What Basophil Testing Tells Us About CSU Patients – Results of the CORSA Study

Abstract

Basophil testing is the most effective single approach for diagnosing type-IIb autoimmune chronic spontaneous urticaria (TIIbaiCSU). A positive basophil test has been linked to long disease duration, higher disease activity, a poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib. As of now it is unclear what other features are connected to a positive basophil test in chronic spontaneous urticaria (CSU). We aimed to identify features of basophil test-positive CSU patients. We performed a cross-sectional study of 85 CSU patients. Basophil testing was done with the basophil activation test (BAT) and the basophil histamine release assay (BHRA). Data were analysed using SPSS: Student’s t-test, Chi-square test, Odds Ratio, Spearman’s correlation test. Of 85 CSU patients, 44% and 28% tested positive with the BAT and BHRA, respectively. These patients showed higher disease activity and impact, lower levels of disease control and total serum IgE, as well as higher rates of having a positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms for >5 days/week, and thyroid autoantibodies. The ASST, by itself, was not a good predictor of basophil test results, but it predicted a positive basophil test in up to 100% of cases when combined with angioedema, thyroid autoantibodies or low IgE. In conclusion, a positive basophil test is linked to known features of TIIbaiCSU and novel characteristics including nocturnal symptoms. Further studies on basophil test-positive and -negative CSU patients can help to better understand CSU endotypes and to develop better management approaches.

Reply to “Is anti-TPO IgG and total IgE clinically useful for the detection of autoimmune chronic spontaneous urticaria”?

“…In addition to aTPO high /IgE low , other markers that are widely available have been linked to aiCSU including basopenia and eosinopenia. 2,4,6,7 We fully agree with the notion that the clinical utility of proposed predictors such as the combined use of aTPO and IgE needs to be further evaluated and that the accuracy of this and other biomarkers for CSU including predictors of aiCSU requires confirmation.…”

“…3 Importantly, aiCSU comes with high disease activity, high rates of autoimmune comorbidities, poor quality of life, and poor response to treatment with antihistamines and omalizumab. [3][4][5] It is, therefore, essential to bring biomarkers and predictors of aiCSU to routine clinical practice. It is also important that these predictors need to be easy to measure and available to all physicians who treat patients with chronic spontaneous urticaria (CSU).…”

“…Furthermore, other factors that may increase the diagnostic accuracy of aTPO high /IgE low , for example, different cut-off values and/ or combination with additional autoimmunity-related markers (eg, basopenia) have to be investigated in further studies (Table I). For example, the component-resolved screening for autoimmune chronic spontaneous urticaria study 4 recently investigated a different cut-off value for total IgE (<30 U/mL). Finally, we measured IgE and aTPO levels only at 1 time point, although they can change over time, and this should also be taken into account in upcoming studies.…”

Urticaria

“…The signs and symptoms of CSU can occur spontaneously at any time of the day but commonly during the evening and night 109 , which may reflect circadian variations in mast cell activation 110 and differences in the underlying pathogenesis. For example, the presence of nocturnal symptoms has been associated with an autoimmune endotype of CSU 111 . Wheals can occur anywhere, but favour the arms and legs 109 .…”

Detection of serum IgG autoantibodies to FcεRIα by ELISA in patients with chronic spontaneous urticaria

“…To evaluate autoimmunity in CSU, basophil autoreactivity functional assay is needed, but it is difficult to apply in every patient in the aspects of technical difficulties, cost, and low availability in the real-world practice [26]. Therefore, basophil histamine release assay and/or basophil activation test were not widely performed in real-world study or practice.…”