<em>Leishmania</em> spp.-Infected Dogs Have Circulating Anti-Skeletal Muscle Autoantibodies Recognizing SERCA1
Francesco Prisco,
Davide De Biase,
Giuseppe Piegari,
Francesco Oriente,
Ilaria Cimmino,
Valeria De Pasquale,
Michele Costanzo,
Pasquale Santoro,
Manuela Gizzarelli,
Serenella Papparella,
Orlando Paciello
Affiliations
Francesco Prisco
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy
Davide De Biase
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy
Giuseppe Piegari
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy
Francesco Oriente
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
Ilaria Cimmino
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
Valeria De Pasquale
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy
Michele Costanzo
Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, 80131 Naples, Italy
Leishmania 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 Ca2+-ATPase 1 (SERCA1). We also found that canine SERCA1 presents several identical traits to the calcium-translocating P-type ATPase of Leishmania infantum. 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.
