The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Caspase 激活和募集结构域 11 ( CARD11 ) 基因编码淋巴细胞抗原受体信号传导所需的支架蛋白。CARD11中的显性失活、功能丧失 (LOF) 致病变异会导致 CARD11 相关特应性，并显性干扰 NF-κB 信号传导 (CADINS) 疾病。CADINS 患者除了反复感染和自身免疫外，还患有严重的特应性表现，包括特应性皮炎、食物过敏和慢性自发性荨麻疹。我们评估了 5 名患有 CADINS 患者的 dupilumab 和 omalizumab 治疗严重特应性症状的反应。使用 T 细胞转染测定验证CARD11突变的致病性，以评估对激活诱导的 NF-κB 信号传导的影响。包括三名患有显性阴性​​ CARD11 LOF 突变的儿童和三名成人。所有人都在婴儿期或幼儿期患上特应性疾病。5 名患者的特应性皮炎很严重，并且对标准的局部和全身药物治疗无效；一名成年人患有慢性自发性荨麻疹。皮下注射 dupilumab 最初用于治疗特应性皮炎，omalizumab 最初用于治疗慢性自发性荨麻疹。所有六名患者的特应性症状均得到快速持续的改善，在随访期间没有出现并发症。以前用于治疗特应性的药物可以减少或停用。总之，使用 dupilumab 和奥马珠单抗治疗 CADINS 患者的严重难治性特应性疾病似乎对患有严重特应性的 CADINS 患者有效且耐受性良好。