Revivicor Incorporated, United Therapeutics, Blacksburg, Va.
Duke Congenital Heart Surgery Research and Training Laboratory, Durham, NC.
J Thorac Cardiovasc Surg. 2022 Dec;164(6):e411-e424. doi: 10.1016/j.jtcvs.2021.03.100. Epub 2021 Apr 9.
Galactose-α-1,3-galactose (alpha-gal) is a carbohydrate that is ubiquitously expressed in all mammals except for primates and humans. Patients can become sensitized to this antigen and develop alpha-gal syndrome (AGS), or a red meat allergy. Symptoms range from generalized gastroenteritis and malaise to anaphylaxis, and in endemic areas, the prevalence can be as high as 20%. Although AGS patients commonly avoid alpha-gal by avoiding meat, patients have also developed symptoms due to animal-derived medical products and devices. With the rise in transcatheter aortic valve replacement, we investigate the immunogenicity of common cardiac materials and valves.
To assess the in vitro immunoglobulin E response toward common medical products, including cardiac patch materials and bioprosthetic valves in patients with AGS.
Immunoblot and immunohistochemistry techniques were applied to assess immunoglobulin E reactivity to various mammalian derived tissues and medical products for patients with AGS.
AGS serum showed strong reactivity to all of the commercially available, nonhuman products tested, including various decellularized cardiac patch materials and bioprosthetic aortic valves. AGS serum did not react to tissues prepared using alpha-gal knockout pigs.
Despite commercial decellularization processes, alpha-gal continues to be present in animal-derived medical products, including bioprosthetic valves. Serum from patients with AGS demonstrates a strong affinity for these products in vitro. This may have serious potential implications for sensitized patients undergoing cardiac surgery, including early valve failure and accelerated coronary artery disease.
半乳糖-α-1,3-半乳糖(alpha-gal)是一种碳水化合物,除了灵长类动物和人类之外,所有哺乳动物都普遍表达。患者可能会对这种抗原产生敏感性,从而患上 alpha-gal 综合征(AGS)或红肉过敏。症状范围从全身肠胃炎和不适到过敏反应,在流行地区,患病率可能高达 20%。尽管 AGS 患者通常通过避免肉类来避免 alpha-gal,但患者也因动物源性医疗产品和设备而出现症状。随着经导管主动脉瓣置换术的兴起,我们研究了常见心脏材料和瓣膜的免疫原性。
评估 AGS 患者常见医疗产品(包括心脏补片材料和生物假体瓣膜)的体外免疫球蛋白 E 反应。
应用免疫印迹和免疫组织化学技术评估 AGS 患者对各种哺乳动物来源的组织和医疗产品的免疫球蛋白 E 反应性。
AGS 血清对所有测试的市售非人类产品均表现出强烈的反应性,包括各种去细胞化心脏补片材料和生物假体主动脉瓣。AGS 血清未与使用 alpha-gal 敲除猪制备的组织发生反应。
尽管经过商业去细胞化处理,但 alpha-gal 仍然存在于动物源性医疗产品中,包括生物假体瓣膜。AGS 患者的血清在体外对这些产品表现出强烈的亲和力。这可能对接受心脏手术的致敏患者产生严重的潜在影响,包括早期瓣膜失效和加速冠状动脉疾病。