Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

Sauer, Merle; Frischbutter, Stefan; Kolkhir, Pavel; Xiang, Yi-Kui; Siebenhaar, Frank; Altrichter, Sabine; Maurer, Marcus; Metz, Martin; Krause, Karoline

doi:10.3389/fimmu.2021.657211

Cited by 22 publications

(14 citation statements)

References 52 publications

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“…Our findings are consistent with the results of a previous study which has shown that lower tIgE is associated with higher prevalence rates of anti-TPO IgE. 12 The antihistamine-refractory CSU patients with positive anti-TPO IgE can be successfully treated with omalizumab. 16 …”

Section: Discussionsupporting

confidence: 92%

“…In this large-sample-size study, we have confirmed higher prevalence rates of anti-TPO IgE and anti-TG IgE in a Chinese Han CSU population and significant correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG. In line with Sauer et al ’s study, 12 we found that the elevated prevalence rates of anti-TPO IgE were associated with lower tIgE levels. The elevated levels of anti-TG IgE in patients with severe CSU decrease after omalizumab treatment.…”

Section: Discussionsupporting

confidence: 90%

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IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

Zhang

Qiu

et al. 2022

Allergy Asthma Immunol Res

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Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG ( r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG ( r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients ( r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels ( P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

Zhang

Qiu

et al. 2022

Allergy Asthma Immunol Res

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“…According to previous studies ASST is considered as a bedside clinical test which can detect the presence of autoimmunity in patients with CSU. 1,21,23,24 Our results agreed with a study, reported that 56% of CSU patients had negative ASST, and pointed out to lack of functional circulating autoantibodies in these patients. 25 However, since 44% of their patients had positive ASST, they suggested that this observation may indicate the presence of functional circulating autoantibodies and an autoimmune basis for their disease.…”

Section: Discussionsupporting

confidence: 92%

Correlation between regulatory T cells and autologous serum skin test among chronic spontaneous urticaria patients

Mohamed

Taha

Ahmed

et al. 2022

EJI

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Chronic spontaneous urticaria (CSU) is considered as an autoimmune disorder in around 30-50% of cases and referred to as chronic autoimmune urticaria. T regulatory cells (Tregs) may be involved in the pathogenesis of CSU. However, their exact role has not yet been fully defined in those patients. This study aimed to investigate the possible role of Tregs cells subsets in CSU patients. In a case-control study, conducted at dermatology clinics, Suez- Canal University Hospitals, Ismailia, Egypt; 25 CSU patients and 25 apparently healthy control blood donors with matched age and gender were recruited. CSU patients were subjected to history taking, physical examination, assessment of urticaria activity score (UAS) and autologous serum skin test (ASST). Blood samples were obtained from both groups to estimate the number of Tregs cells by flow cytometric analysis. The mean values of CD4+ Fox P3+ and CD4+ FoxP3+ CD25+ Tregs in the study cases were increased significantly compared to the controls (Mean ± SD, ]73.51±26.63[ vs ]4.68±2.98[; P= 0.001 and ]0.97±0.59[ vs ]0.56±0.36 [; P =0.003), respectively. However, the mean values of CD4+ CD25+ Tregs were decreased significantly in CSU patients compared to the controls (0.27±0.38 vs 3.63±1.44, P= 0.001). Mean levels of CD4+CD25+ and CD4+ CD25+ FoxP3+ Tregs cells decreased in positive ASST group in comparison to the ASST negative group, but this decrease did not reach statistical insignificance. In conclusion, our data indicated that CSU was associated with alterations in circulating Tregs cells subsets supporting the autoimmune theory.

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“…The BAT is positive if healthy donor basophils degranulate due to autoantibodies present in the patients’ serum. The BAT was performed as previously described ( 4 ). Briefly, the patient’s serum was thawed and incubated with fresh basophils taken from a healthy donor.…”

Section: Methodsmentioning

confidence: 99%

“…In CSU, total immunoglobulin E (IgE) levels have been found to be elevated in a large proportion of patients (2,3) and it is thought to play an important role in the pathogenesis of CSU. Despite this, there are some patients who present with low or very low levels of total IgE (4,5). These patients are especially difficult to treat and are more often non-responders to treatment with Omalizumab, a therapeutic anti-IgE antibody, than those with normal or elevated total IgE (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria

et al. 2022

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BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.ObjectiveOur aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb.MethodsWe included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.ResultsNo differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients.ConclusionIn total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb.

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Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity

Cited by 22 publications

References 52 publications

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

Correlation between regulatory T cells and autologous serum skin test among chronic spontaneous urticaria patients

STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria

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