Lupus pathogenesis: role of IgE autoantibodies

Bayry, Jagadeesh

doi:10.1038/cr.2016.12

Cited by 15 publications

(10 citation statements)

References 13 publications

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“…Discovering more biomarkers or autoantibodies will help to distinguish SLE patients more safely and effectively. Recently, the presence of IgE autoantibodies binding to dsDNA has been reported in SLE patients and growing evidence suggests the pathogenic role of IgE in SLE (29,30). Increased serum IgE levels were observed in SLE patients in our experiment (P < 0.05) as displayed in Fig.…”

Section: Discussionsupporting

confidence: 70%

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Establishment of a novel quantum dots‐encoded microbead‐based flow cytometric method for quantification of soluble FcεRIα in serum

Lin

et al. 2017

Cytometry Pt A

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The soluble form of the transmembrane glycoprotein, FcεRIα which corresponds to the high-affinity receptor for IgE, is found in serum. Growing evidence suggests the pathogenic role of IgE and FcεRI in systemic lupus erythematosus (SLE). The goal of this study is to develop a sensitive and standardized cytometric assay for quantification of sFcεRIα. A membrane emulsification technique was utilized to incorporate CuInS /ZnS quantum dots and Fe O nanoparticles into poly (styrene-co-maleic anhydride) microbeads. The beads were then carboxylated and coated with capture antibody monoclonal anti-human FcεRIα. This antibody binds to FcεRIα but does not block the binding of FcεRIα to IgE. After incubation with standards or serum samples, the microbeads were incubated with excessive native human IgE, followed by incubation with Phycoerythrin (PE) conjugated anti-human IgE. The resulting quantum dot microbeads were gated, and sFcεRIα quantification was analyzed based on PE fluorescence intensity. The method exhibited good linearity (R > 0.99), and the limit of detection was established at 0.29 ng/mL with the dynamic range of up to 200 ng/mL. The precision of the assay validated by intra- and inter-assay variability met the acceptance criteria with the mean recovery falling within 80-110% of the theoretical concentration and a corresponding CV < 20%. We tested 149 serum samples which 89 were from SLE patients and 60 were from healthy volunteers. For the first time, we detected an increased sFcεRIα level in the serum of SLE patients, which was confirmed by a commercial ELISA kit. Compared to ELISA, this novel method is more sensitive and efficient. It allows for the simple comparative analysis of sFcεRIα levels in health and disease. © 2017 International Society for Advancement of Cytometry.

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Section: Discussionsupporting

confidence: 70%

“…Recently, the presence of IgE autoantibodies binding to dsDNA has been reported in SLE patients and growing evidence suggests the pathogenic role of IgE in SLE (29,30). It is characterized by autoantibodies to nuclear antigens, particularly double-stranded DNA (dsDNA).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel quantum dots‐encoded microbead‐based flow cytometric method for quantification of soluble FcεRIα in serum

Lin

et al. 2017

Cytometry Pt A

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“…Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs including the skin, joints, the central nervous system and the kidneys 1,2 . It is caused by an aberrant autoimmune response to produce antibodies against self-antigens and these autoantibodies form immune complexes (ICs), which are then deposited into different organs and affect their normal function 3 . SLE is a highly heterogeneous disease in terms of development, presentation, manifestations, and severity; also the incidence and prevalence vary remarkably 4 .…”

Section: Introductionmentioning

confidence: 99%

Integrative transcriptomic analysis of SLE reveals IFN-driven cross-talk between immune cells

Panwar

Schmiedel

Liang

et al. 2020

Preprint

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The systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women and may lead to damage in multiple different organs. The marked heterogeneity in its clinical manifestations is a major obstacle in finding targeted treatments and involvement of multiple immune cell types further increases this complexity. Thus, identifying molecular subtypes that best correlate with disease heterogeneity and severity as well as deducing molecular cross-talk among major immune cell types that lead to disease progression are critical steps in the development of more informed therapies for SLE. Here we profile and analyze gene expression of six major circulating immune cell types from patients with well-characterized SLE (classical monocytes (n=64), T cells (n=24), neutrophils (n=24), B cells (n=20), conventional (n=20) and plasmacytoid (n=22) dendritic cells) and from healthy control subjects. Our results show that the interferon (IFN) response signature was the major molecular feature that classified SLE patients into two distinct groups: IFN-signature negative (IFNneg) and positive (IFNpos). We show that the gene expression signature of IFN response was consistent (i) across all immune cell types, (ii) all single cells profiled from three IFNpos donors using single-cell RNA-seq, and (iii) longitudinal samples of the same patient. For a better understanding of molecular differences of IFNpos versus IFNneg patients, we combined differential gene expression analysis with differential Weighted Gene Co-expression Network Analysis (WGCNA), which revealed a relatively small list of genes from classical monocytes including two known immune modulators, one the target of an approved therapeutic for SLE (TNFSF13B/BAFF: belimumab) and one itself a therapeutic for Rheumatoid Arthritis (IL1RN: anakinra). For a more integrative understanding of the cross-talk among different cell types and to identify potentially novel gene or pathway connections, we also developed a novel gene coexpression analysis method for joint analysis of multiple cell types named integrated WGNCA (iWGCNA). This method revealed an interesting cross-talk between T and B cells highlighted by a significant enrichment in the expression of known markers of T follicular helper cells (Tfh), which also correlate with disease severity in the context of IFNpos patients. Interestingly, higher expression of BAFF from all myeloid cells also shows a strong correlation with enrichment in the expression of genes in T cells that may mark circulating Tfh cells or related memory cell populations. These cell types have been shown to promote B cell class-switching and antibody production, which are well-characterized in SLE patients. In summary, we generated a large-scale gene expression dataset from sorted immune cell populations and present a novel computational approach to analyze such data in an integrative fashion in the context of an autoimmune disease. Our results reveal the power of a hypothesis-free and datadriven approach to discover drug t...

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“…Cross-linking of FcεRI-bound IgE by allergens provide potent signal for the degranulation of basophils and mast cells leading to the release of histamine, lipid mediators such as leukotriene C4, and cytokines like IL-4 [1,2]. IgE antibodies to dsDNA and basophils are also implicated in the pathogenesis of lupus nephritis [10,11]. Therefore, IgE has been explored as one of the therapeutic targets in recent years to treat allergic and inflammatory diseases [12].…”

Section: Introductionmentioning

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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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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Lupus pathogenesis: role of IgE autoantibodies

Cited by 15 publications

References 13 publications

Establishment of a novel quantum dots‐encoded microbead‐based flow cytometric method for quantification of soluble FcεRIα in serum

Establishment of a novel quantum dots‐encoded microbead‐based flow cytometric method for quantification of soluble FcεRIα in serum

Integrative transcriptomic analysis of SLE reveals IFN-driven cross-talk between immune cells

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

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