Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
RefLab ApS, Copenhagen, Denmark.
J Eur Acad Dermatol Venereol. 2021 Jun;35(6):1338-1345. doi: 10.1111/jdv.17131. Epub 2021 Mar 2.
Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)-activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown.
To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches.
We determined the rates of ASST+/BT- and ASST-/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD).
The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT-: 22%, ASST-/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA-: 18.8% and ASST-/BHRA+: 16.7%) and 31.3% (ASST+/BAT-: 6.3% and ASST-/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA-: 18.8%, ASST-/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD-: 10.0% and ASST-/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002).
The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum-induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.
自身免疫性慢性自发性荨麻疹(CSU)是由肥大细胞(MC)激活自身抗体引起的,可通过自体血清皮肤试验(ASST)和嗜碱性粒细胞试验(BTs)进行筛查。许多 CSU 患者在这些检测中只有一项呈阳性。目前尚不清楚这种情况发生的频率以及原因。
描述 CSU 患者中 ASST 和 BT 检测结果不匹配的发生率,并探讨这些不匹配的可能原因。
我们通过 ASST、两种 BT(嗜碱性粒细胞组胺释放试验,BHRA;嗜碱性粒细胞激活试验,BAT)、MC 组胺释放试验(MCHRA)和体外皮肤微透析(SMD)评估了 48 例 CSU 患者的血清。
已发表的 CSU 研究中 ASST/BT 不匹配率为 31%(ASST+/BT-:22%,ASST-/BT+:9%)。在我们的患者中,ASST/BHRA 和 ASST/BAT 不匹配率分别为 35.4%(ASST+/BHRA-:18.8%和 ASST-/BHRA+:16.7%)和 31.3%(ASST+/BAT-:6.3%和 ASST-/BAT+:25.0%),且两种 BT 之间存在显著相关性(P=0.0002)。使用异源 MC 替代嗜碱性粒细胞进行体外和原位试验也得到了类似的结果(MCHRA 不匹配:47.9%,ASST+/MCHRA-:18.8%,ASST-/MCHRA+:29.2%;SMD 不匹配:40.0%,ASST+/SMD-:10.0%和 ASST-/SMD+:30.0%),且 MCHRA 与 SMD 结果高度相关(P=0.0002)。
ASST 和 BT 在三分之一的 CSU 患者中出现了不一致的结果。这些不匹配不能用嗜碱性粒细胞检测的选择、体外暴露于 CSU 血清的异源细胞类型(嗜碱性粒细胞与肥大细胞)或异源皮肤肥大细胞的实验设置来解释(体外与原位)。因此,CSU 患者的血清诱导性风团似乎涉及调节 MC 脱颗粒的自身皮肤信号。