Prisco Francesco, De Biase Davide, Piegari Giuseppe, Oriente Francesco, Cimmino Ilaria, De Pasquale Valeria, Costanzo Michele, Santoro Pasquale, Gizzarelli Manuela, Papparella Serenella, Paciello Orlando
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy.
Research Unit (URT) Genomic of Diabetes, Department of Translational Medicine, Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), University of Naples Federico II, 80131 Naples, Italy.
Pathogens. 2021 Apr 12;10(4):463. doi: 10.3390/pathogens10040463.
spp. infection is associated with an inflammatory myopathy (IM) in dogs. The pathomechanism underlying this disorder is still elusive, however, the pattern of cellular infiltration and MHC I and II upregulation indicate an immune-mediated myositis. This study aimed to investigate the presence of autoantibodies targeting the skeletal muscle in sera of leishmania-infected dogs and individuate the major autoantigen. We tested sera from 35 leishmania-infected dogs and sera from 10 negative controls for the presence of circulating autoantibodies with indirect immunofluorescence. Immunoblot and mass spectrometry were used to identify the main target autoantigen. Immunocolocalization and immunoblot on immunoprecipitated muscle proteins were performed to confirm the individuated major autoantigen. We identified circulating autoantibodies that recognize skeletal muscle antigen(s) in sera of leishmania-infected dogs. The major antigen was identified as the sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1). We also found that canine SERCA1 presents several identical traits to the calcium-translocating P-type ATPase of . In the present study, we defined circulating anti-SERCA1 autoantibodies as part of the pathogenesis of the leishmania-associated IM in dogs. Based on our data, we hypothesize that antigen mimicry is the mechanism underlying the production of these autoantibodies in leishmania-infected dogs.
利什曼原虫感染与犬类的炎性肌病(IM)有关。然而,这种疾病的发病机制仍然难以捉摸,不过细胞浸润模式以及MHC I和II上调表明这是一种免疫介导的肌炎。本研究旨在调查利什曼原虫感染犬血清中靶向骨骼肌的自身抗体的存在情况,并确定主要自身抗原。我们用间接免疫荧光法检测了35只利什曼原虫感染犬的血清和10只阴性对照犬的血清中循环自身抗体的存在情况。免疫印迹和质谱法用于鉴定主要的靶自身抗原。对免疫沉淀的肌肉蛋白进行免疫共定位和免疫印迹,以确认所确定的主要自身抗原。我们在利什曼原虫感染犬的血清中鉴定出了识别骨骼肌抗原的循环自身抗体。主要抗原被鉴定为肌浆网/内质网钙ATP酶1(SERCA1)。我们还发现犬SERCA1与[未提及的物种]的钙转运P型ATP酶有几个相同的特征。在本研究中,我们将循环抗SERCA1自身抗体定义为犬类利什曼原虫相关IM发病机制的一部分。基于我们的数据,我们假设抗原模拟是利什曼原虫感染犬产生这些自身抗体的潜在机制。