Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patients.

Human immunodeficiency virus-1 (HIV-1) and Toxoplasma gondii can invade the central nervous system and affect its functionality. Advanced HIV-1 infection has been associated with defects in immune response to T. gondii, leading to reactivation of latent infections and development of toxoplasmic encephalitis. This study evaluates relationship between changes in immune response to T. gondii and neurocognitive impairment in HIV-1/T. gondii co-infected patients, across different stages of HIV-1 infection. The study assessed the immune response to T. gondii by measuring cytokine production in response to parasite antigens, and also neurocognitive functions by performing auditory and visual P300 cognitive evoked potentials, short term memory (Sternberg) and executive function tasks (Wisconsin Card Sorting Test-WCST) in 4 groups of individuals: HIV-1/T. gondii co-infected (P2), HIV-1-infected/T. gondii-non-infected (P1), HIV-1-non-infected/T. gondii-infected (C2) and HIV-1-non-infected/T. gondii-non-infected (C1). Patients (P1 and P2) were grouped in early/asymptomatic (P1A and P2A) or late/symptomatic (P1B/C and P2B/C) according to peripheral blood CD4+ T lymphocyte counts (>350 or <350/µL, respectively). Groups were compared using T-student or U-Mann-Whitney tests as appropriate, p<0.05 was considered as significantly. For P300 waves, HIV-1-infected patients (P1) had significantly longer latencies and significantly smaller amplitudes than uninfected controls, but HIV-1/T. gondii co-infected patients (P2) had significantly longer latencies and smaller amplitude than P1. P1 patients had significantly poorer results than uninfected controls in Sternberg and WCST, but P2 had significantly worse results than P1. HIV-1 infection was associated with significantly lower production of IL-2, TNF-α and IFN-γ in response to T. gondii from early/asymptomatic stages, when comparing P2 patients to C2 controls. These findings may indicate impairment in anti-parasitic response in co-infected patients, facilitating early limited reactivation of the parasitic latent infection, therefore creating cumulative damage in the brain and affecting neurocognitive functions from asymptomatic stages of HIV-1 infection, as suggested by defects in co-infected patients in this study.

Respuesta inmunitaria anti-SARS-CoV-2: Infección Naturalvs. Vacunación / Anti-SARS-CoV-2 immune response: natural infection vs vaccination

Este trabajo es una revisión bibliográfica que compara la inmunidad anti-SARS-CoV-2 inducida por la infección natural y la inducida por vacunación, para entenderlas particularidades de la respuesta en cada caso, así como sus ventajas y desventajas. Se escogieron artículos que reportaran la medición de concentración de anticuerpos séricos, determinantes de inmunidad celular y/o evolución clínica de los pacientes. Se encontró que: A) Los pacientes recuperados de una infección por SARS-CoV-2 presentaron una respuesta mayor y más heterogénea de anticuerpos y células B de memoria que los pacientes vacunados, con un mayor número de linfocitos TCD4+, que cooperan con la diferenciación de linfocitos B y con la producción de anticuerpos neutralizantes. B) La vacunación previene la tormenta de citocinas asociada a la infección natural. C) Dos dosis de una vacuna basada en ARN mensajero logran una concentración de anticuerpos de clase IgG prácticamente igual a la de los pacientes severamente enfermos, pero sin el daño a los nódulos linfáticos asociado a la infección natural. D) Se puede aumentar el número de linfocitos B administrando dosis de refuerzo de la vacuna. Si bien, tanto la vacunación como la infección natural generan respuestas anti-SARS-CoV-2 significativas, la vacunación es el método más seguro para proteger a la población, pues evita el riesgo a la inmunopatología y a la mortalidad asociados con la infección natural. Más aún, la inmunidad híbrida (aquella que adquieren los pacientes que superaron la infección natural y fueron después vacunados) induce una producción de anticuerpos capaces de neutralizar por completo al SARS-CoV-2(AU)

This work is a bibliographic review that comparesanti-SARS-CoV-2 inmmune response induced by natural infección with that induced by vaccination, to understand theparticularities of each response, as well as their advantages and disadvantages. Research articles that reported levels of antibodies in serum, determinants of cellular inmmunity and/or clinical evolution of patients were chosen. It was found that: A) Pacients previously infected with SARS-CoV-2 presented a larger and more heterogeneous response of antibodies and memory B cells than vaccined patients, with a larger number of CD4+T cells that cooperate with the differentiation of B cells and production of neutralizing antibodies. B) Vaccination prevents the cytokine storm associated with natural infection. C) Two doses of an mRNA vaccine induced an IgG concentration nearly equal to severe ill patients but without the damage to lymph nodes associated with natural infection. D) B cell levels can be increased by giving booster doses of the vaccine. Althought both vaccination and natural infection generate significant anti-SARS-CoV-2 immune responses, vaccination is the safest method to protect general population, because it avoids the risk of immunopathology and mortality associated with natural infection. Futhermore, hybrid immunity (thatadquired by patients who overcame the natural infection and were later vaccinated), induces production of antibodies capable of completely neutralizing SARS-CoV-2(AU)

Alteraciones en la producción de citosinas en respuesta a Toxoplasma gondii aparecen desde las etapas tempranas en pacientes co-infectados con VIH-1 / Alterations in the production of cytokines in response to Toxoplasma gondii appear from early stages in patients co-infected with HIV-1

Resumen Tanto el Virus de Inmunodeficiencia Humana-1 (VIH-1), como el protozoo Toxoplasma gondii son capaces de infectar al ser humano e invadir su sistema nervioso central (SNC). En individuos inmunocompetentes T. gondii causa infecciones crónicas, generalmente asintomáticas; sin embargo, la inmunodeficiencia asociada a etapas avanzadas de la infección por VIH-1, se relaciona con la pérdida del control de la infección parasitaria latente y enfermedades graves a nivel del SNC, como encefalitis toxoplásmica. Este trabajo tuvo como objetivo evaluar la evolución de la respuesta inmunitaria contra T. gondii en pacientes co-infectados con VIH-1, en distintas etapas de la infección viral. La respuesta contra T. gondii se evaluó a través de la producción in vitro de citosinas en respuesta a antígenos parasitarios, en individuos con serología positiva para VIH-1 y negativa para T. gondii (P1), positiva para VIH-1 y T. gondii (P2), negativa para VIH-1 y T. gondii (C1) y negativa para VIH-1 y positiva para T. gondii (C2). Los pacientes (P1 y P2) se agruparon en tempranos/asintomáticos (P1A, P2A) o tardíos/sintomáticos (P1B/C, P2B/C) de acuerdo a su recuento de linfocitos T CD4+ en sangre periférica (>350 o <350 células/μL, respectivamente). La infección por VIH-1, desde etapas tempranas, se asoció con una producción de IL-2, TNF-α e IFN-γ en respuesta a T. gondii significativamente menor. Estos defectos pueden entorpecer la respuesta anti-T. gondii en pacientes co-infectados, aumentando la posibilidad de reactivación de las infecciones latentes, lo que representa un riesgo para la integridad y funcionalidad del SNC.

Abstract Both HIV-1 and Toxoplasma gondii are able to invade central nervous system and affect its functionality. Advanced HIV-1 infection has been associated with defects in immune response to T. gondii, leading to reactivation of latent infections and the appearing of toxoplasmic encephalitis. This study evaluated changes in the immune response to T. gondii in different stages of HIV infection. Immune response to T. gondii was assessed studying cytokine production in response to parasite antigens in HIV-1-infected/T. gondii-noninfected (P1), HIV-1/T. gondii co-infected (P2), HIV-1-non-infected/T. gondiinon-infected (C1) and HIV-1-non-infected/T. gondii-infected (C2) individuals. Patients (P1 and P2) were divided in early/asymptomatic (P1A, P2A) or late/symptomatic (P1B/C, P2B/C) according to peripheral blood CD4+ T lymphocyte counts (>350 or <350/μL, respectively). The HIV-1 infection, from early/asymptomatic stages, was associated with significant lower production of IL-2, TNF-α and IFN-γ in response to T. gondii, when P2 patients were compared with C2 controls. These early defects may impair anti-parasitic response in co-infected patients, allowing to reactivation of parasitic latent infection, enhancing the risk of CNS damage and impairment of neurocognitive functions.

The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance.

BACKGROUND: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. METHODS: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

Reproducibilidad en la lectura de un set de placas de citología cérvico-uterinas en cuatro centros especializados de Medellín, Antioquia / Reproducibility of reading a set of cervical cytology smears in four specialized centers in Medellin, Antioquia

OBJETIVO: evaluar el grado de reproducibilidad en la lectura de placas de citología cérvico-uterina entre cuatro centros de lectura especializados de la ciudad de Medellín, Colombia. METODOLOGIA: 181 placas de citología cérvico-uterina provenientes de un estudio de prevalencia de anormalidades citológicas en Pueblorrico, Antioquia, se sometieron a lectura en cuatro centros especializados de Medellín. Se le pidió a cada centro que realizara una lectura rutinaria manteniendo el estudio en ciego por medio de recodificación de las placas, evitando que se filtrara información entre centros. Se calculó la concordancia general y el índice kappa de Fleiss. RESULTADOS : de las 181 placas, sólo en 55 placas los 4 centros concordaron en el resultado, obteniéndose un porcentaje de concordancia global del 30% y un índice kappa global de 0,31. Según la escala de Fleiss, se observó una baja reproducibilidad en la lectura de las placas citológicas entre los cuatro centros involucrados en el estudio. La concordancia por pares de centros presentó índices de kappa entre 0,3 a 0,7. CONCLUSION:existe una alta variabilidad en la interpretación de los resultados citológicos entre los centros estudiados. Es necesario implementar procesos de entrenamiento y unificación de criterios de lecturas de la citología cervical en nuestro medio.

OBJECTIVE: to assess the degree of reproducibility in the reading of cervical cytology smears among four specialized reading centers at Medellin, Colombia.. METHODOLOGY: 181 cervical cytology smears from a study on the prevalence of cytological abnormalities in Pueblorrico, a town located in the southwestern region of the state of Antioquia in Colombia, were re-read by four specialized centers in Medellin. Each center was asked to conduct a blind routine reading of the smears to avoid disclosure of information between centers. The reproducibility was measured by percentage agreement and kappa. RESULTS :of 181 smears only 55 matched across all 4 centers, with an overall concordance rate of 30% and an overall kappa of 0.31. According to Fleiss scale, poor reproducibility was observed. The concordance between pairs of centers ranged between 0.3 y 0.7. DISCUSSION:there is a high variability in the interpretation of cytological results among centers in Medellin. It is necessary to implement training processes and to unify readings for cervical cytology criteria.