Positive Autologous Serum Skin Test Research Articles

The efficacy of autologous serum therapy in chronic spontaneous urticaria: A systematic literature review and meta-analysis

Chronic spontaneous urticaria (CSU) is an autoimmune disease characterised by urtica lesions and/or angioedema accompanying an itching sensation, recurring for at least six weeks without any specific trigger. Autologous serum therapy (AST) is an adjuvant therapy for CSU that is resistant to H1 antihistamines. This therapy is an economical option in developing countries. There were a few studies discussing the role of AST in CSU. This systematic review and meta-analysis were conducted to evaluate the efficacy of AST based on urticaria activity scores (UAS or UAS7) and urticaria total severity scores (TSS) so that clinicians can consider them. Data were searched systematically in Cochrane, PubMed, Google Scholar, Willey, and EMBASE from 2000 to March 2023. Data analysis using Excel 2010 (Microsoft Corp) and MedCalc version 20.218. There were 14 studies: 4 randomised controlled trials (RCT), 9 prospective, and 1 cross-sectional. The average improvement in UAS and TSS scores at the end of therapy was 42.24% and 41.24%. Results of subgroup analysis of AST administration in the group autologous serum skin test (ASST) positive and ASST negative based on the end of therapy UAS score (p=0.18). Results of subgroup analysis of AST administration in the positive ASST and negative ASST groups based on the TSS score at the end of therapy (p=<0.001). Results of subgroup analysis of AST administration versus placebo based on TSS score (p=0.861). Based on subgroup analysis, autologous serum therapy improves TSS scores in CSU patients (ASST positive). However, AST is not significantly different from placebo.

The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study.

Background. Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. Methods. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. Results. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. Conclusions. Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.

Exploring the Autoimmune Pathogenesis in Severe Asthma

Introduction: Severe asthma has a poor response to hormone therapy and a poor level of control, so the discovery of new pathogenetic mechanisms is important for diagnosing and treating severe asthma. IL-35 may play a protective role in autoimmune diseases by directly or indirectly inhibiting the secretion of IL-17, which is an important proinflammatory factor involved in the occurrence and development of autoimmune diseases. The autologous serum skin test (ASST) is a good sensitivity and specificity screening test for autoimmune functional autoantibodies. We compared the levels of IL-35 and IL-17 in serum samples, the positive rate of ASST, the level of exhaled nitric oxide (FeNO), and the atopic constitution in patients with severe asthma to those with mild-to-moderate asthma so as to explore the possible autoimmune pathogenesis of severe asthma. Methods: Patients with mild-to-moderate and severe asthma were enrolled. Their age, gender, smoking history, family history of asthma, history of allergic rhinitis, positive allergen results, serum total IgE (TlgE), allergen-specific IgE (slgE), routine blood, ASST results, and FeNO test results were compared and analyzed. The IL-35 and IL-17 levels in serum samples from both groups were measured by enzyme-linked immunosorbent assay for comparison and analysis. The SPSS 22.0 software package was used for statistical analysis. Results: A total of 50 patients with mild-to-moderate asthma and 31 patients with severe asthma were included in this study. The proportion of patients with a history of smoking and a family history of asthma was significantly higher in the severe asthma group compared to the mild-to-moderate asthma group (all p < 0.05); the number of positive allergen tests was significantly lower in patients with severe asthma compared to those with mild-to-moderate asthma (p < 0.001). The rate of positive ASST was significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05). Serum IL-17 levels were significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05), but serum IL-35 level between the two group was not significantly different (p = 0.113). ASST-positive patients had a statistically significant increase in the risk of developing severe asthma, while patients with allergen positive were less likely to develop severe asthma (positive ASST: OR = 5.277, p = 0.024; allergen positivity: OR = 0.123, p = 0.001). Conclusions: IL-35 has a weaker inhibitory effect on high IL-17 expression in patients with severe asthma, and the rate of positive ASST was significantly higher in patients with severe asthma, which all suggested the possibility of autoimmune pathogenesis in patients with severe asthma.

Biomarkers of Autoimmune Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers. Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.

Autoimmune Diseases and Low Baseline IgE in Chronic Spontaneous Urticaria: A Clinical and Therapeutic Prospective Analysis in Real-Life Clinical Practice

Autoimmunity contributes to the pathogenesis of chronic spontaneous urticaria (CSU). The subtyping of CSU has revealed an autoimmune form of CSU. Despite autoimmune diseases having been associated with CSU, there are few prospective studies that have evaluated the characteristics and biomarkers of patients with CSU and autoimmune disease in a real-life practice setting. To evaluate the presence of specific biomarkers for the presence of autoimmune disease in CSU and to analyze the clinical and therapeutic features of patients with CSU and autoimmune disease. The clinical, laboratory, and therapeutic features of patients with CSU at a tertiary-level center were prospectively collected. Data obtained were compared in function of the presence/absence of autoimmune disease and typified according to IgE levels. Patients with CSU who had associated autoimmune disease corresponded to middle-aged women with a common pattern of blood test findings: both low baseline IgE and high-affinity receptor of IgE expression, basopenia, eosinopenia, higher baseline erythrocyte sedimentation rate and D-dimer, increased presence of antinuclear antibodies, IgG against thyroid peroxidase, and positive autologous serum skin test result. Total baseline IgE less than or equal to 43.8 IU/mL was both the optimal cutoff to predict autoimmune disease in the CSU cohort and a significant risk factor for the presence of autoimmune disease in the regression analysis. In real-life clinical practice, characteristics of patients with CSU and autoimmune disease share common features with type IIb autoimmune CSU. Total baseline IgE less than or equal to 43.8 IU/mL has been detected as a possible biomarker of autoimmune disease in patients with CSU.

Most Patients With Autoimmune Chronic Spontaneous Urticaria Also Have Autoallergic Urticaria, but Not ViceVersa.

Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell-activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]-anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG-anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE). To investigate the rates of CSU patients with aaCSU and aiCSU. We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]-anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both. Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment. Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology.

Efficacy and Safety of Autologous Serum Therapy in Chronic Spontaneous Urticaria in the Pediatric Population: A Prospective Pilot Study.

Chronic spontaneous urticaria (CSU) in children is mostly spontaneous in onset (57%). Treatment comprises long-term antihistaminic therapy without need for elaborate investigations. A subset of such patients don't respond to conventional treatment and novel therapies to help reduce pill burden is the need of the hour. To determine the efficacy and safety of autologous serum therapy (AST) in pediatric patients with chronic spontaneous urticaria. All pediatric patients, aged between 6-16 years, attended to our OPD from March 2019 to March 2020 were recruited. Clinico-demographic data and baseline investigations of all patients were performed. Two-weekly AST therapy was given for 8 visits with levocetrizine tablet 5mg on an on-demand basis. Urticaria activity score (UAS) sheet was provided to record and return every 2 weeks. Statistical analysis was done using the IBM SPSS 26 software package. Autologous serum skin test (ASST) was positive in 63% patients. Both the ASST positive and ASST negative group showed significant reduction in UAS7 score at week 14 compared to baseline. The reduction in mean UAS7 score was associated with a decreased pill burden and positive response in the patient and physician global assessment scale. No statistically significant difference between the two groups in terms of mean UAS7 reduction was found. This study has explored the efficacy and safety of autologous serum therapy in the pediatric CSU patients. Both ASST positive and ASST negative group respond to AST therapy.

Autologous serum therapy reduces the symptoms and antihistamine burden in patients with chronic urticaria.

Autologous serum therapy (AST) is considered a potentially curative therapeutic option in the treatment of chronic urticaria, especially in the autoreactive type. To determine the ratio of patients with a positive autologous serum skin test (ASST) in chronic urticaria and the efficacy of AST. A total of 77 (29 male and 48 female) patients with chronic urticaria were enrolled in the study. The autologous serum skin test (ASST) was performed for all patients and the patients were classified into two groups: ASST positive and ASST negative. Intramuscular injection of AST was administered and the total severity score (TSS) of the urticaria was calculated weekly for ten weeks. The TSS was calculated for another ten weeks without AST. There were 34 patients (11 men and 23 women) in the positive group and 43 (18 men and 25 women) in the negative group. Reduction of symptoms of urticaria begins in the fourth week of the study in both groups. At week 20, 21 (61.7%) patients of the ASST (+) group and 12 (27.2%) patients of the ASST (-) group showed complete clearance. The use of antihistamines decreased from 100% at baseline in both groups to 8.82% and 25.58% in the ASST (+) and ASST (-) groups, respectively, at the end of the study. AST is a low-cost, cost-effective and potentially curative treatment with no adverse effects in these patients. It can reduce the burden of antihistamines.

Chronic Spontaneous Urticaria: Clinical Profile, Autologous Serum Skin Test Positivity and Associated Impairment in Quality of Life in Nepalese Patients

Background Chronic Spontaneous Urticaria is considered to be an autoimmune phenomenon in half of the total cases. Autologous serum skin test is a simple screening test for the presence of auto-antibodies in chronic urticaria. Significant impairment in quality of life have been observed in autologous serum skin test positive cases. There are limited literatures on chronic spontaneous urticaria, autologous serum skin test and associated Dermatology Life Quality Index in Nepal till date.&#x0D; Objective To find the proportion of autologous serum skin test positive cases in chronic urticaria and impairment in quality of life in such patients.&#x0D; Method This was a retrospective review of outpatient records of patients diagnosed with chronic spontaneous urticaria, from January 2018 to December 2019, from a tertiary care hospital in Kathmandu, Nepal. Details of the patients, autologous serum skin test and dermatology life quality index scores were analyzed and presented.&#x0D; Result Among the total 114 cases positive autologous serum skin test was seen in 48.2% of cases. The mean total Dermatology Life Quality Index score was 8.06±6.64. A significantly higher quality of life impairment was observed in in patients with positive autologous serum skin test as compared to the negative ones. The odds of finding a positive autologous serum skin test in patients with angioedema was 2.1, however the difference was not statistically significant.&#x0D; Conclusion Chronic spontaneous urticaria was more common in females as compared to males. A positive autologous serum skin test was present in half of the patients which was in turn associated with a greater impairment of quality of life.

Prevalence, Clinical Manifestations, Treatment, and Clinical Course of Chronic Urticaria in Elderly: A Systematic Review.

PurposeData specific to the epidemiology, clinical features, and management of chronic urticaria (CU) in the geriatric population remain limited and not well understood. We aim to systematically review the prevalence, clinical manifestations, treatment, and clinical course of elderly patients with CU.Patients and methodsOriginal articles that included data of elderly (aged >60 years) with CU that were published until February 2021 were searched in PubMed, Scopus, and Embase using predfefined search terms. Related articles were evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.ResultsAmong the included 85 studies and 1,112,066 elderly CU patients, most (57.4%) were women. The prevalence of elderly CU in the general population ranged from 0.2–2.8%, and from 0.7–33.3% among all CU patients. Compared to adult CU, elderly CU patients had a higher percentage of wheal alone (73.9%), and lower rate of positive autologous serum skin test and atopy. Gastrointestinal diseases were the most common comorbidity (71.9%), and there was a high rate of malignancies and autoimmune diseases. Second generation H1-antihistamines were commonly used, and achievement of complete control was most often reported. Omalizumab was prescribed in 59 refractory patients, and a significant response to treatment was reported in most patients. The treatment of comorbidities also yielded significant improvement in CU.ConclusionElderly CU was found to be different from adult CU in both clinical and laboratory aspects. H1- antihistamines are effective as first-line therapy with minimal side-effects at licensed doses. Treatment of secondary causes is important since the elderly usually have age-related comorbidities.

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

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.

Comparison of chronic idiopathic urticaria patients with positive and negative autologous serum skin test

&lt;p&gt;&lt;strong&gt;Background&lt;/strong&gt;: Chronic urticaria, with or without angioedema, has been defined as daily or almost daily symptoms and signs recurring for more than six weeks. Chronic urticaria has an idiopathic etiology in majority. This is called as chronic idiopathic urticaria (CIU) or chronic spontaneous urticaria (CSU). Aim and objectives were to compare the clinical features in CIU patients with a positive autologous serum skin test (ASST) and negative ASST.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods&lt;/strong&gt;: Fifty clinically diagnosed patients of CIU attending the department of DVL OPD at tertiary care teaching hospital, were enrolled based on the inclusion and exclusion criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; ASST was positive in 48% (24/50) of patients with CSU. In study of 50 patients, 66% were females and 34% were males. The mean age of patients was 36.8 years. The disease's median duration was 10 months and 11 months in ASST positive and ASST negative groups respectively. Of the 50 patients, 20 patients showed a positive response to the test for simple dermographism, of which 13 were ASST positive. Of the 50 patients, 8 patients gave a history of atopy, of which 5 were in the ASST positive group, 3 were in ASST negative group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions&lt;/strong&gt;: In the present study ASST was positive in 48% of patients with CIU. Majority of ASST positive patients had almost daily attacks. ASST positive patients had a longer duration of persistence of wheals. ASST is a fairly good indicator of autoimmune etiology for chronic urticaria.&lt;/p&gt;

Chronic spontaneous urticaria after BNT162b2 mRNA (Pfizer-BioNTech) vaccination against SARS-CoV-2.

Background: The factors that trigger and exacerbate chronic spontaneous urticaria (CSU) are well known, but it is not unclear whether messenger RNA (mRNA) vaccination against severe acute respiratory syndrome coronavirus 2 can trigger new cases of CSU or a relapse of CSU after long-term remission. Objective: To study the clinical cases of patients with new-onset CSU and CSU in remission who relapsed within 3 months after BNT162b2 mRNA vaccination. Methods: All patients with a CSU diagnosis within 12 weeks of BNT162b2 mRNA vaccination were retrospectively identified and included in the new-onset CSU and the relapsed CSU groups. The first control group (CSU control group) retrospectively consisted of patients diagnosed with CSU in complete clinical remission for ≥ 6 months, with no CSU relapse after vaccination. The second control group (healthy control group) consisted of subjects who were fully vaccinated and without CSU, matched 1:2 for age and sex with patients with CSU. Results: Twenty-seven patients were included in the relapsed CSU group, 32 patients in the new-onset CSU group, 179 patients in the CSU control group, and 476 subjects in the healthy control group. The relapsed CSU and new-onset CSU groups had more allergic comorbidities overall (19 [70.4%] and 13 [40.6%], respectively) than the CSU control group and the healthy control group (50 [27.9%] and 110 [23.1%], respectively; p < 0.001). Multiple logistic regression analysis showed that a positive autologous serum skin test result, overall allergic comorbidities, and basopenia were positively associated with the probability of CSU relapse within 3 months after BNT162b2 mRNA vaccination (odds ratio [OR] 5.54 [95% confidence interval {CI}, 2.36-13.02], p < 0.001); OR 6.13 [95% CI, 2.52-14.89], p = 0.001; and OR 2.81 [95% CI, 1.17-6.72, p = 0.020, respectively). Conclusion: It is possible that BNT162b2 mRNA vaccination serves as a provoking and/or relapsing factor of CSU in individuals with allergic diseases and/or predisposed autoimmunity.

Autoimmune Chronic Spontaneous Urticaria Detection with IgG Anti-TPO and Total IgE

Autoimmune chronic spontaneous urticaria (aiCSU) comes with high disease activity and poor response to treatment. Recently, elevated levels of IgG anti-thyroid peroxidase (aTPO) and low levels of total IgE were reported to be common in aiCSU. To investigate how high aTPO and low IgE individually and combined are linked to features of aiCSU, including treatment responses. We analyzed records of patients with CSU from 2 independent cohorts (n= 1120) for demographic, clinical, and laboratory parameters and treatment responses. Total IgE and aTPO were measured, and 4 markers of aiCSU were analyzed: autologous serum skin test, basophil activation test (BAT), and blood eosinophil and basophil counts. Cutoff values were greater than or equal to 34 kU/L (high aTPO) and less than 40 IU/mL (low total IgE). One of 10 patients with CSU had both high aTPO and low IgE (aTPO↑IgE↓, 11%, n= 123). aTPO↑IgE↓ was linked to higher age at CSU onset, being female, angioedema, and shorter CSU duration. aTPO↑IgE↓ was associated with markers of aiCSU, that is, BAT and autologous serum skin test positivity, basopenia, and eosinopenia (P < .01 for all). Almost half the patients with aTPO↑IgE↓ (44%, 19 of 43) had a positive BAT result, the best single marker for aiCSU, versus 12% (43 of 344) of patients without aTPO↑IgE↓ (P < .001). Relative risk of showing BAT positivity for a patient with aTPO↑IgE↓ is 3.636 (95% CI, 2.382-5.551). Patients with aTPO↑IgE↓ showed low response rates to antihistamine treatment as compared with patients without aTPO↑IgE↓ (30% vs 47%; P= .01). Our findings suggest that aTPO↑IgE↓ is a useful diagnostic marker for aiCSU in everyday clinical practice.

Correlation of clinical features with positive autologous serum skin test in Urticaria

Autologous serum skin test (ASST) is the simplest and the best in vivo clinical test for the detection of basophil histamine- releasing activity. In India, ASST positivity was found to be 26.67% in chronic Urticaria. The details enquired from the patients include duration of disease, duration of individual wheals, frequency of attacks, distribution of wheals, associated systemic symptoms, provoking physical factors, food and drug intolerance, seasonal variation, associated angioedema. Out of total 60 patients, 38 patients gave history of exacerbation of symptoms during evening time. But there was no statistical correlation with ASST positivity. Out of total 60 patients 25 patients were found to have increased serum IgE values, of which 17 (68%) were ASST positive, found to be statistically significant.

Low frequency of CD4+CD25highFOXP3+ T regulatory cells in Egyptian patients with chronic spontaneous urticaria

Chronic urticaria is a prevalent disabling dermatological disease. About 90%, are considered idiopathic and referred to as chronic spontaneous urticaria (CSU), and nearly half of them are likely to have autoimmune mechanisms. Regulatory T cells play a substantial role to prevent autoimmune diseases. Subsets of Tregs expressing the CD4+CD25high and forkhead-box-P3 (FOXP3) transcription factor, crucial for their development and function, are best characterized in maintenance of self-tolerance. The objective of this study was the analysis of peripheral CD4+CD25highFOXP3+(T regs) frequency in chronic spontaneous urticaria; and its possible association with autologous serum skin test (ASST). Fifty chronic spontaneous urticaria patients (25 with positive ASST and 25 with negative ASST) and 20 healthy controls were enrolled in this study. The frequency of CD4+CD25highFOXP3+ (T regs) was analyzed by flow cytometry. A Significant decrease in peripheral blood CD4+CD25highFOXP3+ T regs% was detected in CSU patients in comparison to healthy individuals (median [IQR], 1.47% [0.71-3.12] vs 1.79% [1.15-4.00]; P = 0.05). When ASST positive patients were compared with ASST negative patients, no significant difference was found in percentage of T regs, (P=0.112). In conclusion our data provided further insights into CSU pathogenesis. Reduced frequency of CD4+CD25highFOXP3+(Tregs) in patients with urticaria, support the notion that CSU is an immune mediated disease and may help researchers to develop a novel immunotherapy strategy.

Serum Human β-Defensin 2 Is Increased in Angioedema Accompanying Chronic Spontaneous Urticaria

Introduction: Chronic spontaneous urticaria (CSU) is a common cutaneous disease caused by mast-cell degranulation. Human β-defensin 2 (HBD2) is a well-known antimicrobial peptide that is also a pruritogen inducing vascular permeability via non-IgE-mediated mast-cell degranulation. Objective: We investigated the associations between serum HBD2 levels and the clinical characteristics of CSU patients. Methods: Serum samples from 124 CSU patients and 56 healthy controls were screened for the levels of HBD2 and translationally controlled tumor protein (TCTP)_ by using ELISA. The urticaria activity score over 7 days (UAS7) was used to measure disease activity in CSU patients. Accompanying angioedema was self-reported. Results: Serum HBD2 levels were higher in the CSU group than in healthy subjects (median [interquartile range], 84.1 [43.5, 142.5] vs. 59.5 [26.7, 121.5], p = 0.034). In CSU patients, serum HBD2 level was negatively correlated with the peripheral basophil percentages (Spearman’s rho = −0.229, p = 0.01) and vitamin D levels (−0.262, p = 0.02), but positively correlated with TCTP levels (0.252, p = 0.006). In CSU patients, HBD2 level was higher in those with than without angioedema (101.7 [50.9, 184.2] vs. 66.7 [37.9, 132.0], p = 0.019). It did not differ by aspirin hypersensitivity or atopy status, or autologous serum skin test positivity. Conclusion: A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria.

Background. Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective. To investigate possible correlations between clinical and biological markers and their associations with: 1) disease activity, 2) resistance to H1-antihistamines, 3) autoimmunity and 4) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods. Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results. C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p less-than 0.0001) and in more active diseases (p = 0.033). D-dimer plasma levels were higher in H1-antihistamines unresponders (p = 0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p = 0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p = 0.023), in patients with more active disease (p = 0.023), with positive ASST (p = 0.001), and with autoimmune status (p = 0.057). Conversely, under omalizumab, a decrease of CRP (p = 0.0038) and D-dimer serum/plasma levels (p = 0.0002) and an increase of blood basophil counts (p = 0.0023) and total IgE serum levels (p = 0.0007) were observed. Conclusions. This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.

Utilidad de los estudios en busca de autoinmunidad en pacientes con urticaria crónica espontánea

Chronic spontaneous urticaria (CSU) is a common condition in adults, especially among women; this entity is frequently associated with autoimmune diseases. Our goal is to assess through laboratory studies whether patients with autoimmune CSU presented data. A cross-sectional study of 35 patients was done in the area of Allergy and Immunology at Hospital Juarez de Mexico diagnosed with CSU. We performed the following tests: complete blood count, thyroid antibodies (antiperoxidase and thyroglobulin), antinuclear antibodies, rheumatoid factor, lupus anticoagulant, LE cells Autologous Serum Skin Test (ASST), add (C3 and C4). In addition, we made Helicobacter pylori test, thyroid hormones (T3, T4, TSH) and D-dimer. We evaluated 35 adult patients, 27 female; ASST was positive in 4 patients, negative antinuclear antibodies in all cases, but positive anti thyroid (AAT) antibodies in 4. The LE cell, lupus anticoagulant, complement, dimer D, thyroid and Helicobacter pylori profile were normal or negative and rheumatoid factor was positive in one patient. All AAT-positive patients were women, but 26 of them had negative ASST. The correlation between ASST and AAT was not significant. Most patients were women UCE and only 4 had positive ASST, but this does not correlate with the presence of anti-thyroid antibodies. Most studies were normal, so we suggest not making unnecessary laboratory studies in this disease.

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria.

PurposePatients 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.MethodsWe 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.ResultsTwenty-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).ConclusionsIn 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.