UTILIDAD DE LAS PROTEÍNAS DE FASE AGUDA EN EL LÍQUIDO CEFALORRAQUÍDEO CANINO PARA EL DIAGNÓSTICO DE LA MENINGOENCEFALOMIELITIS DE ORIGEN DESCONOCIDO

Autores/as

  • Maria Elena Verdú Serrano Departamento de Sanidad Animal, Facultad de Veterinaria
  • Alberto Muñoz Prieto Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria
  • Isidro Mateo Pampliega Hospital Clínico Veterinario Vetsia, Leganés, Madrid
  • Juan Diego Garcia Martínez Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria
DOI: https://doi.org/10.6018/analesvet.562071
Palabras clave: proteína C reactiva, haptoglobina, perro, respuesta de fase aguda, sistema nervioso central, meninges, encéfalo, biofluidos, biomarcadores

Resumen

El sistema inmunitario facilita la defensa de los seres vivos, que se desencadena a través de la respuesta de fase aguda, generándose las proteínas de fase aguda. Estas proteínas, medidas en suero, resultan de utilidad. El uso de biomarcadores para el diagnóstico precoz de enfermedades inflamatorias del sistema nervioso central (SNC), está en auge en medicina humana. En el caso de las meningoencefalomielitis de origen desconocido (MOD), no hay estudios con una información relevante que sea capaz de solventar el gran inconveniente de no poder obtener un diagnóstico definitivo, que no sea de manera postmortem. La medición de proteínas de fase aguda, como la proteína C reactiva (CRP) y la haptoglobina en el líquido cefalorraquídeo (LCR) podría ayudar a solventar este problema. El objetivo de esta investigación es valorar si estas proteínas se pueden detectar en el LCR, mediante un analizador bioquímico automatizado y estudiar la existencia de alteraciones en animales con MOD. Para ello, los animales incluidos en el estudio se dividieron en un grupo control, compuesto por perros sin MOD y un grupo problema, subdividido en perros con MOD y perros con MOD tratados con corticoides. Para la medición de estos parámetros se utilizó el analizador Olympus AU600®. Para realizar el estudio comparativo entre grupos se aplicó la prueba no paramétrica de Kruskal-Wallis, seguido del test de Dunn para comparaciones múltiples. La CRP no mostró variaciones estadísticamente significativas, mientras que la haptoglobina no se pudo detectar en el LCR, por lo que se debería valorar su medición con técnicas más sensibles que permitan su cuantificación.

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Adamo, P. F., Adams, W. M., & Steinberg, H. (2007). Granulomatous meningoencephalomyelitis in dogs. Compendium (Yardley, PA), 29(11), 678–690.

Andersen, C. B. F., Stødkilde, K., Sæderup, K. L., Kuhlee, A., Raunser, S., Graversen, J. H., & Moestrup, S. K. (2017). Haptoglobin. Antioxidants and Redox Signaling, 26(14), 814–831. https://doi.org/10.1089/ars.2016.6793

Andersen-Ranberg, E., Berendt, M., & Gredal, H. (2021). Biomarkers of non-infectious inflammatory CNS diseases in dogs — Where are we now? Part I: Meningoencephalitis of unknown origin. Veterinary Journal, 273, 105678. https://doi.org/10.1016/j.tvjl.2021.105678

Anderson, K. M., Welsh, C. J., Young, C., Levine, G. J., Kerwin, S. C., Boudreau, C. E., Reyes, I., Mondragon, A., Griffin, J. F., Cohen, N. D., & Levine, J. M. (2015). Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury. Journal of Neurotrauma, 32(21), 1658–1665. https://doi.org/10.1089/neu.2015.3895

Bielekova, B., & Pranzatelli, M. R. (2017). Promise, Progress, and Pitfalls in the Search for Central Nervous System Biomarkers in Neuroimmunological Diseases: A Role for Cerebrospinal Fluid Immunophenotyping. Seminars in Pediatric Neurology, 24(3), 229–239. https://doi.org/10.1016/j.spen.2017.08.001

Black, S., Kushner, I., & Samols, D. (2004). C-reactive protein. Journal of Biological Chemistry, 279(47), 48487–48490. https://doi.org/10.1074/jbc.R400025200

Blennow, K., & Zetterberg, H. (2018). Biomarkers for Alzheimer’s disease: current status and prospects for the future. Journal of Internal Medicine, 284(6), 643–663. https://doi.org/10.1111/joim.12816

Briles, D. E., Forman, C., Horowitz, J. C., Volanakis, J. E., Benjamin, W. H., McDaniel, L. S., Eldridge, J., & Brooks, J. (1989). Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens. Infection and Immunity, 57(5), 1457–1464. https://doi.org/10.1128/iai.57.5.1457-1464.1989

Buser, F. C., Schweighauser, A., im Hof-Gut, M., Bigler, B., Marti, E., Mirkovitch, J., & Francey, T. (2019). Evaluation of C-reactive protein and its kinetics as a prognostic indicator in canine leptospirosis. Journal of Small Animal Practice, 60(8), 477–485. https://doi.org/10.1111/jsap.13004

Caspi, D.; Snel, F. W. J. J.; Batt Bennet, D.; Rutteman, G. R.; Hartman, E. G.; Baltz, M. L.; Gruys, E.; Pepys, B. M. (1987). C reactive protein in dogs. American Journal of Veterinary Research, 48, 919–921.

Cerón, J. J., Eckersall, P. D., & Martínez-Subiela, S. (2005). Acute phase proteins in dogs and cats: Current knowledge and future perspectives. Veterinary Clinical Pathology, 34(2), 85–99. https://doi.org/10.1111/j.1939-165X.2005.tb00019.x

Chamoun, V., Zeman, A., Blennow, K., Fredman, P., Wallin, A., Keir, G., Giovannoni, G., & Thompson, E. J. (2001). Haptoglobins as markers of blood-CSF barrier dysfunction: The findings in normal CSF. Journal of the Neurological Sciences, 182(2), 117–121. https://doi.org/10.1016/S0022-510X(00)00461-5

Cloquell M., Ana; Pampliega, Isidro M. (2010). Meningoencefalitis de origen desconocido en el perro. Revista Médica de Chile, 129, 647–652. https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0718-221X2015000300013

Cornelis, I., van Ham, L., Gielen, I., de Decker, S., & Bhatti, S. F. M. (2019). Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: A review. Veterinary Journal, 244, 37–44. https://doi.org/10.1016/j.tvjl.2018.12.007

Cynthia, M.; Kahn, B. A. (2007). Manual Merck de Veterinaria (E. Océano, Ed.; 6o Edición).

Dati, F., Schumann, G., Thomas, L., Aguzzi, F., Baudner, S., Bienvenu, J., Blaabjerg, O., Blirup-Jensen, S., Carlström, A., Petersen, P. H., Johnson, A. M., Milford-Ward, A., Ritchie, R. F., Svendsen, P. J., & Whicher, J. (1996). Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Cl. European Journal of Clinical Chemistry and Clinical Biochemistry : Journal of the Forum of European Clinical Chemistry Societies, 34(6), 517–520.

de Risio, L., Bhatti, S., Muñana, K., Penderis, J., Stein, V., Tipold, A., Berendt, M., Farqhuar, R., Fischer, A., Long, S., Mandigers, P. J. J., Matiasek, K., Packer, R. M. A., Pakozdy, A., Patterson, N., Platt, S., Podell, M., Potschka, H., Batlle, M. P., … Volk, H. A. (2015). International veterinary epilepsy task force consensus proposal: Diagnostic approach to epilepsy in dogs. BMC Veterinary Research, 11(1). https://doi.org/10.1186/s12917-015-0462-1

di Masi, A., de Simone, G., Ciaccio, C., D’Orso, S., Coletta, M., & Ascenzi, P. (2020). Haptoglobin: From hemoglobin scavenging to human health. Molecular Aspects of Medicine, 73(March), 100851. https://doi.org/10.1016/j.mam.2020.100851

Eaton, J. W., Brandt, P., Mahoney, J. R., & Lee, J. T. (1982). Haptoglobin: A natural bacteriostat. Science, 215(4533), 691–693. https://doi.org/10.1126/science.7036344

Eckersall, P. D., & Bell, R. (2010). Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. Veterinary Journal, 185(1), 23–27. https://doi.org/10.1016/j.tvjl.2010.04.009

Falcón-Cordón, Y., Tvarijonaviciute, A., Montoya-Alonso, J. A., Muñoz-Prieto, A., Caro-Vadillo, A., & Carretón, E. (2022). Evaluation of acute phase proteins, adiponectin and endothelin-1 to determine vascular damage in dogs with heartworm disease (Dirofilaria immitis), before and after adulticide treatment. Veterinary Parasitology, 309, 109759. https://doi.org/10.1016/j.vetpar.2022.109759

Fergestad, M. E.; Johr, T. H.; Krontreit, R. I.; Skancke, E. (2016). Serum concentration of gastrin, cortisol and C-reactive protein in a group of Norwegian sled dogs during training and after endurance racing: a prospective cohort study. Acta Veterinaria Scandinavica, 58(24).

Gaetani, L., Blennow, K., Calabresi, P., di Filippo, M., Parnetti, L., & Zetterberg, H. (2019). Neurofilament light chain as a biomarker in neurological disorders. Journal of Neurology, Neurosurgery and Psychiatry, 1–12. https://doi.org/10.1136/jnnp-2018-320106

Gebhart, C.; Hirschberger, J.; Rau, S.; Arndt, G.; Kramer, K.; Schweigert, F. J.; Brunnberg, L.; Kaspers, B.; Kohn, B. (2009). Use of C-reactive protein to predict outcome in dogs with systemic inflammatory response syndrome or sepsis. Journal of Veterinary Emergency and Critical Care, 19(5), 450–458.

Granger, N., Smith, P. M., & Jeffery, N. D. (2010). Clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: A systematic review of 457 published cases from 1962 to 2008. Veterinary Journal, 184(3), 290–297. https://doi.org/10.1016/j.tvjl.2009.03.031

Heinrich, P. C.; Castell, J. V.; Aandus, T. (1990). Interleukin-6 and the acute phase response. Biochemical Journal, 265, 621–636.

Jain, N. C. (1989). Acute phase proteins. En: Current veterinary Therapy X: Small animal practice. W B Saunders, Philadelphia., 468–471.

Karlsson, I., Hagman, R., Johannisson, A., Wang, L., Södersten, F., & Wernersson, S. (2015). Multiplex cytokine analyses in dogs with pyometra suggest involvement of KC-like chemokine in canine bacterial sepsis. Veterinary Immunology and Immunopathology, 170, 41–46. https://doi.org/10.1016/j.vetimm.2016.01.005

Kasvosve, I., Speeckaert, M. M., Speeckaert, R., Masukume, G., & Delanghe, J. R. (2010). Haptoglobin Polymorphism and Infection. Advances in Clinical Chemistry, 50(10), 23–46. https://doi.org/10.1016/S0065-2423(10)50002-7

Kim, J., Otto, N., Conti, C. J., Gimenz-Conti, I. B., & Walker, C. L. (2012). ELISA. Methods and Protocols. Springer Protocols. In Methods in Molecular Biology (Vol. 821). https://doi.org/10.1007/978-1-61779-430-8_12

Kocaturk, M.; Tvarijonariciute, A.; Martinez-Subiela, S.; Tecles, F.; Eralp, O.; Yilmaz, Z.; Ceron, J. J. (2015). Inflammatory and aoxidative biomarkers of disease severity in dogs with parvoviral enteritis. Journal of Small Animal Practice, 56(2), 119–124.

Kushner, I.; Gewurz, H.; Benson, M. D. (1981). C-reactive protein and the acute phase response. Journal of Laboratory Clinical Medicine, 97, 739–749.

Kushner, I.; Mackiewicz, A. (1993). Acute Phase Response: an overview En: Acute Phase Protein. Molecular biology, biochemistry and clinical applications pp. CRC Press London, 3(19).

Kwon, E. H., Tennagels, S., Gold, R., Gerwert, K., Beyer, L., & Tönges, L. (2022). Update on CSF Biomarkers in Parkinson’s Disease. Biomolecules, 12(2), 1–15. https://doi.org/10.3390/biom12020329

Lezmi, S., Toussaint, Y., Prata, D., Lejeune, T., Ferreira-Neves, P., Rakotovao, F., Fontaine, J. J., Marchal, T., & Cordonnier, N. (2007). Severe necrotizing encephalitis in a Yorkshire terrier: Topographic and immunohistochemical study. Journal of Veterinary Medicine Series A: Physiology Pathology Clinical Medicine, 54(4), 186–190. https://doi.org/10.1111/j.1439-0442.2007.00925.x

Lowrie, M., Smith, P. M., & Garosi, L. (2013). Meningoencephalitis of unknown origin: investigation of prognostic factors and outcome using a standard treatment protocol. Veterinary Record, 172(20), 527. https://doi.org/10.1136/vr.101431

Makimura, S. y Suzuki, N. (1982). Quantitative determination of bovine serum haptoglobin and its elevation in some inflammatory diseases. Japanese Journal Veterinary Science, 44, 15–21.

Malin, K., & Witkowska-Piłaszewicz, O. (2022). C-Reactive Protein as a Diagnostic Marker in Dogs: A Review Animals, 12(20). https://doi.org/10.3390/ani12202888

Martínez-Subiela, S., Caldin, M., Parra, M. D., Ottolini, N., Bertolini, G., Bernal, L. J., García-Martinez, J. D., & Cerón, J. J. (2011). Canine C-reactive protein measurements in cerebrospinal fluid by a time-resolved immunofluorimetric assay. Journal of Veterinary Diagnostic Investigation, 23(1), 63–67. https://doi.org/10.1177/104063871102300109

Martínez-Subiela, S., Tecles, F., Parra, M. D., & Cerón, J. J. (2001). Proteínas De Fase Aguda: Conceptos Básicos Y Principales Aplicaciones Clínicas En Medicina Veterinaria. Anales de Veterinaria de Murcia, 97(17), 114.

Martin-Vaquero, P.; C. da Costa, R.; j. Allen, M.; A. Moore, S.; K. Keirsey, J. and B. Green, K. (2016). Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy. Spine, 40(9), 601–612. https://doi.org/10.1097/BRS.0000000000000831.Proteomic

Melgar, S., Karlsson, A., & Michaëlsson, E. (2005). Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: Correlation between symptoms and inflammation. American Journal of Physiology - Gastrointestinal and Liver Physiology, 288(6 51-6), 1328–1338. https://doi.org/10.1152/ajpgi.00467.2004

Méndez, J. C., Carretón, E., Martínez-Subiela, S., Tvarijonaviciute, A., Cerón, J. J., & Montoya-Alonso, J. A. (2015). Acute phase protein response in heartworm-infected dogs after adulticide treatment. Veterinary Parasitology, 209(3–4), 197–201. https://doi.org/10.1016/j.vetpar.2015.02.036

Meyer, D. J.; Harvey, J. W. (2007). Medicina Laboratorial Veterinaria, Interpretación y diagnosis (Elsevier, Ed.; 3o Edición).

Morales, C., & Montoliu, P. (2012). Neurología Canina y Felina (M. E. Veterinarias, Ed.; 1o Edición).

Nakamura, M., Takahashi, M., Ohno, K., Koshino, A., Nakashima, K., Setoguchi, A., Fujino, Y., & Tsujimoto, H. (2008). C-reactive protein concentration in dogs with various diseases. Journal of Veterinary Medical Science, 70(2), 127–131. https://doi.org/10.1292/jvms.70.127

Nessler, J. N., Jo, W. K., Osterhaus, A. D. M. E., Ludlow, M., & Tipold, A. (2021). Canine Meningoencephalitis of Unknown Origin—The Search for Infectious Agents in the Cerebrospinal Fluid via Deep Sequencing. Frontiers in Veterinary Science, 8(December), 1–6. https://doi.org/10.3389/fvets.2021.645517

Oh, S. K., Pavlotsky, N., & Tauber, A. I. (1990). Specific binding of haptoglobin to human neutrophils and its functional consequences. Journal of Leukocyte Biology, 47(2), 142–148. https://doi.org/10.1002/jlb.47.2.142

Oliphant, B. J., Barnes Heller, H. L., & White, J. M. (2017). Retrospective Study Evaluating Associations Between Midline Brain Shift on Magnetic Resonance Imaging and Survival in Dogs Diagnosed With Meningoencephalitis of Unknown Etiology. Veterinary Radiology and Ultrasound, 58(1), 38–43. https://doi.org/10.1111/vru.12434

Olsson, B., Lautner, R., Andreasson, U., Öhrfelt, A., Portelius, E., Bjerke, M., Hölttä, M., Rosén, C., Olsson, C., Strobel, G., Wu, E., Dakin, K., Petzold, M., Blennow, K., & Zetterberg, H. (2016). CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. The Lancet Neurology, 15(7), 673–684. https://doi.org/10.1016/S1474-4422(16)00070-3

Pannen, B. H. J.; Robotham, J. L. (1995). The acute-phase response. New Horizons, 3, 183–197.

Pardo-Marin, L., Ceron, J. J., Tecles, F., Baneth, G., & Martínez-Subiela, S. (2020). Comparison of acute phase proteins in different clinical classification systems for canine leishmaniosis. Veterinary Immunology and Immunopathology, 219. https://doi.org/10.1016/j.vetimm.2019.109958

Pellegrino, F.; Suraniti, A.; Garibaldi, L. (2003). El libro de la Neurología para la Práctica clínica (E. Intermédica, Ed.; 1o Edición).

Polizopoulou, Z. S.; Koutinas, C. K.; Ceron, J. J.; Tvarijonariciute, A.; Martinez-Subiela, S.; Dasopoulou, A.; York, M. J.; Roman, I. F.; Gandhi, M.; Patel, S.; O`Brien, P. j. (2015). Correlation of serum cardiac troponim I and acute phase protein concentrations with clinical staging in dogs with gegenerative mitral valve disease. Veterinary Clinical Pathology, 44(3), 397–404.

Portero F., M. (2018). Biomarcadores en líquido cefalorraquideo en perros con meningoencefalitis de origen desconocido. Valor pronóstico. 295. https://eprints.ucm.es/49911/1/T40547.pdf

R. Platt, Simon y J. Olby, Natasha. (2008). Manual de Neurología en pequeños animales (E. S, Ed.; 2o Edición).

Reimann, M J, Ljunguall, I.; Hillstrom, A; Moller, J. E.; Hogman, R.; Falk, T.; Hogland, K.; Haggstrom, J.; Olsen, L. H. (2016). Increases serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease. Veterinary Journal, 209, 113–118.

Rikihisa, Y.; Yamamoto, S.; Kwak, I.; Iqbal, Z.; Kociba, G.; Mott, J.; Chichanasiriwithaya, W. (1994). C-reactive protein and a1-acid glycoprotein levels in dogs infected with Ehrlichia canis. Journal of Clinical Microbiology, 32, 912–917.

Satoh, H., Yamato, O., Asano, T., Yonemura, M., Yamauchi, T., Hasegawa, D., Orima, H., Arai, T., Yamasaki, M., & Maede, Y. (2007). Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: Possible use for assessment of a therapeutic regimen. Brain Research, 1133(1), 200–208. https://doi.org/10.1016/j.brainres.2006.11.039

Schatzberg, S. J. (2010). Idiopathic Granulomatous and Necrotizing Inflammatory Disorders of the Canine Central Nervous System. Veterinary Clinics of North America - Small Animal Practice, 40(1), 101–120. https://doi.org/10.1016/j.cvsm.2009.09.003

Selting, K. A.; Sharp, C. R.; Ringold, R.; Knouse, J. (2015). Serum thymidine kinase 1 and C-reactive protein as biomarkers for screening clinically healthy dogs for occult disease. Veterinary and Comparative Oncology, 13(4), 373–384.

Shafie, I. N. F., McLaughlin, M., Burchmore, R., Lim, M. A. A., Montague, P., Johnston, P. E. J., Penderis, J., & Anderson, T. J. (2014). The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog. Cell Stress and Chaperones, 19(3), 311–320. https://doi.org/10.1007/s12192-013-0457-4

Shih, A. W. Y., Mcfarlane, A., & Verhovsek, M. (2014). Haptoglobin testing in hemolysis: Measurement and interpretation. American Journal of Hematology, 89(4), 443–447. https://doi.org/10.1002/ajh.23623

Solter, P.; Hoffmann, W. E.; Hungerford; L. L.; Siegel, J. P. ; S., & Denis, S. H.; Dorner, J. L. (1991). Haptoglobin and Ceruloplasmin as determinants of inflammation in dogs. American Journal of Veterinary Research, 52, 1738–1742.

Szalai, A. J., van Ginkel, F. W., Wang, Y., McGhee, J. R., & Volanakis, J. E. (2000). Complement-Dependent Acute-Phase Expression of C-Reactive Protein and Serum Amyloid P-Component. The Journal of Immunology, 165(2), 1030–1035. https://doi.org/10.4049/jimmunol.165.2.1030

Waritani, T., Cutler, D., & Chang, J. (2020). Development of canine C-reactive protein assays. Acta Veterinaria Scandinavica, 62(1), 10–14. https://doi.org/10.1186/s13028-020-00549-9

Whicher J. T. y Westacott, C. I. (1992). The acute phase response. En: Biochemistry of Inflammation. Kluwer Academic Londres., 243–271.

Yamamoto, S.; Shida, T.; Honda, M.; Ashida, Y.; Rikihisa, Y.; Odakura, M.; Hayashi, S.; Nomura, M.; Isayama, Y. (1994). Serum C-reactive protein and immuneresponses in dogs inoculated with bordetellabronchiseptica (phase-i cells). Veterinary Research Communications, 18, 347–357.

Yamamoto, S.; Shida, T.; Miyaji, H.; Santsuka, H.; Fujise, H.; Mukawa, K.; Furukawa, E.; Nagae, T.; Naiki, M. (1993). Changes in serum C-reactive protein levels in dogs with various disorders and surgical traumas. Veterinary Research Communications, 17, 85–93.

Yang, J., Hamade, M., Wu, Q., Wang, Q., Axtell, R., Giri, S., & Mao-Draayer, Y. (2022). Current and Future Biomarkers in Multiple Sclerosis. International Journal of Molecular Sciences, 23(11), 1–27. https://doi.org/10.3390/ijms23115877

Publicado
18-03-2024
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Verdú Serrano, M. E., Muñoz Prieto, A., Mateo Pampliega, I., & Garcia Martínez, J. D. (2024). UTILIDAD DE LAS PROTEÍNAS DE FASE AGUDA EN EL LÍQUIDO CEFALORRAQUÍDEO CANINO PARA EL DIAGNÓSTICO DE LA MENINGOENCEFALOMIELITIS DE ORIGEN DESCONOCIDO. Anales de Veterinaria de Murcia, 38. https://doi.org/10.6018/analesvet.562071
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