IgE from the surface of basophils and to demonstrate in an unequivocal manner the role of anti-IgE IgG autoantibodies. In line with previous reports, our data show that FcɛRI on peripheral blood basophils are almost saturated with IgE. Further, acetic acid buffer (pH 4) efficiently removes these FcɛRI-bound IgE. Although immediately following acetic acid-elution of IgE had no repercussion on the viability of basophils, following 24 h culture with interleukin-3 (IL-3), the viability and yield of basophils were drastically reduced in acid-treated cells and had repercussion on the induction of activation markers. Lactic acid treatment on the other hand though had no adverse effects on the viability of basophils and IL-3-induced activation, it removed only a small fraction of the cell surface bound IgE. Thus, our results show that acid buffers could be used for the elution of FcɛRI-bound IgE on the basophil surface for the biochemical characterization of IgE antibodies or for the immediate use of basophils to determine their sensitivity to undergo degranulation by specific allergens. However, these methods are not utile for the functional assays of basophils that require longer duration of culture and entire removal of surface IgE to validate the role of anti-IgE IgG autoantibodies that interact with FcɛRI-bound IgE irrespective of allergen specificity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acid Stripping of Surface IgE Antibodies Bound to FcεRI Is Unsuitable for the Functional Assays That Require Long-Term Culture of Basophils and Entire Removal of Surface IgE

Galeotti

Karnam

Das

et al. 2020

IJMS

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“…IgE and IgG antibodies against thyroid peroxidase (TPO) were also found in a subgroup of CSU patients and were shown to activate mast cells ( 17 – 20 ). Subsequent studies have shown that IgG autoantibodies binding to FcϵRI/IgE result in mast cell degranulation and basophil activation to release a series of inflammatory mediators, finally leading to vasodilation in the lesional skin of CSU ( 14 , 21 ) ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Zhou

et al. 2022

Front. Immunol.

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Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of spontaneous wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis of CSU is the activation of mast cells, T cells, eosinophils, and other immune cells infiltrating around the small venules of the lesion. Increased vascular permeability, vasodilatation, and recruitment of inflammatory cells directly depend on mast cell mediators’ release. Complex regulatory systems tightly influence the critical roles of mast cells in the local microenvironment. The bias toward Th2 inflammation and autoantibodies derived from B cells, histamine expressed by basophils, and initiation of the extrinsic coagulation pathway by eosinophils or monocytes exerts powerful modulatory influences on mast cells. Cell-to-cell interactions between mast cells and eosinophils/T cells also are regulators of their function and may involve CSU’s pathomechanism. This review summarizes up-to-date knowledge regarding the crosstalk between mast cells and other immune cells, providing the impetus to develop new research concepts and treatment strategies for CSU.

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“…These laborious procedures are unsuitable for screening purposes and have limited utility for determining autoAbs titers. Many groups of researchers ever developed in-house ELISA, and these results revealed the presence of IgG anti-FcεR1α autoAbs [15][16][17]. However, how to earn and apply cut-off points was never clearly demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of an In-House ELISA to Detect Anti-FcεR1α IgG Autoantibodies in Chronic Spontaneous Urticaria Patients

Sripatumtong

Tansit

Tuchinda

et al. 2022

Journal of Immunology Research

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Background. Association between chronic spontaneous urticaria (CSU) and autoimmunity has been well documented. Autologous serum skin testing could support the autoimmune etiology of CSU, whereas it is difficult to interpret and could not be performed on antihistamine omitted patients. It was found that immunoglobulin G (IgG) autoantibodies (autoAbs) against high-affinity IgE receptor (FcεR1) were suggested as a potential trigger in the pathogenesis of CSU. Although many ELISA protocols have been developed to detect these autoAbs, they lacked validation or a reliable cut-off point. We, therefore, aimed to develop a validated ELISA with a reliable cut-off point to quantitate IgG anti-FcεR1α autoAbs for CSU. Methods. We developed an in-house ELISA to quantitate IgG anti-FcεR1α autoAbs. Sera from 233 CSU patients and 25 healthy people were used to test with ELISA. The cut-off point was obtained from the results subjected to analyze with receiver operating characteristic (ROC) analysis. ELISA was validated with 116 CSU patients and 150 healthy donors. Results. ELISA revealed that healthy people had a basal level of IgG anti-FcεR1α autoAbs, whereas their levels were significantly lower than autoAbs levels in CSU patients. ROC analysis of ELISA determined the cut-off point at 936.7 ng/ml. Our ELISA was validated and provided excellent sensitivity and specificity at 98.28% and 92.67%, respectively. Conclusion. Our ELISA could detect significant levels of IgG anti-FcεR1α autoAbs in CSU, supporting that these autoAbs were associated with CSU etiology. Our validated ELISA with the reliable cut-off point provided excellent accuracy at 95.11% (98.28% sensitivity and 92.67% specificity). Our ELISA could be an alternative test benefit for the patient who is unable to omit antihistamine treatment.

show abstract

Differentiation between control subjects and patients with chronic spontaneous urticaria based on the ability of anti-IgE autoantibodies (AAbs) to induce FcεRI crosslinking, as compared to anti-FcεRIα AAbs

Cited by 13 publications

References 46 publications

Acid Stripping of Surface IgE Antibodies Bound to FcεRI Is Unsuitable for the Functional Assays That Require Long-Term Culture of Basophils and Entire Removal of Surface IgE

Acid Stripping of Surface IgE Antibodies Bound to FcεRI Is Unsuitable for the Functional Assays That Require Long-Term Culture of Basophils and Entire Removal of Surface IgE

The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Development and Evaluation of an In-House ELISA to Detect Anti-FcεR1α IgG Autoantibodies in Chronic Spontaneous Urticaria Patients

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