Autologous Serum Skin Test Response Research Articles

Interleukin-23/ Interleukin -17 Axis in Chronic Spontaneous Urticaria: A Case- Control Study

Background: Chronic Spontaneous Urticaria (CSU) is a common health problem and its clear etiology is not established yet. Several theories have been tried to illustrate its etiology and pathogenesis. Autoantibodies and inflammatory cytokines like IL-23 and IL17 are hypothesized to take part in CSU pathogenesis and outcome. Objectives: To detect serum levels of IL-23 and IL-17A among CSU patients and to determine its correlation with disease severity and its relation to autoreactivity. Methodology: Serum levels of IL-23 and IL-17A were measured in 23 patients with CSU (CSU group) and 23 healthy controls (control group). In CSU group, Weekly Urticaria Activity Score (UAS7) was recorded to assess disease severity. Autologous Serum Skin Test (ASST) was performed to assess autoreactivity. CSU patients᾿ group was subdivided, based on ASST, into positive ASST (ASST+ ) and negative ASST (ASST- ) subgroups. Correlation of serum IL-23 & IL-17A levels, with UAS7 and ASST response were analyzed. Results: CSU group had higher serum IL-17A and IL-23 levels than control group (P=0.000). ASST+ CSU had higher serum IL-17A and IL-23 levels than ASSTones (P=0.000). Additionally, UAS7 was higher in ASST+ subgroup than ASST- subgroup (32+11.7 versus 16.27+ 9.92; P =0.005). There was significant positive correlation between disease severity and serum levels of both IL-17A and IL-23 among CSU patients (r= 0.626 & P= 0.001 and r=0.515 & P= .012, respectively). Conclusion: Increased serum IL-17A and IL-23 levels may constitute two major determinants of CSU pathogenesis and severity.

Association of positive and negative autologous serum skin test responses with clinical features of chronic spontaneous urticaria in Asian patients: A systematic review and meta-analysis.

Previous studies on the correlation between positive autologous serum skin test (ASST) responses and the clinical features of patients with chronic spontaneous urticaria (CSU) have provided conflicting results. To evaluate the significance of ASST responses in CSU, a variety of databases were searched from inception to March 2018 to identify relevant studies on CSU. Data were analyzed with use of the Cochrane Collaboration's Review Manager 5.2. Multiple relevant factors of CSU were evaluated by calculating the weighted mean difference, odds ratio and 95% confidence interval. The results indicated that CSU cases with positive ASST responses had higher urticaria activity scores and higher levels of total serum immunoglobulin E than CSU cases with negative responses in the ASST. In addition, a positive ASST response was more likely to be accompanied with the presence of thyroid autoantibodies and angioedema. An increased prevalence of CSU was identified in females, who were more likely to have a positive response in the ASST. It was also indicated that a greater incidence of positive ASST responses was present in CSU patients as compared with that in healthy controls. No statistically significant differences were obtained between positive and negative ASST responses with regard to age and duration of disease. Based on these results, it was concluded that the ASST provides an effective means of predicting urticaria activity and recurrence in CSU patients.

The role and relationship of the serum D-dimer level and autologous serum skin test response in chronic spontaneous urticaria

Background: The severity of chronic urticaria (CU) may be associated with the D-dimer level, and CU patients often have other autoimmune disorders. The autologous serum skin test (ASST) is believed to identify autoimmune/autoreactive diseases in CU patients. Aim: This study evaluated whether the levels of D-dimer, total immunoglobulin E (IgE), and autoimmune markers, such as antithyroid peroxidase (TPO) and antithyroglobulin (TG), differ between ASST-positive and ASST-negative patients among CU patients. In addition, the study assessed whether these laboratory findings were related to CU severity. Methods: The study enrolled 54 adults with CU (16 ASST positive, 38 ASST negative). D-dimer, total IgE, autoimmune marker (anti-TPO and anti-TG), and thyroid hormone levels and the urticaria activity score (UAS) were measured. Results: The levels of D-dimer, total IgE, anti-TPO, and anti-TG and the thyroid function test result showed no difference between the ASST-positive and ASST-negative groups. The UAS was higher in the ASST-positive group than in the ASST-negative group, but the ASST-positive group showed a better treatment response. The UAS was higher in patients with an elevated D-dimer level than in those with a normal level. Total IgE was related to the UAS in only the ASST-negative group, and anti-TPO and anti-TG levels were not related to the UAS. Conclusions: There were no associations between the ASST response and the D-dimer level, total IgE level, thyroid function test results, and thyroid autoantibody levels. However, our findings suggest that the ASST response, D-dimer level, and total IgE level are potential predictors of CU severity.

A Study on T Regulatory Cells in Patients with Respiratory Allergies in Zagazig University Allergy and Immunology Unit

Background: A positive autologous serum skin test (ASST) reflects the presence of anti-FceRI and/or anti-IgE autoantibodies and used to show autoimmunity in cases with respiratory allergies. Impaired CD4+CD25 high FoxP3+ T regulatory cell activity can cause autoimmune diseases and allergy. Objective: To investigate the association between respiratory allergies and CD4+CD25 high FoxP3+ T regulatory T cell count and re-evaluate the significance of ASST reactivity in respiratory allergy patients and healthy controls. Methodology: 16 patients with persistent asthma, 14 seasonal allergic rhinitis patients and 30 control subjects were included. ASST and measurement of FoxP3+ regulatory T cell count was performed in all subjects. Results: ASST was positive in 18/30 (60%) respiratory allergic patients and none of control subjects. FoxP3+Treg cell count was lower in respiratory allergic patients than control subjects with negative correlation with disease severity. Conclusion: Respiratory allergic patients have lower level of FoxP3+ regulatory T cell than normal individuals. A positive ASST response found in respiratory diseases patients suggests that it may occur as a result of some inflammatory events during the diseases process and could be related to disease activity .

The significance of hypersensitivity to autologous sweat and serum in cholinergic urticaria: cholinergic urticaria may have different subtypes.

The pathogenesis of cholinergic urticaria (ChU) has been unclear except for the involvement of acetylcholine. Attempts to classify ChU according to etiology have rarely been performed. To evaluate the significance of responsiveness to autologous sweat and serum in ChU in relation to their clinical characteristics. This study involved 18 patients diagnosed with ChU between January 2010 and April 2011 in the Catholic Medical Center-St. Paul's Hospital. History taking included symptom duration, association with atopy, decreased sweat secretions, seasonal variation, and response to treatment. Intradermal autologous serum skin test (ASST) and autologous sweat skin test (ASwST) and basophil histamine release test with sweat were done. Sweat hypersensitivity was proven by a positive ASwST and basophil histamine release test in only 37.5% of patients with ChU, and in none of the healthy controls. The weal size of ASwST correlated with percentage basophil histamine release. A positive response to autologous serum was displayed by 38.9% of patients, whereas 10% of healthy controls showed a positive ASST response. Intriguingly, patients with a positive ASwST had a negative ASST, and vice versa. Despite this, there was no difference in the clinical characteristics between positive ASST and positive ASwST groups. The frequency of hypersensitivity to autologous sweat and serum was significantly higher in patients with ChU, compared with healthy controls. This suggests that autoimmunity to an unknown serum factor as well as sweat hypersensitivity may be involved in the pathogenesis of ChU.

Autologous serum skin test response in chronic spontaneous urticaria and respiratory diseases and its relationship with serum interleukin-18 level

Autologous serum skin test (ASST) is mostly used in chronic spontaneous urticaria (CSU) to show autoreactivity. Interleukin-18 (IL-18) has also been shown to be involved in autoimmune conditions. To investigate the role of autoreactivity assessed by ASST in CSU and respiratory diseases and to investigate whether this autoreactive state is related to IL-18 level or other clinical covariates. Fifty-five patients with CSU (mean age: 40.3±12.3years), 70 patients with persistent asthma (mean age: 43.7±9.6years), 21 patients with seasonal allergic rhinitis (SAR) (mean age: 35.5±11.8years) and 20 normal controls (mean age: 37.7±9.8) were included. All subjects underwent a laboratory examination and skin prick test. ASST was performed and serum IL-18 levels were measured in all subjects. Positive response to ASST and serum IL-18 levels were higher in CSU patients than those with respiratory diseases (asthma and SAR) (P=0.034 and 0.002, respectively) and normal controls (P=0.004 and 0.031, respectively). Considering all patients, IL-18 levels were higher in patients with positive ASST (301.8±194.4 vs. 241.8±206.3pg/ml, P=0.036) than ASST negative patients. ASST response was associated with disease severity in CSU (P=0.037) and asthma patients (P=0.001). Multivariate analysis showed that positive response to ASST was significantly associated with diagnosis of CSU (OR: 3.13, 95% CI: 1.25-7.87) and female gender (OR: 3.98, 95% CI: 1.19-13.38). ASST response could be related with activity of the disease. A positive ASST response found in respiratory diseases patients suggests that it may occur as a result of some inflammatory events during the diseases' process.

Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. Evaluation of the surface expression of FcepsilonRIalpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of FcepsilonRIalpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.

Association of insertion/deletion polymorphism of the angiotensin‐converting enzyme gene with angio‐oedema accompanying chronic urticaria but not chronic urticaria without angio‐oedema or the autologous serum skin test response

Chronic urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin-converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme. An increase in substance P levels due to a polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria. Ninety-five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio-oedema. One hundred and sixty-one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction. A statistically significant association was not found between ACE I/D polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio-oedema with regard to angio-oedema-negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03). The results of this study suggest no evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio-oedema in chronic ordinary urticaria.

Detection of basophil-activating IgG autoantibodies in chronic idiopathic urticaria by induction of CD63

Approximately 40% to 50% of patients with chronic idiopathic urticaria (CIU) have functional IgG autoantibodies against FcepsilonRIalpha or IgE, which induce histamine release from basophils and cutaneous mast cells. A positive autologous serum skin test response is believed to reflect the presence of these autoantibodies. We sought to further define the functional properties of and develop a sensitive functional assay for detection of autoantibodies in patients with CIU. Sera from patients with CIU (n=61) and sera from healthy control subjects (n=23) were incubated with donor basophils. Activation of basophils was determined on the basis of CD 63 surface expression, as analyzed on a FACScan flow cytometer. A positive basophil activation test result was found in 51% of patients with CIU, and basophil-activating properties were present in the IgG fractions of sera. When both the in vitro test and the autologous serum skin test were considered, basophil/mast cell-activating autoantibodies were present in 62% of the patients. Patients with a positive basophil activation test result had a significantly higher prevalence of other autoantibodies, had more severe urticaria, and were more likely to have angioedema. The results demonstrate the presence of basophil-activating autoantibodies in about 50% of patients with CIU. The data support the autoimmune cause of the disease and provide a simple test for detection of these autoantibodies.