Department of Microbiology, Seth G S Medical College and King Edward Memorial Hospital, Mumbai, India.
Department of Cardiology, Seth G S Medical College and King Edward Memorial Hospital, Mumbai, India.
J Med Microbiol. 2021 May;70(5). doi: 10.1099/jmm.0.001355.
Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.
A 组链球菌可引发自身免疫反应，导致急性风湿热（ARF）和风湿性心脏病（RHD）。ARF/RHD 中产生的一些自身抗体针对心肌肌球蛋白 S2 亚片段区域的抗原。然而，人们对这些抗体在疾病过程中的动力学知之甚少。为了确定患者和健康对照者在一段时间内针对宿主组织蛋白 - 心肌肌球蛋白及其 S2 亚片段的肽、原肌球蛋白、层粘连蛋白和角蛋白的抗体反应。我们使用酶联免疫吸附测定（ELISA）来确定以下人群的抗体反应：（1）健康对照者；（2）患有链球菌性咽炎的患者；（3）患有 ARF 伴心炎的患者；（4）接受青霉素预防的 RHD 患者。我们观察到，与健康对照组相比，咽炎组、ARF 组和 RHD 组患者的细胞外蛋白 - 层粘连蛋白和角蛋白的抗体反应明显更高。只有在伴有活动性心炎的 ARF 患者组中，细胞内蛋白 - 心肌肌球蛋白和原肌球蛋白的抗体反应才升高。虽然 ARF 患者对 S2 肽 S2-1-3、8-11、14、16-18、21-22 和 32 的反应性更高，但与健康对照组相比，RHD 组仅对 S2-1、9、11、12 的反应性较高。在 ARF 组中，随着疾病状况稳定，对 S2 肽的反应性降低，而在 RHD 组中，反应性保持不变。相比之下，抗层粘连蛋白和角蛋白的抗体在 RHD 患者中持续存在。我们对宿主蛋白的抗体反应研究结果支持风湿性心炎发生的多步骤假说。血清抗体对 S2 肽的反应动力学差异可能具有作为正在进行的心脏损伤标志物的潜在用途，可用于监测 ARF/RHD 患者。
