Outbreak of Hemagglutinating encephalomyelitis coronavirus infection in pigs in Argentina. Pathological, virological, molecular and serological study

Se describe un brote en lechones lactantes caracterizado por vómitos, signos nerviosos, emaciación y alta mortalidad producida por el coronavirus de la encefalomielitis hemaglutinante del cerdo (PHE-CoV). Se realizó la confirmación diagnóstica por medio de estudios histopatológicos, inmunohistoquímicos (IHQ) y de biología molecular (RT-PCR y secuenciación de los amplicones). Los hallazgos más salientes fueron: encefalitis o meningoencefalomielitis no supurativa y ganglioneuritis, presencia de manguitos perivasculares con degeneración neuronal de los plexos de Meissner y Auerbach en la región pilórica del estómago. Mediante IHQ se observó inmunomarcación en el citoplasma de las neuronas del tallo cerebral y del ganglio trigémino. Mediante RT-PCR de muestras de tejido nervioso IHQ positivas se visualizó un producto de igual pb que el primer de pancoronavirus utilizado. La secuenciación del amplicón se correspondió en un 95% con las secuencias reportadas de la cepa VW572 de PHE-CoV (GenBank). Se realizó un estudio epidemiológico preliminar mediante la prueba serológica de inmunofluorescencia indirecta (IFI), en 9 granjas. Sobre el total de las granjas estudiadas 6 fueron positivas; siendo la granja motivo del trabajo, la única que manifestó entidad clínica. Estos resultados preliminares indican la presencia de una infección endémica por PHE-CoV en la República Argentina, en la mayoría de los casos en forma subclínica. Este trabajo constituye la primera comunicación de un brote de PHE-CoV en la Argentina y en Sudamérica, considerándosela como una enfermedad emergente.An outbreak of vomiting, wasting and nervous signs in piglets less than 3 weeks old caused by porcine hemagglutinating encephalomyelitis coronavirus (PHECoV) infection is described. The etiological diagnosis was made by histopathology, immunohistochemistry (IHC), RTPCR and genomic sequence (GS) studies. Nonsuppurative encephalomyelitis or meningoencephalomyelitis, ganglioneuritis and perivascular cuffing with neuronal degeneration on intramural plexus of stomach were the main changes. By IHC, PHE-CoV was detected in neurons of the brainstem and in the trigeminal ganglion which correlates with the RT-PCR products detected in the same samples. Sequence analysis of PCR amplicons showed 95% correspondence with the WW572 strain of PHE-CoV virus from GenBank reference. A preliminary epidemiological study was performed by indirect immunofluorescence antibody test (IFAT) in 9 farms. Results of serological survey to detect antibodies against PHE-CoV by IFAT showed 6 positive farms. However, only the farm under study reported clinical signs. These preliminary results showed that PHE-CoV infection is widespread in Argentina in subclinical form, however new outbreaks might occur particularly in naive farms. The above results confirmed PHE-CoV infection as newly recognized emerging disease of pigs in Argentina and South America.Facultad de Ciencias Veterinaria

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection

Abstract Background Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. Methods To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF’17 classification, was identified. Results We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. Conclusions Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. Trial registration Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01

B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs). Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization. Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable. Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting

Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought

Extreme drought impacts have been underestimated in grasslands and shrublands globally

Altres Ajuts: Fundación Ramón Areces grant CIVP20A6621Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought

Extreme drought impacts have been underestimated in grasslands and shrublands globally

Climate change is increasing the frequency and severity of short-term (~1 y) drought events—the most common duration of drought—globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function—aboveground net primary production (ANPP)—was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought