Natural anti-FcεRIα autoantibodies may interfere with diagnostic tests for autoimmune urticaria

Pachlopnik, Jana M.; Horn, Michael P.; Fux, Michaela; Dahinden, Markus; Mandallaz, Michèle; Schneeberger, Dominique; Baldi, Lucia; Vogel, Monique; Stadler, Beda M.; Miescher, Sylvia

doi:10.1016/j.jaut.2003.09.007

Cited by 33 publications

(26 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because IVIg contains a pool of IgG Abs from human serum, these anti-Fc⑀RI␣ may have undergone a class switch and may result from an immune response that lowers their affinity. This is also consistent with our previous observations that an anti-Fc⑀RI␣ IgG Ab isolated by phage display from CU patients (UG␣8) appeared to have a lower affinity than the IgM Ab LTM␣15, as judged by functional assays (25). The recognition of Fc⑀RI␣ was not as strong as that by the LTM␣ Abs (UG␣8 used at 100 g/ml gave an OD of 0.5, whereas LTM␣15 at 5 g/ml gave an OD of Ͼ1 in the same ELISA experiment; our unpublished observations).…”

Section: Discussionsupporting

confidence: 93%

“…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%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Setmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…These antibodies, which are primarily IgM, show cross reactivity with tetanus toxoid [39][40][41] and may be functional if basophils that have had IgE removed by lactic acid are used. These investigators have suggested that a state of "conditional autoimmunity" may exist in CU, dermal mast cell activation only occurring if these autoantibodies encounter mast cells devoid of IgE.…”

Section: Diagnosis Of Caumentioning

confidence: 99%

“…It seems reasonable at present to rely on demonstration of histamine release from donor basophils as the benchmark diagnostic test for autoimmune urticaria. [29] dermal mast cells 31/78 (40) RBL=rat basophil leukaemia Fig. 7 The autologous serum skin test (ASST).…”

Section: Diagnosis Of Caumentioning

confidence: 99%

Chronic Urticaria: Recent Advances

Greaves

Tan

2007

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Chronic urticaria is an umbrella term, which encompasses physical urticarias, chronic "idiopathic" urticaria and urticarial vasculitis. It is important to recognize patients with physical urticarias as the investigation and treatment differs in important ways from patients with idiopathic chronic urticaria or urticarial vasculitis. Although relatively uncommon, urticarial vasculitis is an important diagnosis to make and requires histological confirmation by biopsy. Underlying systemic disease and systemic involvement, especially of the kidneys, should be sought. It is now recognized that chronic "idiopathic" urticaria includes a subset with an autoimmune basis caused by circulating autoantibodies against the high affinity IgE receptor (FceR1) and less commonly against IgE. Although the autologous serum skin test has been proven useful in prompting search for and characterization of circulating wheal-producing factors in chronic urticaria, its specificity as a screening test for presence of functional anti-FceR1 is low, and confirmation by demonstration of histamine-releasing activity in the patient's serum must be the benchmark test in establishing this diagnosis. Improved screening tests are being sought; for example, ability of the chronic urticaria patient's serum to evoke expression of CD 203c on donor human basophils is showing some promise. The strong association between autoimmune thyroid disease and autoimmune urticaria is also an area of ongoing research. Drug treatment continues to be centered on the H1 antihistamines, and the newer second-generation compounds appear to be safe and effective even in off-label dosage. Use of systemic steroids should be confined to special circumstances such as tapering regimens for acute flare-ups. Use of leukotriene antagonists is becoming popular, but the evidence for efficacy is conflicting. Cyclosporin is also effective and can be used in selected cases of autoimmune urticaria, and it is also effective in non-autoimmune cases, although less so.

show abstract

“…However, their relevance in the pathogenesis of CU remains controversial. 9 The ASST requires freshly prepared serum samples, and antihistamine treatment has to be stopped before testing. Interpretation is sometimes difficult, especially if a pronounced dermographism is present, with reports on the percentage of positive ASST results in the range of 4% to 76% of all patients with CU tested.…”

mentioning

confidence: 99%

Individual IL-3 priming is crucial for consistent in vitro activation of donor basophils in patients with chronic urticaria

Gentinetta

Pecaric‐Petkovic

Wan

et al. 2011

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Natural anti-FcεRIα autoantibodies may interfere with diagnostic tests for autoimmune urticaria

Cited by 33 publications

References 54 publications

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

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

Chronic Urticaria: Recent Advances

Individual IL-3 priming is crucial for consistent in vitro activation of donor basophils in patients with chronic urticaria

Contact Info

Product

Resources

About