Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Biochemistry (Mosc). 2013 Jul;78(7):786-97. doi: 10.1134/S0006297913070109.
A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in KD terms) were found to be within the range 10(-4)-10(-6) M. Antibodies to Galβ1-3GlcNAc (Le(C)), 4-HSO3Galβ1-4GalNAc (4'-O-SuLN), Fucα1-3GlcNAc, Fucα1-4GlcNAc, GalNAcα1-3Gal (Adi), Galα1-4Galβ1-4Glc (P(k)), Galα1-4Galβ1-4GlcNAc (P1), GlcNAcα-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of "taboo" is observed for a number of glycans: antibodies to Le(X) and Le(Y), and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on quantitation of anti-glycan nAbs are reported.
存在各种各样的所谓天然抗体（nAbs），即 B-1 细胞产生的免疫球蛋白，它们针对糖。糖的 nAbs 可分为三组：1）保守的 nAbs，即在所有健康供体中，其表位特异性和血液中的水平几乎相同；2）血型抗原的同种抗体；3）与第一组或第二组相关的可塑性抗体，但因在疾病和某些临时情况下（特别是炎症和怀孕）水平变化较大而分开讨论。第三组抗体已被证明是许多疾病的前瞻性标志物，而其异常水平（低于或高于正常值）不一定是疾病/状态的结果。现代微阵列允许确定人类的免疫谱，结果出人意料地广泛。观察到，一些 nAbs 的含量达到总免疫球蛋白的约 0.1%。大多数 nAbs 以 M 类免疫球蛋白为主，占 80-90%。发现它们的亲和力（对单价糖，以 KD 表示）在 10(-4)-10(-6) M 范围内。针对 Galβ1-3GlcNAc（Le(C)）、4-HSO3Galβ1-4GalNAc（4'-O-SuLN）、Fucα1-3GlcNAc、Fucα1-4GlcNAc、GalNAcα1-3Gal（Adi）、Galα1-4Galβ1-4Glc（P(k)）、Galα1-4Galβ1-4GlcNAc（P1）、GlcNAcα-末端聚糖和透明质酸的抗体是在过去十年中发现和研究的 nAbs 之一。与此同时，对于许多聚糖，存在一种“禁忌”：针对 Le(X)和 Le(Y)的抗体，以及健康人几乎没有观察到所有神经节苷脂的抗体。所发现的许多 nAbs 都针对糖的受限内部（核心）部分，该部分直接附着在细胞膜或蛋白质的脂质上。这些 nAbs 的生物学功能尚不清楚；对于抗核心抗体，据推测，其作用是监测异常，特别是癌症抗原的出现。报告了基于定量抗糖 nAbs 的肿瘤诊断的第一个数据。
