Anti-factor H autoantibodies in patients with lupus nephritis.

INTRODUCTION: Lupus nephritis (LN) is a disease marked by autoantibodies against complement components. Autoantibodies against negative complement regulator factor H (anti-FH) are prevalent in aHUS, are associated with deletion of factor H-related protein 1 (FHR1) gene, and have overt functional consequences. They are also observed in C3 glomerulopathies. The frequency and relevance of anti-FH in LN are poorly studied. AIM: The aim of our investigation was to screen for the presence of anti-FH and FHR1 gene deletion in a cohort of LN patients and to evaluate their association with LN activity. METHOD: ELISA test and Western blot for detection of anti-FH and FHR1 deletion were used, respectively. Patients' clinical and laboratory parameters regarding anti-FH role were processed by statistical analysis. RESULTS: Anti-FH were found at low level in a small number of LN patients - 11.7% (7/60) and were not associated with deletion of FHR1. Anti-FH did not correlate with ANA titers, anti-dsDNA, C3/C4 hypocomplementemia, eGFR, proteinuria, or active urinary sediment in LN patients. A weak correlation was found between anti-FH and anti-C3 levels. Anti-FH were linked with endocapillary proliferation and histological activity index. Four anti-FH positive patients had severe to moderate LN as per the BILAG renal score. CONCLUSIONS: Anti-FH autoantibodies are an accessory finding in LN and are more likely to manifest during the active phase of the disease. Due to their low frequency and plasma levels, they do not seem suitable for routine laboratory investigation in patients with LN.

C4d expression in focal segmental glomerulosclerosis.

BACKGROUND: There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables. MATERIAL AND METHODS: A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed. RESULTS: Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ±â€¯18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05). CONCLUSIONS: C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.

Caracterización fisicoquímica, nutricional y sensorial de dos complementos alimenticios biofortificados / Physicochemical, nutritional, and sensory characterization of two biofortified food supplements

Introducción: Las ciencias de la nutrición y los alimentos innovan en la industria elaborando productos con compuestos nutricionales que contribuyan a la resolución de problemáticas en salud pública. Pero, además de las características nutricionales, son importantes las características sensoriales, siendo un factor determinante en la aceptación de estos productos. Objetivo: Evaluar características fisicoquímicas, nutricionales y sensoriales de dos complementos alimenticios, tipo sopa y bebida achocolatada, desarrollados con biofortificación. Materiales y métodos: Se consideraron 3 fases, fase 1, preparación de dos tipos complementos alimenticios (4 formulaciones), usando la liofilización para la deshidratación de algunas materias primas, complementada con otras técnicas de procesamiento y cocción. Fase 2, evaluación sensorial por panel de expertos a través de prueba descriptiva cuantitativa y hedónica, y fase 3, caracterización bromatológica. El análisis de la información se realizó con el software Jamovi 2.3.21. mediante análisis descriptivo e inferencial. Resultados: El análisis sensorial evidenció que los alimentos que contiene corazón de res en un 5% fueron los más aceptados por los panelistas en todos los atributos sensoriales en ambos complementos. La caracterización bromatológica mostró que el complemento tipo bebida achocolatada con corazón es excelente fuente de proteína, zinc y calcio y buena fuente de hierro y vitamina E, mientras que, el complemento tipo sopa con corazón es excelente fuente de proteína, zinc, hierro, tiamina, omega 3, vitamina E y buena fuente de calcio de acuerdo con la normatividad colombiana de rotulado y etiquetado nutricional. Conclusiones: Ambos complementos con corazón mostraron una aceptación sensorial satisfactoria, presentaron una importante concentración de nutrientes, que, por su fuente natural y animal, son considerados de alta biodisponibilidad(AU)

Introduction: Nutrition and food sciences innovate in the industry by elaborating products with nutritional compounds that contribute to the resolution of public health problems. But, in addition to nutritional characteristics, sensory characteristics are important, being a determining factor in the acceptance of these products. Objective: To evaluate physicochemical, nutritional and sensory characteristics of two food supplements, soup and chocolate drink, developed with biofortification. Materials and methods: Three phases were considered: phase 1, preparation of two types of food supplements (4 formulations), using freeze-drying for dehydration of some raw materials, complemented with other processing and cooking techniques. Phase 2, sensory evaluation by expert panel through quantitative descriptive and hedonic test, and phase 3, bromatological characterization. The analysis of the information was carried out with Jamovi 2.3.21. software through descriptive and inferential analysis. Results: The sensory analysis showed that foods containing 5% beef heart were the most accepted by the panelists in all sensory attributes in both supplements. The bromatological characterization showed that the chocolate drink type supplement with heart is an excellent source of protein, zinc and calcium and a good source of iron and vitamin E, while the soup type supplement with heart is an excellent source of protein, zinc, iron, thiamine, omega 3, vitamin E and a good source of calcium in accordance with Colombian regulations on nutritional labeling and labeling. Conclusions: Both supplements with heart showed a satisfactory sensory acceptance, presented an important concentration of nutrients, which, due to their natural and animal source, are considered of high bioavailability(AU)

Implicaciones patogénicas, pronósticas y terapéuticas del complemento en las vasculitis asociadas a anticuerpo anticitoplasma de neutrófilo con afectación renal / Complement in vasculitis associated with anti-neutrophil cytoplasm antibodies with renal involvement: pathogenic, prognostic and therapeutic implications

Las vasculitis asociadas a anticuerpo anticitoplasma de neutrófilo son vasculitis primarias, que afectan a vasos pequeños de diversos órganos, entre ellos el riñón. La afectación renal, se caracteriza por presencia de glomerulonefritis con semilunas y necrosis en microscopia óptica y un patrón pauciinmune en la inmunofluorescencia. La participación del complemento en la patogenia de estas entidades se ha puesto en valor en los últimos años, inicialmente en modelos animales y posteriormente en estudios en humanos, al demostrarse la presencia de fragmentos de la vía alternativa complemento, en plasma y en orina, junto con depósitos de complemento en glomérulos y pequeños vasos de pacientes afectos por vasculitis anticuerpo anticitoplasma de neutrófilo. La presencia de complemento en estas entidades confiere peor pronóstico general y renal (AU)

ntineutrophil cytoplasmic antibody-associated vasculitides are primary vasculitides that affect small vessels in various organs, including the kidney. Renal involvement is characterized by the presence of glomerulonephritis with crescents and necrosis in light microscopy and a pauci-immune pattern in immunofluorescence. The participation of complement in the pathogenesis of these entities has been valued in recent years, initially in animal models and later in studies in humans, by demonstrating the presence of fragments of the alternative complement pathway, in plasma and urine, together with complement deposits in glomeruli and small vessels of patients affected by antineutrophil cytoplasmic antibody vasculitis. The presence of complement in these entities confers a worse general and renal prognosis (AU)

Dèficit de C2 com a diagnòstic infreqüent d’immunodeficiència / Déficit de C2 como diagnóstico infrecuente de inmunodeficiencia / C2 deficit as an infrequent diagnosis of immunodeficiency

Introducció. El dèficit de complement C2 (DC2) és una immunodeficiència que predisposa a infeccions bacterianesque poden ser greus.Cas clínic. Es presenta el cas d’un nen de 15 anys diagnosticat de DC2 en el context de tres ingressos per infeccionsinvasives causades per bacteris encapsulats, tots amb evolució favorable. Es fa l’estudi d’immunodeficiències, enquè es detecta una alteració genètica compatible amb DC2tipus 1. El pacient va seguir una evolució correcta, senseinfeccions i sense presentar manifestacions de malaltia autoimmunitària o altres complicacions, amb un calendarivacunal actualitzat.Comentari. En pacients amb infeccions bacterianes recurrents i/o invasives s’ha de fer un estudi complet d’immunodeficiències, incloent-hi els defectes del complement. Eldiagnòstic precoç permet una protecció vacunal correcta,per prevenir i reduir la incidència d’infeccions bacterianespotencialment greus o invasives, a més de vigilar l’aparicióde signes i símptomes de malaltia autoimmunitària. (AU)

Introducción. El déficit de complemento (DC2) es una inmunodeficiencia que predispone a infecciones bacterianas que pueden sergraves.Caso clínico. Se presenta el caso de un niño de 15 años diagnosticado de DC2 a raíz de tres ingresos por infecciones invasivas causadas por bacterias encapsuladas, todas ellas con evolución favorable. Se realiza el estudio de inmunodeficiencias donde se detectauna alteración genética compatible con DC2 tipo 1. El paciente hatenido una correcta evolución, sin infecciones y sin presentar manifestaciones de enfermedad autoinmune u otras complicaciones,con un calendario vacunal actualizado.Comentario. En pacientes con infecciones bacterianas recurrentesy/o invasivas se realizará un estudio completo de inmunodeficiencias incluyendo los defectos del complemento. El diagnóstico precoz permite una correcta protección vacunal para prevenir y reducirla incidencia de infecciones bacterianas potencialmente graves oinvasivas. Es importante realizar un seguimiento clínico adecuado, una prevención de infecciones mediante la vacunación y vigilar laaparición de signos y síntomas de enfermedad autoinmune. (AU)

Introduction. C2 deficiency (C2D) is an immunodeficiency that predisposes to severe bacterial infections.Case report. The case of a 15-year-old boy diagnosed with C2Dfollowing three admissions for invasive infections caused by encapsulated bacteria is presented. Immunodeficiency evaluationdisclosed a genetic alteration compatible with C2D type 1. Thepatient had a favorable clinical course, without infections andwithout presenting manifestations of autoimmune disease or othercomplications with an updated vaccination schedule.Comments. In patients with recurrent and/or invasive bacterial infections a complete immunodeficiency evaluation should be performed, including complement defects. Early diagnosis allowsproper vaccine protection to prevent and reduce the incidence ofpotentially serious or invasive bacterial infections. It is importantto have proper clinical follow-up, prevention of infections throughvaccination, and monitoring for the onset of signs and symptomsof autoimmune disease. (AU)

[Complement in vasculitis associated with anti-neutrophil cytoplasm antibodies with renal involvement: pathogenic, prognostic and therapeutic implications]. / Implicaciones patogénicas, pronósticas y terapéuticas del complemento en las vasculitis asociadas a anticuerpo anticitoplasma de neutrófilo con afectación renal.

Antineutrophil cytoplasmic antibody-associated vasculitides are primary vasculitides that affect small vessels in various organs, including the kidney. Renal involvement is characterized by the presence of glomerulonephritis with crescents and necrosis in light microscopy and a pauci-immune pattern in immunofluorescence. The participation of complement in the pathogenesis of these entities has been valued in recent years, initially in animal models and later in studies in humans, by demonstrating the presence of fragments of the alternative complement pathway, in plasma and urine, together with complement deposits in glomeruli and small vessels of patients affected by antineutrophil cytoplasmic antibody vasculitis. The presence of complement in these entities confers a worse general and renal prognosis.

Estado de vacunación en pacientes con riesgo de enfermedades invasoras por bacterias capsuladas en un hospital pediátrico de Buenos Aires / Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires

Introducción. El Ministerio de Salud contempla vacunas específicas para personas con riesgo elevado de infecciones invasoras por bacterias capsuladas (BC). En la actualidad se desconoce el cumplimiento del programa. El objetivo fue evaluar el estado de vacunación para BC en ≤ 18 años con factores de riesgo. Población y métodos. Estudio observacional, analítico, mediante encuesta a padres de ≤ 18 años con VIH, asplenia y/o déficit de complemento que concurrieron al vacunatorio de un hospital pediátrico de octubre de 2020 a septiembre de 2021. Se recabaron datos sociodemográficos y clínicos. Se evaluó el estado de vacunación para BC: neumococo, meningococo y Haemophilus influenzae b (Hib), calendario regular y antigripal. Se administró la escala de reticencia a la vacunación (ERV): rango 10-50. Se analizó la asociación entre las variables estudiadas y la vacunación para BC mediante regresión logística (OR, IC95%). Se utilizó la base datos REDCap® y STATA vs14®. Resultados. Participaron 104 sujetos, media 9,9 años (DE 4,4). Asplenia: 91,3 %, VIH: 7,6 % y déficit de complemento: 0,9 %. Nivel socioeconómico: pobreza relativa: 38,4 %, seguido por clase media: 37,5 %. Estado de vacunación completa para meningococo: 45 %, neumococo: 42 %, Hib: 97 %. El 77,9 % tenía al día el calendario regular y el 61,5 %, el antigripal. Media ERV: 41,9 (DE 3,2). No se encontraron asociaciones significativas entre las variables y el estado de vacunación para BC. Conclusiones. Un elevado porcentaje no tenía vacunación completa para BC, tampoco el calendario regular y antigripal. La confianza en la vacunación de los cuidadores fue elevada.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10­50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

Eficacia de un complemento alimenticio con colágeno hidrolizado / Efficacy of a food supplement containing hydrolyzed collagen on the improvement of clinical indices in knee osteoarthritis

La osteoartritis (OA) de rodilla es una de las principales causas de dolor y discapacidad en todo el mundo con un impacto socioeconómico importante, que afecta a la calidad de vida de los pacientes y repercute negativamente en el Sistema Nacional de Salud.El objetivo del estudio ha sido evaluar el efecto de un complemento alimenticio con péptidos de colágeno de bajo peso molecular sobre los síntomas de la OA (dolor y limitación funcional).Se realizó un ensayo clínico aleatorizado, doble ciego, controlado con placebo y paralelo de dos brazos con un periodo de seguimiento de 6 meses. El estudio incluyó a 120 pacientes con diagnóstico de gonartrosis grado 2 o 3 y artralgia, con una puntuación mínima de 50 mm (rango de 0 a 100 mm) en la escala visual analógica (EVA) de dolor. Sesenta pacientes fueron asignados al grupo experimental (GrA), que recibió 1 sobre al día del complemento alimenticio que contenía colágeno hidrolizado; el otro grupo (n=60) recibió 1 sobre al día con placebo (GrP). Los sujetos fueron evaluados en una visita inicial, antes del tratamiento (T0) y en la visita final (T1) al concluir los 6 meses del periodo de seguimiento.Ambos grupos de tratamiento fueron comparables en la visita inicial (T0). En la visita final (T1), el GrA (comparado con el GrP), experimentó una disminución estadísticamente significativa en la intensidad del dolor (escala visual analógica, EVA) y la puntuación recogida en el índice algofuncional de Lequesne. También disminuyeron en T1 las cifras de proteína C reactiva (PCR) y la velocidad de sedimentación globular (VSG) en el GrA. No se observaron efectos adversos durante el estudio.El CH mejoró los síntomas de dolor osteoarticular y la capacidad funcional en pacientes con gonartrosis, con un buen perfil de tolerancia y seguridad. (AU)

Knee osteoarthritis is a leading cause of pain and disability worldwide, having a considerable socioeconomical impact on both the health-care system and the patient quality of life.The aim of the study was to assess the effect of a food supplement containing low molecular collagen peptides in the symptoms of osteoarthritis (OA) (pain and functional limitation).A 6-month, randomized, double-blind, placebo-controlled and parallel two-arm study was conducted in 120 patients diagnosed with grade 2 or 3 OA and pain, with a minimum score of 50 mm (range 0 to 10 mm) in the visual analogic scale (VAS) for pain. The investigational product (n=60) or placebo (n=60) was taken once daily, and subjects were assessed at baseline (T0, pre-treatment) and after a follow-up period of 6 months (T1).Both groups were comparable at baseline. Compared to placebo, changes in VAS, Lequesne algofunctional index (LAI), C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) after six months of treatment, were significant lower in the group of patients taking the active product. No adverse effects were reported during the study.The HC improved the osteoarticular pain and physical function in patients with knee OA. Furthermore, it was well tolerated and satisfactory; and showed adequate results in terms of safety and acceptability of HC. The food supplement may be complementary of drug therapy in knee osteoarthritis. (AU)

Anemia hemolítica autoinmune / Autoimmune haemolytic anaemia

Las anemias hemolíticas autoinmunes (AHAI) son trastornos hematológicos adquiridos ocasionados por una destrucción periférica de eritrocitos incrementada, mediada por autoanticuerpos dirigidos frente a antígenos eritrocitarios. Se clasifican según etiología en primarias y secundarias, y según el tipo de anticuerpo detectado y temperatura de reacción en AHAI por anticuerpos calientes (AHAI-C) y AHAI por anticuerpos fríos (AHAI-F).El pilar del manejo en AHAI-C continúa siendo el tratamiento con glucocorticoides, y la adición precoz de rituximab ha demostrado buenos resultados en los últimos estudios. Las AHAI-F primarias se tratan principalmente con rituximab, solo o combinado con quimioterapia.En fase de desarrollo avanzado encontramos nuevos fármacos como los inhibidores de Syk, Ig anti-FcRn e inhibidores del complemento, que permitirán ampliar el arsenal terapéutico, especialmente en casos refractarios o recidivantes. (AU)

Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA).The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy.New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases. (AU)

[Autoimmune haemolytic anaemia]. / Anemia hemolítica autoinmune.

Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA). The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy. New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases.

Contribution of functional and quantitative genetic variants of Complement Factor H and Factor H-Related (FHR) proteins on renal pathology.

The complement system is a first line of defence against infectious, tumoral or autoimmune processes, and it is constitutively regulated to avoid excessive or unspecific activation. Factor H (FH), a most relevant complement regulator, controls complement activation in plasma and on the cellular surfaces of autologous tissues. FH shares evolutionary origin and structural features with a group of plasma proteins known as FH-Related Proteins (FHRs), which could act as FH functional antagonists. Studies in patient cohorts of atypical Haemolytic-Uraemic Syndrome (aHUS), C3 Glomerulopathy (C3G), and IgA nephropathy (IgAN), have identified rare genetic variants that give rise to severe FH and FHRs dysfunctions, and are major genetic predisposing factors. These patients also have a higher frequency of a few polymorphisms whose relevance as disease risk factors is incompletely understood. In the last years, the availability of specific reagents has allowed a more precise quantitation of FH and FHRs in plasma samples from patients and controls. These studies have revealed that some aHUS, C3G or IgAN risk polymorphisms determine mild changes in FH or FHRs levels that could somehow perturb complement regulation and favour disease pathogenesis.

Immature Platelet Fraction and Thrombin Generation: Preeclampsia Biomarkers / Fração de plaquetas imaturas e geração de trombina: Biomarcadores da pré-eclâmpsia

Abstract Preeclampsia, a human pregnancy syndrome, is characterized by elevated blood pressure and proteinuria after the 20th week of gestation. Its etiology remains unknown, and its pathophysiological mechanisms are related to placental hypoperfusion, endothelial dysfunction, inflammation, and coagulation cascade activation. Recently, the role of the complement system has been considered. This syndrome is one of the main causes of maternal and fetal mortality and morbidity. This article discusses the hypothesis of preeclampsia being triggered by the occurrence of inadequate implantation of the syncytiotrophoblast, associated with bleeding during the first stage of pregnancy and with augmented thrombin generation. Thrombin activates platelets, increasing the release of antiangiogenic factors and activating the complement system, inducing the membrane attack complex (C5b9). Immature platelet fraction and thrombin generation may be possible blood biomarkers to help the early diagnosis of preeclampsia.

Resumo A pré-eclâmpsia, uma síndrome da gestação humana, é caracterizada por elevação da pressão arterial e proteinúria patológica após a 20ª semana de gestação. Sua etiologia permanece desconhecida, e seus mecanismos fisiopatológicos estão relacionados à hipoperfusão placentária, disfunção endotelial, inflamação, e ativação da cascata de coagulação. Recentemente, o papel do sistema do complemento foi considerado. Essa síndrome é uma das principais causas de morbidade e mortalidade materna e fetal. Este artigo discute a hipótese de a pré-eclâmpsia ser desencadeada pela ocorrência da implantação inadequada do sinciciotrofoblasto, associada ao sangramento durante o primeiro trimestre da gravidez com aumento da geração de trombina. A trombina ativa plaquetas, aumentando a liberação de fatores antiangiogênicos na circulação e ativando o sistema do complemento, especialmente o complexo de ataque de membrana (C5b9). Portanto, a fração de plaquetas imaturas e a geração de trombina podem ser possíveis biomarcadores sanguíneos para auxílio no diagnóstico precoce da pré-eclâmpsia.

Aplicaciones terapéuticas del eculizumab / Therapeutic applications of eculizumab

Introducción: El eculizumab es un anticuerpo monoclonal de tipo IgG diseñado para el tratamiento de la hemoglobinuria paroxística nocturna (HPN), en el que su diana farmacológica forma parte del sistema del complemento. Su mecanismo de acción ha permitido implementarlo en el tratamiento de enfermedades huérfanas, como el síndrome urémico hemolítico atípico (SUHa), trastorno del espectro de la neuromielitis óptica (TENMO) y miastenia gravis, cuya incidencia, es baja. Asimismo, es viable en el tratamiento de Guillain Barré y el síndrome antifosfolípido catastrófico (CAPS). Objetivo: Evidenciar aplicaciones terapéuticas del eculizumab y beneficios más significativos en algunos padecimientos. Materiales y métodos: Se realizó búsqueda bibliográfica en el periodo 2010-2021, en bases de datos: Google Scholar, Science Direct, PubMed y Scielo, utilizando como palabra clave "eculizumab". Posteriormente, se afinó la búsqueda utilizando palabras claves asociadas a enfermedades tratadas con este medicamento. Resultados: Se identificó el mecanismo de acción del fármaco y su efecto sobre la patogénesis de hemoglobinuria paroxística nocturna, síndrome urémico atípico, miastenia gravis generalizada refractaria, trastorno del espectro de la neuromielitis óptica, síndromes antifosfolípidos catastrófico y Guillain-Barré. Conclusiones: El eculizumab tiene una alta seguridad y capacidad para tratar y disminuir síntomas de diversas enfermedades que involucran el sistema del complemento.

Introduction: Eculizumab is an IgG type monoclonal antibody designed to treat paroxysmal nocturnal hemoglobinuria (PNH) and its pharmacological target is a member of the complement system. Its mechanism of action has permitted its use in the treatment of orphan diseases such as atypical hemolytic uremic syndrome (aHUS), neuromyelitis optic spectrum disorder (NMOSD), and myasthenia gravis, all of which have a low incidence. Likewise, eculizumab is a viable treatment for Guillain Barré and catastrophic antiphospholipid syndrome (CAS). Objective: To describe the therapeutic applications of eculizumab and its most significant benefits in some illnesses. Materials and methods: A bibliographic search was carried out during the 2010-2021 period in Google Scholar, Science Direct, PubMed and Scielo databases using the keyword eculizumab. Then, the search was refined by using keywords associated with diseases treated with this medication. Results: The mechanism of action of the antibody and its effect on the pathogenesis of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, refractory generalized myasthenia gravis, neuromyelitis optic spectrum disorder, catastrophic antiphospholipid syndrome, and Guillain Barré were identified. Conclusions: Eculizumab has high safety and capacity in treating and diminishing symptoms of diverse illnesses, which involve the complement system.

Cumplimiento y adecuación del etiquetado de complementos alimenticios antienvejecimineto distribuidos por el canal farmacéutico / Compliance and adequacy of labelling of anti-ageing food supplements distributed through the pharmaceutical channel

JUSTIFICACIÓN: la búsqueda de un estado y aspecto óptimo de salud, la prevención de enfermedades y el retraso del envejecimiento conlleva el consumo de complementos alimenticios entre otros productos de autocuidado. La comercialización de complementos alimenticios, distribuidos tradicionalmente en farmacias, se ha diversificado, si bien el canal farmacéutico se caracteriza por asegurar la calidad y seguridad que el consumidor exige y precisa, no solamente por la selección de productos que distribuye, sino por la dispensación informada que ofrece. Se sospecha que no todos los complementos alimenticios en el mercado cumplen con la normativa vigente y por ello el consumidor puede exponerse a situaciones de riesgo por desconocimiento. OBJETIVO: este estudio tiene por objeto la verificación de la adecuación a la norma del etiquetado de una selección de complementos alimenticios antienvejecimiento. Material y métodos Se han estudiado las menciones del etiquetado de los 27 complementos alimenticios antienvejecimiento más vendidos en la provincia de S/C de Tenerife, según el volumen de ventas en los dos almacenes mayoristas de medicamentos de Santa Cruz de Tenerife (COFARTE y COFARES). Se ha comprobado su adecuación a la normativa de aplicación; Real Decreto 1487/2009, relativo a los complementos alimenticios), Reglamento (CE) Nº 1170/2009 y Reglamento (UE) Nº 1169/2011. (AU)

Claves diagnósticas en el síndrome hemolítico urémico atípico: apropósito de un caso / Diagnostic clues in atypical hemolytic uremic syndrome: a case report

El síndrome hemolítico urémico atípico (SHUa) es una entidad clínica caracterizada por anemia hemolítica no inmune, trombopenia y fallo renal, en la que las lesiones están mediadas por un proceso de microangiopatía trombótica (MAT) sistémica. Es una patología rara y cuyo origen es una desregulación del sistema del complemento debido a mutaciones en genes del mismo que llevan a una activación incontrolada de C5 y la formación del complejo de ataque de membrana. Su correcto diagnóstico permite prescribir el tratamiento basado en Eculizumab, inhibidor de C5.Se presenta el caso clínico de una paciente gestante con SHUa, con el objetivo de destacar la importancia del diagnóstico diferencial precoz para el establecimiento temprano de un tratamiento efectivo de esta patología. Se actualiza la fisiopatología, diagnóstico y estudio genético, así como el manejo terapéutico del SHUa. (AU)

Contribución de variantes funcionales y cuantitativas del Factor H y las proteínas FHRs (Factor H-Related proteins) del Complemento en patología renal / Contribution of functional and quantitative genetic variants of Complement Factor H and Factor H-Related (FHR) proteins on renal pathology

El sistema del Complemento protege al organismo frente a procesos infecciosos, tumorales y autoinmunes, y requiere una regulación muy estricta para evitar una activación excesiva o inespecífica. Entre los componentes reguladores del Complemento destaca el factor H (FH), que controla su activación en plasma y sobre la superficie de las células y tejidos propios. FH está relacionado evolutiva y estructuralmente con un conjunto de proteínas plasmáticas denominadas FHRs (FH-Related proteins), que podrían actuar como antagonistas funcionales de FH. Numerosos estudios realizados en pacientes de Síndrome Hemolítico-Urémico atípico (SHUa), glomerulopatía C3 (GC3), y nefropatía por IgA (NIgA) han identificado variantes genéticas raras que alteran sustancialmente la función del FH y las proteínas FHRs, y contribuyen de forma muy relevante a la predisposición genética a estas patologías. Estos pacientes presentan también una mayor frecuencia de determinados polimorfismos cuya repercusión en el mecanismo patogénico se está empezando a dilucidar. En los últimos años, la disponibilidad de reactivos específicos para cuantificar las proteínas FHRs de forma fiable en controles y pacientes, ha mostrado que algunos de los polimorfismos asociados a SHUa, GC3 o NIgA determinan cambios en los niveles plasmáticos de FH y proteínas FHRs, que podrían repercutir en la correcta regulación de la activación del Complemento y contribuir así al desarrollo de estas patologías. (AU)

The complement system is a first line of defence against infectious, tumoral or autoimmune processes, and it is constitutively regulated to avoid excessive or unspecific activation. Factor H (FH), a most relevant complement regulator, controls complement activation in plasma and on the cellular surfaces of autologous tissues. FH shares evolutionary origin and structural features with a group of plasma proteins known as FH-Related Proteins (FHRs), which could act as FH functional antagonists. Studies in patient cohorts of atypical Haemolytic-Uraemic Syndrome (aHUS), C3 Glomerulopathy (C3G), and IgA nephropathy (IgAN), have identified rare genetic variants that give rise to severe FH and FHRs dysfunctions, and are major genetic predisposing factors. These patients also have a higher frequency of a few polymorphisms whose relevance as disease risk factors is incompletely understood. In the last years, the availability of specific reagents has allowed a more precise quantitation of FH and FHRs in plasma samples from patients and controls. These studies have revealed that some aHUS, C3G or IgAN risk polymorphisms determine mild changes in FH or FHRs levels that could somehow perturb complement regulation and favour disease pathogenesis. (AU)

Fórmula artesanal a base de lactosuero: complemento alimenticio para niños preescolares / Artisanal whey-based formula: food supplement for preschool children

Resumen Se pretendió desarrollar una fórmula artesanal, a base de lactosuero, como complemento alimenticio para niños preescolares. Se realizó una investigación descriptiva ejecutada en tres fases: 1. Ensayos preliminares para la determinación del esquema tecnológico; 2. Evaluación fisicoquímica para la caracterización del producto y determinación de macronutrientes y 3. Evaluación sensorial donde se midió el nivel de agrado del producto final. Los datos obtenidos de los análisis se tabularon en cuatro repeticiones y se analizaron a través de estadísticas descriptivas de tendencia central y en frecuencias expresadas en tablas y gráficos mediante el programa estadístico SPSS versión 20.0. Se obtuvo que en el análisis proximal del requesón deshidratado, éste aportó por cada 100 gramos de producto: 480,28 kcal, 46,5% de proteínas, 22,36% de grasas y 23,26% de hidratos de carbono. La formulación final de la bebida constó de 2,9 g de requesón deshidratado, 3,6 g de arroz previamente cocido y 1,8 g de azúcar diluidos por cada onza preparada. Se determinó que es una fórmula hipocalórica-hiperproteica e isoosmolar, con una viscosidad de 275cP, un pH de 5,1 y con 0,291% de ácido láctico. La fórmula artesanal a base de lactosuero fue de agrado para 41 niños que participaron en el análisis sensorial. Se recomienda su uso en niños que se encuentren en condición de vulnerabilidad nutricional.

Abstract The main objective of this research was to develop an artisan formula based on whey as food supplement directed to preschool children. It was a descriptive study carried out in three phases: 1. Preliminary tests, for the determination of the technological scheme; 2. Physical-chemical evaluation, for the characterisation of the product and determination of nutrients and, 3. Sensory evaluation: the level of satisfaction of the final product measured. The data obtained from the analysis were tabulated in four repetitions and analysed through descriptive statistics of central tendency and in frequencies expressed in tables and graphs using the statistical program SPSS version 20.0. As a result, for each 100 grams of dehydrated cottage cheese this malnuprovides: 480.28 kcal, 46.5% protein; 22.36% fat and 23.26% carbohydrates. The final formulation of the drink consisted of 2.9 g of dehydrated cottage cheese, 3.6 g of previously cooked rice and 1.8 g of diluted sugar for each prepared ounce. It was determined as a hypocaloric-hyperproteic and isomolar formula, with a viscosity of 275cP, a pH of 5.1 and with 0.291% lactic acid. The artisan formula based on whey was liked by 41 children who participated in the sensory analysis. As a conclusion, it can be recommended as food supplement in children with nutritional vulnerability conditions.

Resumo O objetivo principal desta pesquisa foi desenvolver uma fórmula artesanal à base de soro de leite como suplemento alimentar direcionado a crianças pré-escolares. Foi realizado um estudo descritivo em três fases: 1. Ensaios preliminares, para determinação do esquema tecnológico; 2. Avaliação físico-química, para caracterização do produto e determinação de macronutrientes e 3. Avaliação sensorial: mediu-se o grau de satisfação do produto final. Os dados obtidos das análises foram tabulados em quatro repetições e analisados por meio de estatísticas descritivas de tendência central e em frequências expressas em tabelas e gráficos utilizando o programa estatístico SPSS versão 20.0. Como resultado da análise proximal, para cada 100 gramas de requeijão desidratado fornece: 480,28 kcal, 46,5% de proteína; 22,36% de gordura e 23,26% de carboidratos. A formulação final da bebida consistiu em 2,9 g de requeijão desidratado, 3,6 g de arroz previamente cozido e 1,8 g de açúcar diluído para cada onça preparada. O resultado concluiu que é uma fórmula hipocalórica-hiperproteica e isoosmolar, com viscosidade de 275cP, pH de 5,1 e com 0,291% de ácido lático. A fórmula artesanal à base de soro de leite foi apreciada por 41 crianças que participaram da análise sensorial. É recomendado seu uso em crianças que se encontrem em condições de vulnerabilidade nutricional.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants / Un modelo que incorpore niveles séricos de C3 del complemento podría ser de utilidad para el diagnóstico de atresia biliar en niños

Introduction: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants.Patients and methods: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups.Results: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA.Conclusions: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Introducción: Es difícil la identificación correcta de los pacientes con atresia biliar (AB), evitando los métodos diagnósticos invasivos. El objetivo de este estudio fue determinar el valor de los indicadores inmunológicos séricos para distinguir AB de otras causas de colestasis en niños.Pacientes y métodos: Se analizaron retrospectivamente los datos de niños con diagnóstico quirúrgico/histológico de AB y los datos de niños con otras causas de ictericia colestásica. Se dividió a los pacientes entre el grupo AB y el grupo de control de colestasis (CC). Se comparó entre los dos grupo los parámetros bioquímicos, principales subconjuntos linfocíticos, inmunoglobina y niveles séricos de C3 y C4 del complemento.Resultados: Se incluyó en el análisis a un total de 129 niños con AB y 63 con otras causas de colestasis (grupo control CC) con una edad media de 2,2 meses. Los niveles de células T CD3+, células T CD3+CD4+, células T prematuras y los niveles de C3 y C4 fueron significativamente más altos en el grupo AB en comparación con el grupo CC (all P < 0,05). Los análisis de correlación pareada indicaron que C3 y C4 tenían una correlación positiva significativa con -GT en el grupo AB, pero no en el grupo CC. Se determinó que cinco índices estaban significativamente asociados a AB: color de las heces, globulina, -GT, C3 y C4. Un modelo que incorporó el color de las heces, nivel de gamma-glutamil transpeptidasa, y nivel de C3 reflejó un área bajo la curva ROC (AUC) de 0,93, sensibilidad del 93% y especificidad del 83% para el diagnóstico de AB.Conclusiones: Los modelos que incorporan niveles séricos de C3 pueden ser de utilidad para diagnosticar AB de manera precisa en niños.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants.

INTRODUCTION: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. PATIENTS AND METHODS: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. RESULTS: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. CONCLUSIONS: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Papel do sistema complemento na inflamação induzida pelo veneno da serpente Bothrops jararaca

The genus Bothrops, family Viperidae, integrates a group of snakes with more than 30 species and subspecies, widely distributed in the neotropical region, occurring from southern Mexico to northern Argentina and some islands of the Caribbean. In Brazil, in 2021, they were responsible for around 70% of the more than 29,000 snakebites registered. The snake venom of this genus has a wide repertoire of molecules in its composition, such as metalloproteases, serineproteases, type C lectin, bradykininenhancing peptides (BPPs), among others. The clinical manifestations of the envenomation are complex and characterized by prominent local effects, including pain, edema, ecchymosis, blisters, abscesses and necrosis, which can progress to tissue loss, physical disability or amputation. Systemic signs can also occur, such as hemorrhage, coagulopathy, shock, and acute kidney failure. Parenteral administration of commercial polyvalent antivenom is the only scientifically validated therapeutic tool for the treatment of snakebites. However, despite the effective neutralization of the systemic effects, this treatment is still ineffective in reversing local clinical manifestations. The rapid development of local clinical manifestations is accompanied by the presence of mediators of the inflammatory process, originated from tissues damaged by the bothropic venom. Studies from our group have shown that the Bothrops jararaca venom is able to activate the complement system, suggesting that this activation may contribute to the symptoms observed in these envenomations. Considering the important role that the complement system plays in the inflammatory response, this study aimed to analyze the action of B. jararaca snake venom on the complement system and cell surface receptors involved in innate immunity. For this, we used the ex-vivo human whole blood model proposed by Mollnes et al. (2002) and recently adapted by Johnson et al. (2018). With this model, by means of immunoassays, it was evaluated the complement system activation: from the generation of anaphylatoxins and soluble terminal complement complex (sTCC /SC5b-9); the production of cytokines (IL-1β, IL-6, IL-10, IL-12p70 e TNF-α) and chemokines (IL-8, IP-10, MCP-1, MIG, RANTES); the expression of leukocyte receptors such as TLRs 2 and 4; CD14; CD11b; C3aR and C5aR; the modulation of these parameters by the use of specific inhibitors of the complement system (Cp40, PMX205). The B. jararaca venom was able to induce activation of the complement system in the human whole blood model, generating a significant increase in the production of anaphylatoxins C3a/C3a-desArg, C4a/C4a-desArg, C5a/C5a-desArg and sTCC. In leukocytes, the venom of B. jararaca induced increased expression of TLR2 and reduced expression of C5aR. The expression of CD11b, CD14, C3aR and TLR4 was not altered by the action of the venom. Inhibition of the C3 component by Cp40 resulted in a reduction to basal levels of C3a/C3a-desArg and sTCC in samples stimulated with the venom. Cp40 also caused a significant reduction in the levels of C5a/C5a-desArg, but not of C4a/C4a-desArg. Exposure to B. jararaca venom induced the production of inflammatory cytokines and chemokines such as TNF-α, IL-8, MCP1 and MIG in the human whole blood model. Treatment with Cp40 promoted a significant reduction in the production of TNF-α, IL-8 and MCP-1. The use of the C5a receptor 1 antagonist, PMX205, promoted a reduction to basal levels of TNF-α and IL8 in samples stimulated with venom. In conclusion, the data presented here suggest that the activation of the complement system, promoted by the venom of the snake B. jararaca in the human whole blood model, significantly contributes to the inflammatory process. The control of several inflammatory parameters by Cp40, an inhibitor of the C3 component, and of PMX205, a C5a receptor 1 antagonist, indicate that complement inhibition may be a possible therapeutic tool in B. jararaca envenomation.

O gênero Bothrops, família Viperidae, integra um grupo de serpentes com mais de 30 espécies e subespécies, amplamente distribuídas na região neotropical, ocorrendo desde o Sul do México até o norte da Argentina e em algumas ilhas do Caribe. No Brasil, em 2021, foram responsáveis por cerca de 70% dos mais de 29.000 acidentes ofídicos registrados. O veneno das serpentes deste gênero possui amplo repertório de moléculas em sua composição, como metaloproteases, serinoproteases, lectina do tipo C, peptídeos potenciadores de bradicinina (BPPs), entre outras. As manifestações clínicas do envenenamento são complexas e caracterizadas por efeitos locais proeminentes, incluindo dor, edema, equimose, bolhas, abcessos e necrose, que podem evoluir para perda tecidual, incapacidade física ou amputação. Sinais sistêmicos também podem ocorrer, tais como hemorragia, coagulopatia, choque e insuficiência renal aguda. A administração parenteral do antiveneno polivalente comercial constitui o único recurso terapêutico cientificamente validado para o tratamento dos acidentes ofídicos. Contudo, apesar da efetiva neutralização dos efeitos sistêmicos, esse tratamento ainda se mostra ineficiente na reversão das manifestações clínicas locais. O rápido desenvolvimento das manifestações clínicas locais é acompanhado pela presença de mediadores do processo inflamatório, originados a partir de tecidos lesados pelo veneno botrópico. Estudos do nosso grupo mostraram que o veneno da Bothrops jararaca é capaz de ativar o sistema complemento, sugerindo que essa ativação possa contribuir para os sintomas observados nesses envenenamentos. Considerando o importante papel que o sistema complemento desempenha na reposta inflamatória, o presente estudo teve como objetivo analisar a ação do veneno da serpente B. jararaca sobre o sistema complemento e receptores de superfície celular envolvidos na imunidade inata. Para isto, utilizamos o modelo ex-vivo de sangue total humano, proposto por Mollnes e colaboradores (2002) e, recentemente, adaptado por Johnson e colaboradores (2018). Com este modelo, por meio de imunoensaios, foram avaliadas a ativação do sistema complemento: a partir da geração de anafilatoxinas e complexo terminal do complemento solúvel (sTCC /SC5b-9); produção de citocinas (IL-1β, IL-6, IL-10, IL12p70 e TNF-α) e quimiocinas (IL-8, IP-10, MCP-1, MIG, RANTES); expressão de receptores de leucócitos, como TLRs 2 e 4; CD14; CD11b; C3aR e C5aR; modulação destes parâmetros pelo uso de inibidores específicos do sistema complemento (Cp40, PMX205). O veneno da B. jararaca foi capaz de induzir ativação do sistema complemento no modelo de sangue total humano, gerando aumento significativo na produção das anafilatoxinas C3a/C3a-desArg, C4a/C4a-desArg, C5a/C5a-desArg e sTCC. Nos leucócitos, o veneno da B. jararaca induziu aumento da expressão de TLR2 e redução da expressão de C5aR. A expressão de CD11b, CD14, C3aR e TLR4 não foi alterada pela ação do veneno. A inibição do componente C3 pelo Cp40 resultou na redução para níveis basais de C3a/C3a-desArg e do sTCC nas amostras estimuladas com o veneno. O Cp40 também causou uma redução significativa nos níveis de C5a/C5a-desArg, mas não de C4a/C4a-desArg. A exposição ao veneno da B. jararaca induziu a produção de citocinas e quimiocinas inflamatórias como TNF-α, IL-8, MCP-1 e MIG no modelo de sangue total humano. O tratamento com Cp40 promoveu uma redução significativa na produção de TNF-α, IL- 8 e MCP-1. O uso do antagonista do receptor 1 de C5a, PMX205, promoveu redução para níveis basais de TNF-α e IL-8 em amostras estimuladas com veneno. Em conclusão, os dados aqui apresentados sugerem que a ativação do sistema complemento, promovida pelo veneno da serpente B. jararaca no modelo de sangue total humano, contribui significativamente para o processo inflamatório. O controle de vários parâmetros inflamatórios pelo uso do Cp40, inibidor do componente C3, e do PMX205, antagonista do receptor 1 de C5a, indicam que a inibição do complemento possa ser uma possível ferramenta terapêutica no envenenamento por B. jararaca.