Mangla Ankit, Agarwal Nikki, Maruvada Smita
Case Western Reserve University
Maulana Azad Medical College, New Delhi, India
Sickle cell disease (SCD) refers to a group of hemoglobinopathies that include mutations in the gene encoding the beta subunit of hemoglobin. The first description of SCA 'like' disorder was provided by Dr. Africanus Horton in his book The Disease of Tropical Climates and their Treatment (1872). However, it was not until 1910 when Dr. James B Herrick and Dr. Ernest Irons reported noticing 'sickle-shaped' red cells in a dental student (Walter Clement Noel from Grenada). In 1949, independent reports from Dr. James V Neel and Col. E. A. Beet described the patterns of inheritance in patients with SCD. In the same year, Dr. Linus Pauling described the molecular nature of sickle hemoglobin (HbS) in his paper 'Sickle Cell Anemia Hemoglobin.' Ingram Vernon, in 1956, used a fingerprinting technique to describe the replacement of negatively charged glutamine with neutral valine and validated the findings of Linus Pauling. Within the umbrella of SCD, many subgroups exist, namely sickle cell anemia (SCA), hemoglobin SC disease (HbSC), and hemoglobin sickle-beta-thalassemia (beta-thalassemia positive or beta-thalassemia negative). Several other minor variants within the group of SCDs also, albeit not as common as the varieties mentioned above. Lastly, it is essential to mention the sickle cell trait (HbAS), which carries a heterozygous mutation and seldom presents clinical signs or symptoms. Sickle cell anemia is the most common form of SCD, with a lifelong affliction of hemolytic anemia requiring blood transfusions, pain crises, and organ damage. Since the first description of the irregular sickle-shaped red blood cells (RBC) more than 100 years ago, our understanding of the disease has evolved tremendously. Recent advances in the field, more so within the last three decades, have alleviated symptoms for countless patients, especially in high-income countries. In 1984, Platt et al. first reported the use of hydroxyurea in increasing the levels of HbF. Since then, the treatment of sickle cell has taken to new heights by introducing several new agents (voxelotor, crizanlizumab, L-glutamine) and, most recently, gene therapy.
镰状细胞病（SCD）指的是一组血红蛋白病，包括编码血红蛋白β亚基的基因发生突变。非洲裔美国人霍顿博士在其著作《热带气候疾病及其治疗》（1872年）中首次描述了类似镰状细胞贫血（SCA）的病症。然而，直到1910年，詹姆斯·B·赫里克博士和欧内斯特·艾恩斯博士才报告称，他们在一名牙科学生（来自格林纳达的沃尔特·克莱门特·诺埃尔）身上发现了“镰刀状”红细胞。1949年，詹姆斯·V·尼尔博士和E.A.比特上校分别独立报告了SCD患者的遗传模式。同年，莱纳斯·鲍林博士在其论文《镰状细胞贫血血红蛋白》中描述了镰状血红蛋白（HbS）的分子性质。1956年，英格拉姆·弗农使用指纹技术描述了带负电荷的谷氨酰胺被中性缬氨酸取代的情况，证实了莱纳斯·鲍林的研究结果。在SCD范畴内，存在许多亚组，即镰状细胞贫血（SCA）、血红蛋白SC病（HbSC）和血红蛋白镰状-β地中海贫血（β地中海贫血阳性或β地中海贫血阴性）。SCD组内还有其他一些罕见变体，不过不像上述类型那么常见。最后，必须提及镰状细胞性状（HbAS），它携带杂合突变，很少出现临床症状或体征。镰状细胞贫血是SCD最常见的形式，患者终身患有溶血性贫血，需要输血、应对疼痛危机以及预防器官损伤。自从100多年前首次描述不规则的镰刀状红细胞（RBC）以来，我们对这种疾病的认识有了巨大的进展。该领域的最新进展，尤其是在过去三十年里，已经为无数患者缓解了症状，在高收入国家更是如此。1984年，普拉特等人首次报告使用羟基脲来提高胎儿血红蛋白（HbF）水平。从那时起，通过引入几种新药物（如伏洛托珠单抗、crizanlizumab、L-谷氨酰胺），以及最近的基因疗法，镰状细胞病的治疗达到了新高度。
