Total IgE as a Marker for Chronic Spontaneous Urticaria

Altrichter, Sabine; Fok, Jie Shen; Jiao, Qingqing; Kolkhir, Pavel; Pyatilova, Polina; Romero, Sherezade Moñino; Scheffel, Jörg; Siebenhaar, Frank; Steinert, Carolin; Terhorst‐Molawi, Dorothea; Xiang, Yi-Kui; Church, Martin K.; Maurer, Marcus

doi:10.4168/aair.2021.13.2.206

Cited by 69 publications

(76 citation statements)

References 73 publications

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“…In all adult CSU patients, we strongly recommend a) checking for symptoms of autoimmune diseases and screening for IgG anti-TPO with annual reassessment of thyroid function in positive asymptomatic cases; and b) a follow-up on a regular basis of patients with aiCSU, especially female patients with HT and/or a positive family history, to screen for signs and symptoms of other autoimmune diseases. 11 41 Further studies are needed and should use additional markers for aiCSU, for example total IgE 52 or the ratio of IgG anti-TPO to total IgE, a recently reported marker for aiCSU. 4 …”

Section: Discussionmentioning

confidence: 99%

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

Kolkhir

Altrichter

Asero

et al. 2021

Allergy Asthma Immunol Res

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Purpose Patients with chronic spontaneous urticaria (CSU) have an increased risk for comorbid autoimmune diseases. In this retrospective multicenter study of CSU patients, we evaluated clinical and laboratory features of CSU associated with a higher risk of comorbid autoimmune diseases. Methods We analyzed records of CSU patients (n = 1,199) for a history or presence of autoimmune diseases. Patients were diagnosed with type IIb autoimmune CSU (aiCSU) if all 3 tests were positive: autologous serum skin test (ASST), basophil histamine release assay (BHRA) and/or basophil activation test (BAT), and IgG autoantibodies against FcεRIα/IgE detected by immunoassay. Results Twenty-eight percent of CSU patients had at least 1 autoimmune disease. The most prevalent autoimmune diseases were Hashimoto's thyroiditis (HT) (≥ 21%) and vitiligo (2%). Two percent of CSU patients had ≥ 2 autoimmune diseases, most frequently HT plus vitiligo. Comorbid autoimmune diseases, in patients with CSU, were associated with female sex, a family history of autoimmune diseases, and higher rates of hypothyroidism and hyperthyroidism ( P < 0.001). Presence of autoimmune diseases was linked to aiCSU ( P = 0.02). The risks of having autoimmune diseases were 1.7, 2.9 and 3.3 times higher for CSU patients with a positive ASST, BHRA and BAT, respectively. In CSU patients, markers for autoimmune diseases, antinuclear antibodies and/or IgG anti-thyroid antibodies were associated with non-response to omalizumab treatment ( P = 0.013). Conclusions In CSU, autoimmune diseases are common and linked to type IIb autoimmune CSU. Our results suggest that physicians assess and monitor all adult patients with CSU for signs and symptoms of common autoimmune diseases, especially HT and vitiligo.

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Section: Discussionmentioning

confidence: 99%

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

Kolkhir

Altrichter

Asero

et al. 2021

Allergy Asthma Immunol Res

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“…Our findings indicate that these phenotype-specific DMPs or DMGs will become potential biomarkers of the corresponding CSU subtypes. According to the study of Altrichter et al, low tIgE may suggest type IIb autoimmune CSU, poor response to treatment with omalizumab, and a better chance to benefit from cyclosporine treatment (37). The study of Kolkhir et al showed that 28% of CSU patients had at least one autoimmune disease and the most prevalent comorbid autoimmune disease was Hashimoto's thyroiditis (21%) (38).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria

Zhang²,

Yang³

et al. 2021

Front. Immunol.

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BackgroundChronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU.Patients and MethodsGenome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases.ResultsA total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δβ| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δβ| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively.ConclusionThis study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU.

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“…Elevated levels of serum IgE were often found not only in atopic patients but also in chronic urticaria. Omalizumab is now regarded as the first-line drug for antihistamine-resistant chronic urticaria [14][15][16]. Omalizumab was found to be more effective for chronic urticaria patients with higher serum concentrations of IgE, whereas cyclosporine was efficacious for those with lower IgE [15].…”

Section: Roles Of Ige In Urticariamentioning

confidence: 99%

“…Omalizumab is now regarded as the first-line drug for antihistamine-resistant chronic urticaria [14][15][16]. Omalizumab was found to be more effective for chronic urticaria patients with higher serum concentrations of IgE, whereas cyclosporine was efficacious for those with lower IgE [15]. The pathological roles of IgE and FcεRI in chronic urticaria are classified into type I and type IIb; in the type I group, autoreactive IgEs, which could recognize autoantigens, such as thyroid peroxidase, tissue factor, thyroglobulin, double strand DNA, and IL-24, are produced [17][18][19][20], and in the type IIb group, IgM or IgG that could recognize IgE or FcεRI is produced.…”

Section: Roles Of Ige In Urticariamentioning

confidence: 99%

Roles of IgE and Histamine in Mast Cell Maturation

Tanaka

Furuta

2021

Cells

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Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fce receptor I (FceRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.

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Total IgE as a Marker for Chronic Spontaneous Urticaria

Cited by 69 publications

References 73 publications

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria

Roles of IgE and Histamine in Mast Cell Maturation

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