Morkbak Anne L, Poulsen Steen S, Nexo Ebba
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Clin Chem Lab Med. 2007;45(12):1751-9. doi: 10.1515/CCLM.2007.343.
Evolutionary haptocorrin is the youngest of the cobalamin-binding proteins. It evolved by duplication of the intrinsic factor gene and has been identified in most mammals examined. Its ability to bind both cobalamin and analogues is well established, but apart from that, our knowledge concerning its function and its distribution in adult and foetal life is limited. In this study, we present data on the tissue expression of haptocorrin and on the relation between analogues on haptocorrin and vitamin B(12) status in humans.
Polyclonal antibodies towards haptocorrin were used to study the localisation in foetal and adult tissues by immunohistochemistry. Positive immunoreactions were primarily observed in exocrine glands, the gastrointestinal tract and the respiratory system. ELISA was used for measurement of holo- and total haptocorrin in blood samples from individuals diagnosed with vitamin B(12) deficiency, based on measurement of methylmalonic acid (micromol/L) as evident (>0.75, n=61), suspected (0.29-0.75, n=155) or not present (<0.29, n=170). Cobalamins and holotranscobalamin were measured in the same individuals.
Holohaptocorrin was considerably higher than holohaptocorrin-cobalamins (cobalamins minus holotranscobalamin). The median (25th-75th percentile, pmol/L) for holohaptocorrin analogues (holohaptocorrin minus holohaptocorrin-cobalamins) was higher in deficient [200 (130-240)] compared to the non-deficient [140 (80-200)] individuals (analysis of variance and Tukey's multiple comparison test, p<0.01).
Our results indicate that haptocorrin is widely distributed also in foetal tissues and suggest analogues to accumulate on haptocorrin in vitamin B(12)-deficient individuals, a result that warrants further studies employing methods directly measuring cobalamins and analogues attached to haptocorrin.
进化型钴胺素结合蛋白是钴胺素结合蛋白中最年轻的一种。它通过内因子基因的复制进化而来，已在大多数被检测的哺乳动物中被鉴定出来。其结合钴胺素及其类似物的能力已得到充分证实，但除此之外，我们对其在成年和胎儿期的功能及分布的了解有限。在本研究中，我们展示了关于钴胺素结合蛋白的组织表达以及人类中钴胺素结合蛋白上的类似物与维生素B12状态之间关系的数据。
使用针对钴胺素结合蛋白的多克隆抗体，通过免疫组织化学研究其在胎儿和成人组织中的定位。阳性免疫反应主要在腺体外分泌腺、胃肠道和呼吸系统中观察到。基于甲基丙二酸（微摩尔/升）的测量结果，对于诊断为维生素B12缺乏（明显升高，>0.75，n = 61）、疑似缺乏（0.29 - 0.75，n = 155）或不存在缺乏（<0.29，n = 170）的个体，采用酶联免疫吸附测定法（ELISA）测量血液样本中的全钴胺素结合蛋白和总钴胺素结合蛋白。同时测量这些个体中的钴胺素和全转钴胺素。
全钴胺素结合蛋白显著高于全钴胺素结合蛋白 - 钴胺素（钴胺素减去全转钴胺素）。与非缺乏个体[140（80 - 200）]相比，缺乏个体[200（130 - 240）]中全钴胺素结合蛋白类似物（全钴胺素结合蛋白减去全钴胺素结合蛋白 - 钴胺素）的中位数（第25 - 75百分位数，皮摩尔/升）更高（方差分析和Tukey多重比较检验，p < 0.01）。
我们的结果表明，钴胺素结合蛋白在胎儿组织中也广泛分布，并提示在维生素B12缺乏个体中类似物会在钴胺素结合蛋白上积累，这一结果值得采用直接测量与钴胺素结合蛋白结合的钴胺素及其类似物的方法进行进一步研究。
