Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study

Abstract

Background: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU.Methods: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). Results:Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively.Conclusions: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management. K E Y W O R D Sautoimmune CSU, autologous serum skin test, basophil activation assays, chronic spontaneous urticaria, IgG autoantibodies

Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020

“…Most CSU patients treated with omalizumab become symptom-free within the first month of their first injection. This is in line with type I autoimmunity, where anti-IgE rapidly binds free IgE, including IgE against autoantigens, and IgE/anti-IgE complexes bind autoallergens, thereby reducing MC degranu- [112][113][114] Diagnosis total auto-IgE and specific IgE to autoallergens 1 in type I [115], triple positivity: BHRA/BAT+ASST+WB/ELISA+ in type IIb [24,25] Disease activity/severity tends to be higher in type IIb [12, 14, 25, 111] 2 Disease duration tends to be longer in type IIb as shown in some [116,117] but not all [25] studies…”

“…Rates of concomitant autoimmune diseases tend to be higher in type IIb [25,[118][119][120][121] Rates of concomitant allergic diseases might be higher in type I [119] Total IgE levels low in type IIb and normal or high in type I [14,25] Basopenia rates might be higher in type IIb [24, 111] 2 Eosinopenia rates tend to be higher in type IIb [122] C-reactive protein levels may be higher in type IIb [25,123] ANA positivity rates may be higher in type IIb [124] Responder rates to sgAHs may be lower in type IIb [122][123][124][125] Responder rates to omalizumab high in type I [28] and low in type IIb [62,122,126] Speed of response to omalizumab slow in type IIb [127] Immunosuppressive therapy can be effective in type IIb [128-134] 3 TPO, thyroperoxidase; TG, thyroglobulin; TF, tissue factor; IL, interleukin; dsDNA, double-stranded DNA; BHRA, basophil histamine release assay; BAT, basophil activation test; ASST, autologous serum skin test; WB, Western blot; ELISA, enzyme-linked immunosorbent assay; CRP, C-reactive protein; ANA, antinuclear antibodies; sgAHs, second-generation antihistamines. 1 Measured by ELISA or radioimmunoassay.…”

“…In the recent PURIST study, the first to characterize CSU patients who are positive for all three defining markers of type IIb autoimmune CSU, i.e., IgG-anti-FcεRI/ IgE-positive, basophil test-positive, and ASST-positive, 8% of 184 patients were triple-positive, i.e., had bona fide type IIb CSU [25]. These patients showed higher IgGanti-TPO levels and higher rates of elevated IgG-anti-TPO as well as lower IgE levels and higher rates of low IgE as compared to triple-negative patients.…”

Targeted Therapy for Chronıc Spontaneous Urtıcarıa: Ratıonale and Recent Progress

“…These findings show that the patients exhibiting the features of autoimmune CSU with type IIb autoimmunity (positive in vivo reactivity (ASST), positive in vitro basophil reactivity (BHRA) and presence of IgG autoantibodies against FcεRI) are less likely to completely respond to omalizumab [53,54]. However, considering that only 8% of the patients in the PURIST study fulfilled all three criteria, novel clinical or laboratory biomarkers of response to omalizumab are still needed [53]. The clinical and laboratory predictors of response to omalizumab in patients with CSU are given in Table 3.…”

“…Studies investigating the factors associated with response to omalizumab have revealed that patients with a positive basophil histamine release assay (BHRA), a positive autologous serum skin test (ASST), lower baseline basophil FcεRI expression, lower IgE levels, and a lower ratio of 4-week/baseline IgE are more likely to show no response or a slow response [46][47][48][49][50][51][52]. These findings show that the patients exhibiting the features of autoimmune CSU with type IIb autoimmunity (positive in vivo reactivity (ASST), positive in vitro basophil reactivity (BHRA) and presence of IgG autoantibodies against FcεRI) are less likely to completely respond to omalizumab [53,54]. However, considering that only 8% of the patients in the PURIST study fulfilled all three criteria, novel clinical or laboratory biomarkers of response to omalizumab are still needed [53].…”