Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci
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Resumen
Objetivo. Evaluar la asociación entre los genotipos de 5-HT y la presencia de anticuerpos séricos en pacientes con PANDAS.
Método. Comparamos la frecuencia de genotipos de 5-HT y los títulos de anticuerpos anti-estreptococo, antineurales y antienolasa en suero de 56 pacientes con PANDAS y 20 controles sanos de México y Cuba.
Resultados. Los títulos de anticuerpos antienolasa y antiestreptococo fueron mayores en pacientes con PANDAS en comparación con los controles. El título de anticuerpos antienolasa y antineural aumentó de acuerdo con el polimorfismo de los pacientes con PANDAS de la siguiente manera: LL >SL >SS.
Discusión y conclusión. Éste es el primer estudio que evalúa la asociación entre los genotipos de 5-HTTLPR y anticuerpos en pacientes con PANDAS. Las asociaciones entre polimorfismos de genes serotoninérgicos y la respuesta inmune podrían proporcionar información sobre la interacción entre ambos sistemas. Nuestros resultados sugieren una asociación entre el alelo S y niveles altos de anticuerpos en pacientes con PANDAS.
Referencias
Ahern, G. P. (2011). 5-HT and the immune system. Current Opinion in Pharmacology, 11(1), 29-33. doi: 10.1016/j.coph.2011.02.004
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Publishing, Inc.
Bastani, B., Arora, R. C., & Meltzer, H. Y. (1991). Serotonin uptake and imipramine binding in the blood platelets of obsessive-compulsive disorder patients. Biological Psychiatry, 30(2), 131-139. doi: 10.1016/0006-3223(91)90166-J
Bengel, D., Greenberg, B. D., Corá-Locatelli, G., Altemus, M., Heils, A., Li, Q., & Murphy, D. L. (1999). Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder. Molecular Psychiatry, 4(5), 463-466. doi: 10.1038/sj.mp.4000550
Billett, E. A., Richter, M. A., King, N., Heils, A., Lesch, K. P., & Kennedy, J. L. (1997). Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Molecular Psychiatry, 2(5), 403-406. doi: 10.1038/sj.mp.4000257
Cabrera-Mendoza, B., Genis-Mendoza, A. D., & Nicolini, H. (2019). Diagnosis in PANDAS: An update. Current Psychiatry Research and Reviews, 15(4), 237-247. doi: 10.2174/2666082215666190917161514
Camarena, B., Rinetti, G., Cruz, C., Hernández, S., de la Fuente, J. R., & Nicolini, H. (2001). Association study of the serotonin transporter gene polymorphism in obsessive–compulsive disorder. International Journal of Neuropsychopharmacology, 4(3), 269-272. doi: 10.1017/S1461145701002516
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., ... Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT Gene. Science, 301(5631), 386-389. doi: 10.1126/science.1083968
Caspi, A., Vishne, T., Sasson, Y., Gross, R., Livne, A., & Zohar, J. (2008). Relationship between childhood sexual abuse and obsessive-compulsive disorder: Case control study. Israel Journal of Psychiatry and Related Sciences, 45(3), 177-182.
Contreras, J., Hernández, S., Quezada, P., Dassori, A., Walss-Bass, C., Escamilla, M., & Raventos, H. (2010). Association of serotonin transporter promoter gene polymorphism (5-HTTLPR) with depression in Costa Rican schizophrenic patients. Journal of Neurogenetics, 24(2), 83-89. doi: 10.3109/01677060903583994
Gudayol-Ferré, E., Herrera-Guzmán, I., Camarena, B., Cortés-Penagos, C., Herrera-Abarca, J. E., Martínez-Medina, P., … Guàrdia-Olmos, J. (2010). The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder. Journal of Affective Disorders, 127(1-3), 343-351. doi: 10.1016/j.jad.2010.06.002
Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66(6), 2621-2624. doi: 10.1046/j.1471-4159.1996.66062621.x
Hu, X., Lipsky, R. H., Zhu, G., Akhtar, L. A., Taubman, J., Greenberg, B. D., … Goldman, D. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. The American Journal of Human Genetics, 78(5), 815-826. doi: 10.1086/503850
Jaiswal, P., Mohanakumar, K. P., & Rajamma, U. (2015). Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders. Neuroscience & Biobehavioral Reviews, 55, 413-431. doi: 10.1016/j.neubiorev.2015.05.013
Lin, P. (2007). Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive–compulsive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 31(3), 683-689. doi: 10.1016/j.pnpbp.2006.12.024
Mak, L., Streiner, D. L., & Steiner, M. (2015). Is serotonin transporter polymorphism (5-HTTLPR) allele status a predictor for obsessive-compulsive disorder? A meta-analysis. Archives of Women’s Mental Health, 18(3), 435-445. doi: 10.1007/s00737-015-0526-z
Marazziti, D., Mucci, F., & Fontenelle, L. F. (2018). Immune system and obsessive-compulsive disorder. Psychoneuroendocrinology, 93, 39-44. doi: 10.1016/j.psyneuen.2018.04.013
Margoob, M. A., & Mushtaq, D. (2011). Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link? Indian Journal of Psychiatry, 53(4), 289-299. doi: 10.4103/0019-5545.91901
Matsunaga, H., Maebayashi, K., & Kiriike, N. (2008). A review of the researches focusing on the heterogeneity of obsessive-compulsive disorder and its potential subtypes. Seishin Shinkeigaku Zasshi = Psychiatria Et Neurologia Japonica, 110(3), 161-174.
Mössner, R., & Lesch, K. P. (1998). Role of serotonin in the immune system and in neuroimmune interactions. Brain, Behavior, and Immunity, 12(4), 249-271. doi: 10.1006/brbi.1998.0532
Moya, P. R., Wendland, J. R., Rubenstein, L. M., Timpano, K. R., Heiman, G. A., Tischfield, J. A., … Murphy, D. L. (2013). Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette’s disorder. Movement Disorders, 28(9), 1263-1270. doi: 10.1002/mds.25460
Nicholson, T. R. J., Ferdinando, S., Krishnaiah, R. B., Anhoury, S., Lennox, B. R., Mataix-Cols, D., … Heyman, I. (2012). Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: Cross-sectional study. British Journal of Psychiatry, 200(5), 381-386. doi: 10.1192/bjp.bp.111.092007
Nicolini, H., Cruz, C., Camarena, B., Páez, F., & de la Fuente, J. R. (1999). Understanding the genetic basis of obsessive-compulsive disorder. CNS Spectrums, 4(5), 32-34. doi: 10.1017/S1092852900011706
Nicolini, H., Herrera, K., Páez, F., de Carmona, M. S., Orozco, B., Lodeiro, G., & de la Fuente, J. R. (1996). Traducción al español y confiabilidad de la Escala Yale-Brown para el trastorno obsesivo-compulsivo. Salud Mental, 19(3), 13-16.
Nicolini, H., López, Y., Genis-Mendoza, A. D., Manrique, V., Lopez-Canovas, L., Niubo, E., … Santana, D. (2015). Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders. Actas Españolas de Psiquiatria, 43(2), 35-41.
Orefici, G., Cardona, F., Cox, C. J., & Cunningham, M. W. (2016). Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). In: Ferretti J. J, Stevens D. L, Fischetti V. A, (Ed.). Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center.
O’Connell, P. J., Wang, X., Leon-Ponte, M., Griffiths, C., Pingle, S. C., & Ahern, G. P. (2006). A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood, 107(3), 1010-1017. doi: 10.1182/blood-2005-07-2903
Perez, M., Brown, J. S., Vrshek-Schallhorn, S., Johnson, F., & Joiner Jr, T. E. (2006). Differentiation of obsessive-compulsive-, panic-, obsessive-compulsive personality-, and non-disordered individuals by variation in the promoter region of the serotonin transporter gene. Journal of Anxiety Disorders, 20(6), 794-806. doi: 10.1016/j.janxdis.2005.09.001
Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl 20), 22-33.
Sheehan, D. V., Sheehan, K. H., Shytle, R. D., Janavs, J., Bannon, Y., Rogers, J. E., … Wilkinson, B. (2010). Reliability and validity of the mini international neuropsychiatric interview for children and adolescents (MINI-KID). The Journal of Clinical Psychiatry, 71(03), 313-326. doi: 10.4088/JCP.09m05305whi
Singer, H. S., Mascaro-Blanco, A., Alvarez, K., Morris-Berry, C., Kawikova, I., Ben-Pazi, H., … Cunningham, M. W. (2015). Neuronal antibody biomarkers for Sydenham’s chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection. PloS One, 10(3), e0120499. doi: 10.1371/journal.pone.0120499
Sinopoli, V. M., Burton, C. L., Kronenberg, S., & Arnold, P. D. (2017). A review of the role of serotonin system genes in obsessive-compulsive disorder. Neuroscience & Biobehavioral Reviews, 80, 372-381. doi: 10.1016/j.neubiorev.2017.05.029
Swedo, S. E., Leonard, H. L., & Rapoport, J. L. (2004). The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: Separating fact from fiction. Pediatrics, 113(4), 907-911. doi: 10.1542/peds.113.4.907
Ulloa, R. E., De la Peña, F., Higuera, F., Palacios, L., Nicolini, H., & Ávila, J. (2004). Estudio de validez y confiabilidad de la versión en español de la Escala Yale-Brown del trastorno obsesivo-compulsivo para niños y adolescentes. Actas Españolas de Psiquiatría, 32(4), 216-221.
Zhang, Y. W., Gesmonde, J., Ramamoorthy, S., & Rudnick, G. (2007). Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder. Journal of Neuroscience, 27(40), 10878-10886. doi: 10.1523/JNEUROSCI.0034-07.2007
