Obukhova Polina, Shilova Nadezhda, Pazynina Galina, Tsygankova Svetlana, Popova Inna, Pendu Jacques Le, Bovin Nicolai
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation.
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After V.I. Kulakov of the Ministry of Health Care of the Russian Federation, Moscow, Russian Federation.
Glycoconj J. 2025 Apr 26. doi: 10.1007/s10719-025-10184-z.
Recently, Breiman et al. (2021) reported that the level of anti-Tn in the blood of healthy donors and COVID-19 patients is significantly lower in individuals of blood group A than B. This prompted us to look for qualitative differences in the repertoire of anti-Tn like specificity in individuals of different blood groups (BG). To this end, we isolated antibodies from the pooled sera of BG A and BG B healthy donors using GalNAcα-sepharose, followed by Printed Glycan Array analysis. As expected, antibodies affinity isolated from BG A donors completely lack species directed to canonical (GalNAcα-transferase dependent) A-glycans, such as A (types 1, 2 and 4), GalNAcα1-3(Fucα1-2)Gal, GalNAcα1-3Galβ1-4GlcNAc (linear A), and ALe. Unexpectedly, GalNAcα1-4Galβ1-4GlcNAc, glycan with an unnatural 1-4 bond fell into the same group, i.e., antibodies to it were found only in BG B donors. Other unexpected results include the following: (1) for GalNAcα1-OCHCH(COOH)NH (GalNAcα-OSer, immobilized by NH group) the opposite result was observed, i.e. affinity isolated anti-Tn antibodies of BG A donors demonstrated significantly higher titer than of BG B; (2) in BG A donors, the level of antibodies to GalNGcα1-3GalNAcα (i.e. disaccharide in N-glycolyl form) is close to background, while there is a significant level of these antibodies in the BG B donors. Since antiglycan antibodies are known to play both a protective role in antimicrobial immunity and to promote infectivity, the knowledge gained about the difference in the specificity profiles of anti-Tn antibodies signals the need to take blood group into account in developing therapeutic strategies.
最近，布雷曼等人（2021年）报告称，健康献血者和新冠患者血液中抗Tn水平在A型血个体中显著低于B型血个体。这促使我们寻找不同血型（BG）个体中抗Tn样特异性库的质量差异。为此，我们使用N-乙酰半乳糖胺α-琼脂糖从A型血和B型血健康献血者的混合血清中分离抗体，随后进行印刷聚糖阵列分析。正如预期的那样，从A型血献血者中分离出的抗体亲和力完全缺乏针对典型（依赖N-乙酰半乳糖胺α-转移酶）A聚糖的种类，如A（1、2和4型）、N-乙酰半乳糖胺α1-3（岩藻糖α1-2）半乳糖、N-乙酰半乳糖胺α1-3半乳糖β1-4N-乙酰葡糖胺（线性A）和ALe。出乎意料的是，具有非天然1-4键的聚糖N-乙酰半乳糖胺α1-4半乳糖β1-4N-乙酰葡糖胺属于同一组，即仅在B型血献血者中发现了针对它的抗体。其他意外结果包括：（1）对于N-乙酰半乳糖胺α1-OCHCH（COOH）NH（N-乙酰半乳糖胺α-丝氨酸，通过NH基团固定），观察到相反的结果，即从A型血献血者中分离出的具有亲和力的抗Tn抗体滴度显著高于B型血；（2）在A型血献血者中，针对N-糖基化形式的N-乙酰神经氨酸α1-3N-乙酰半乳糖胺α（即二糖）的抗体水平接近背景值，而在B型血献血者中这些抗体水平显著。由于已知抗聚糖抗体在抗菌免疫中既起保护作用又促进感染性，所获得的关于抗Tn抗体特异性谱差异的知识表明在制定治疗策略时需要考虑血型。
