Abstract
BackgroundChronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.MethodsWe developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences.Principal FindingsCsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off ( = 5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPOlow ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86–5.44, = comparable to healthy controls) and 2) IgE-anti-TPOhigh ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.ConclusionOur findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.
Highlights
Urticaria is a common condition characterized by itchy wheal and flare type skin reactions and/or angioedema [1]
Our findings show that a sizeable subgroup of Chronic spontaneous urticaria (csU) patients expresses IgE antibodies against thyroid peroxidase
We have developed an ELISA-based detection assay for IgE antibodies to thyroid peroxidase (TPO) and we have tested csU patients and healthy subjects for the presence of these IgE autoantibodies to TPO (IgE-anti-TPO)
Summary
Urticaria is a common condition characterized by itchy wheal and flare type skin reactions (hives) and/or angioedema [1]. These symptoms are brought about by activated skin mast cells and their subsequent release of histamine and other proinflammatory mediators [2]. IU/ml) as compared to only 13% of healthy control subjects [3] This raises the possibility that in csU mast cells may be activated by allergens that engage specific IgE antibodies bound to their high affinity IgE receptor, FcepsilonRI. Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation
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