Influence of Activating and Inhibitory Killer Immunoglobulin-Like Receptors (KIR) genes on the recurrence rate of ocular toxoplasmosis in Brazil

Silva, D. S. P.; Joaquim, T. E.; do Couto, A. L. Q.; Motta, J.; Ribeiro-Alves, M.; Ferreira, J. d. O.; de Moraes Sobrino, L. C. P.; Banic, D. M.; Reis Amendoeira, M. R.

doi:10.1101/2020.09.16.299446

bioRxiv · 10.1101/2020.09.16.299446

Influence of Activating and Inhibitory Killer Immunoglobulin-Like Receptors (KIR) genes on the recurrence rate of ocular toxoplasmosis in Brazil

Silva, D. S. P.·Joaquim, T. E.·do Couto, A. L. Q.·Motta, J.·Ribeiro-Alves, M.·Ferreira, J. d. O.·de Moraes Sobrino, L. C. P.·Banic, D. M.·Reis Amendoeira, M. R.

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Abstract

BackgroundRecurrence is a hallmark of ocular toxoplasmosis (OT), and conditions that influence its occurrence remain a challenge. Natural killer cells (NK) are effectors cells whose primary function is the cytotoxic activity against many parasites, including Toxoplasma gondii. Among the NK cell receptors, immunoglobulin-like receptors (KIR) deserve attention due to their high polymorphism. This study aimed to analyze the influence of KIR gene polymorphism in the course of OT infection and its association with recurrences after an active episode. MethodsNinety-six patients from the Ophthalmologic Clinic of the National Institute of Infectology Evandro Chagas (INI/Fiocruz/RJ, Brazil) were followed for up to five years. After DNA extraction, genotyping of the patients was performed by PCR-SSO utilizing Luminex equipment for reading. During follow-up, 57.4% had a recurrence. ResultsWe identified 25 KIR genotypes and found a higher frequency of genotypes 1 (31.7%) with worldwide distribution. We note that the KIR2DL2 inhibitor gene and the gene activator KIR2DS2 were more frequent in patients without recurrence (P = 0.03 and P = 0.02, respectively). Additionally, we observed one activating gene, KIR2DS1, associated with more than four times faster progression to the development of recurrent ocular toxoplasmosis than individuals without this gene (aRR = 4.6, P = 0.04). ConclusionThe KIR2DL2 and KIR2DS2 are associated as possible protection markers and the KIR2DS1 acting as a possible susceptibility marker. Additionally, the lower proportion of activating genes observed in individuals with recurrence corroborating with the hypothesis that these individuals are more susceptible to ocular toxoplasmosis recurrence (OTR).

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Silva, D. S. P., Joaquim, T. E., do Couto, A. L. Q., Motta, J., Ribeiro-Alves, M., Ferreira, J. d. O., de Moraes Sobrino, L. C. P., Banic, D. M., Reis Amendoeira, M. R.. 2020-09-16. Influence of Activating and Inhibitory Killer Immunoglobulin-Like Receptors (KIR) genes on the recurrence rate of ocular toxoplasmosis in Brazil. https://doi.org/10.1101/2020.09.16.299446

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