Kelly-Worden Marie, Hammer Leslie, Gebhard Robyn, Schrader Lauran, Griffin Marley, Cooper Dalahnna
Department of Physiology and Health Science, Ball State University, Muncie, IN 47306, USA.
J Pharm Bioallied Sci. 2014 Jul;6(3):198-204. doi: 10.4103/0975-7406.135247.
Systemic lupus erythematosus (SLE) is characterized by the presence of anti-nuclear antibodies (ANAs) in the serum of patients. These antibodies may cross over into the brain resulting in the development of neuropsychiatric symptoms and result in abnormal pathology in other organs such as the heart and kidneys.
The objective of this study was to determine if SLE pathology could be detected in the hearts and brains of rats injected with positive human ANA serum.
Lewis rats (n = 31) were selected for this study due to documented research already performed with this strain in the investigation of serum sickness, encephalitis and autoimmune related carditis. Rats were injected once a week with either ANA positive or negative control serum or saline. Hearts were examined for initial signs of heart disease including the presence of lipid deposits, vegetation, increased ventricular thickness and a change in heart weight. Brains were examined for the presence of human antibody and necrotic lesions. Animals were observed for outward signs of neuropathy as well. Blood samples were taken in order to determine final circulating concentrations of IgG and monitor histamine levels.
Animals injected with ANA were significantly higher for lipid deposits in the heart and an increased ventricular thickness was noted. One animal even displayed Libman-Sacks endocarditis. Brains were positive for the presence of human IgG and diffuse internal lesions occurred in 80% of the ANA positive serum injected animals examined. Blood histamine levels were not significantly different, but actually lower than controls by the end of the experiment.
Since human antibodies were detected in the brain, further studies will have to identify which antibody cross reactions are occurring within the brain, examine cell infiltration as well as characterize the antibodies associated with more destructive consequences such as lesion formation.
系统性红斑狼疮(SLE)的特征是患者血清中存在抗核抗体(ANA)。这些抗体可能会进入大脑,导致神经精神症状的出现,并在心脏和肾脏等其他器官中引发异常病理变化。
本研究的目的是确定在注射了阳性人ANA血清的大鼠的心脏和大脑中是否能检测到SLE病理变化。
由于此前已对该品系大鼠进行过血清病、脑炎和自身免疫性相关心肌炎的研究,因此本研究选用了31只Lewis大鼠。大鼠每周注射一次ANA阳性或阴性对照血清或生理盐水。检查心脏是否有心脏病的初始迹象,包括脂质沉积、赘生物、心室厚度增加和心脏重量变化。检查大脑中是否存在人抗体和坏死性病变。还观察动物是否有神经病变的外在迹象。采集血样以确定IgG的最终循环浓度并监测组胺水平。
注射ANA的动物心脏中的脂质沉积明显更多,且心室厚度增加。有一只动物甚至出现了Libman-Sacks心内膜炎。大脑中检测到人IgG呈阳性,在检查的80%注射ANA阳性血清的动物中出现了弥漫性内部病变。血组胺水平无显著差异,但在实验结束时实际上低于对照组。
由于在大脑中检测到了人抗体,进一步的研究将必须确定大脑中发生了哪些抗体交叉反应,检查细胞浸润情况,并对与更具破坏性后果(如病变形成)相关的抗体进行表征。