Natural anti-FcεRIα autoantibodies isolated from healthy donors and chronic idiopathic urticaria patients reveal a restricted repertoire and autoreactivity on human basophils

Miescher, Sylvia; Horn, Michael P.; Pachlopnik, Jana M.; Baldi, Lucia; Vogel, Monique; Stadler, Beda M.

doi:10.3233/hab-2001-103-404

Cited by 25 publications

(25 citation statements)

References 18 publications

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“…In the other non-CIU skin diseases, the predominant isotypes were IgG 2 or IgG 4 . It has also been reported that antiFcεRIα autoantibodies are part of the naturally occurring repertoire of the immune system [20].…”

Section: Role Of Serologic Factors: Evidence For and Against A Pathogmentioning

confidence: 99%

Basophils and mast cells in chronic idiopathic urticaria

Vonakis

Saini

2005

Curr Allergy Asthma Rep

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Chronic idiopathic urticaria (CIU) is diagnosed in patients when urticarial eruptions recur for more than 6 weeks, and no specific cause is determined. Given that urticaria resembles the lesions induced by injection of histamine or allergen into the skin, a role for mast cells or basophils has been proposed in the generation of localized urticarial lesions. However, currently, the exact mechanisms governing regional mast cell or basophil activation are unknown. In the past decade, there has been mounting interest in viewing CIU as an autoimmune disease, given the presence of circulating autoantibodies to IgE or the alpha subunit of the high-affinity IgE receptor (FceRI) in a subset of patients. In this review, we propose that in addition to autoantibodies, specific differences in the expression of FceRI-signaling molecules in the basophils or mast cells of CIU patients may contribute to the generation of urticarial eruptions.

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Section: Role Of Serologic Factors: Evidence For and Against A Pathogmentioning

confidence: 99%

Basophils and mast cells in chronic idiopathic urticaria

Vonakis

Saini

2005

Curr Allergy Asthma Rep

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“…The H chains were cut with XhoI and SpeI, and L chains were cut with XbaI and SacI (Roche). The resulting fragments were separately pooled and sequentially cloned into pMVS (12), a vector based on pComb3H that allows the expression of Fab on the surface of the filamentous phage M13 (25). Ligation, transformation of Escherichia coli XL-1 Blue strain, and production of phage particles were conducted as described previously (26 -28) (the phagemid DNA was directly amplified in bacteria without performing affinity maturation in vitro).…”

Section: Setmentioning

confidence: 99%

“…Phages were titrated and diluted (ϳ10 12 CFU/ml in PBS with 2% FCS and 0.05% Tween 20). To test the specificity of the phages, ELISA plates (same as for biopanning) were coated with Fc⑀RI␣-HSA-Fc⑀RI␣ (5 g/ml in 0.05 M NaHCO 3 (pH 9.6), 50 l/well, 4°C, overnight) or, for controls, with equimolar HSA or 10 g/ml anti-human Fab (The Binding Site; product PC005).…”

Section: Phage Elisa and Phage Inhibition Assaymentioning

confidence: 99%

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A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the FcεRIα

Bobrzynski

Fux

Vogel

et al. 2005

The Journal of Immunology

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Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the α domain of the high-affinity IgE receptor (FcεRIα) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcεRIα Abs are present in the germline repertoire, we constructed a phage Fab display library from human cord blood, which represents the naive immune repertoire before exposure to exogenous Ags. All isolated clones specific to the FcεRIα had the same sequence. This single IgM Ab, named CBMα8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcεRIα recognized by both CBMα8 and the previously isolated anti-FcεRIα Abs from autoimmune and healthy donors. This common epitope on FcεRIα coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMα8-like specificity, but with a significantly lower affinity in i.v. Ig, a therapeutic multidonor IgG preparation. We propose a hypothesis of escape mutants, whereby the resulting lower affinity IgG anti-FcεRIα Abs are rendered less likely to compete with IgE for binding to FcεRIα.

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“…2 In the past decade, considerable efforts have been made to identify competitors to specifically inhibit the interaction between IgE and FcεRI. 3 These include comprehensive screening of engineered proteins, peptides and nucleic acids, [4][5][6] creation of autoantibody responses against the IgE receptor binding site 7,8 or generation of anti-IgE antibodies. 9 Highly specific anti-IgE antibodies that are capable of selectively blocking the IgE-FcεRI interaction have proven to be effective agents for treating allergic illnesses.…”

Section: Introductionmentioning

confidence: 99%