Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein

BACKGROUND: Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in particularly in relation to its deficiency. Due to its involvement in brain diseases, identifying the source of MBL in CSF is important. Analysis of cerebrospinal fluid (CSF) can provide data that discriminates between blood-, brain-, and leptomeninges-derived proteins. To detect the source of MBL in CSF we need to consider three variables: the molecular size-dependent concentration gradient between CSF and blood, the variation in transfer between blood and CSF, and the CSF MBL concentration correlation with the albumin CSF/serum quotient (QAlb), i.e., with CSF flow rate. METHODS: MBL was assayed in samples of CSF and serum with an ELISA, coated with anti MBL antibodies. Routine parameters such as albumin-, immunoglobulin- CSF/serum quotients, oligoclonal IgG and cell count were used to characterize the patient groups. Groups comprised firstly, control patients without organic brain disease with normal CSF and normal barrier function and secondly, patients without inflammatory diseases but with increased QAlb, i.e. with a blood CSF barrier dysfunction. RESULTS: MBL concentration in CSF was at least five-fold higher than expected for a molecular-size-dependent passage from blood. Secondly, in a QIgM/QAlb quotient diagram (Reibergram) 9/13 cases showed an intrathecal fraction in some cases over 80% of total CSF MBL concentration 3) The smaller inter-individual variation of MBL concentrations in CSF of the control group (CV = 66%) compared to the MBL concentrations in serum (CV = 146%) indicate an independent source of MBL in CSF. 4) The absolute MBL concentration in CSF increases with increasing QAlb. Among brain-derived proteins in CSF only the leptomeningeal proteins showed a (linear) increase with decreasing CSF flow rate, neuronal and glial proteins are invariant to changes of QAlb. CONCLUSIONS: MBL in CSF is predominantly brain-derived and all results pointed to the leptomeningeal cells as the source of the protein. The evaluation of this protein requires the interpretation of its absolute concentrations in CSF as a function of the albumin quotient, QAlb. This recognition of MBL in brain cells opens a new field of discussion about the function of the innate immune response in CNS in cases of acute and chronic neurological diseases

CSF/serum quotient graphs for the evaluation of intrathecal C4 synthesis

<p>Abstract</p> <p>Background</p> <p>Cerebrospinal fluid (CSF)/serum quotient graphs have been used previously to determine local synthesis in brain of immunoglobulins and C₃complement component. The aim of this study was to use the same technique to construct quotient graphs, or Reibergrams, for the beta globulin C₄and to evaluate the method for assessing intrathecal synthesis in neurological disease.</p> <p>Methods</p> <p>The constants in the previously-defined Reibergram for immunoglobulin IgA were used to calculate the CSF/serum quotient for C₄. CSF and serum were analyzed for C₄, IgA and albumin from a total of 12 patients with meningoencephalitis caused by encapsulated microorganisms and 10 subjects without infections or inflammatory neurological disease, some of which had dysfunction of the blood-CSF barrier,</p> <p>Results</p> <p>The formula and C₄Reibergram with the constants previously found for IgA, determined the intrathecal C₄synthesis in CSF. The intrathecal C₄fraction in CSF (C₄loc in mg/l) was compared to the C₄-Index (fraction of CSF: serum for C ₄/fraction of CSF: serum for albumin). There was a significant correlation between the two formulae. The CSF/Serum quotient graph was superior for detecting intrathecal synthesis of C₄under variable conditions of blood-CSF barrier permeability.</p> <p>Conclusion</p> <p>The C₄Reibergram can be used to quantify the intrathecal synthesis of this component of the complement system in different infectious diseases of the central nervous system and is especially useful for patients with blood-brain barrier dysfunction.</p

Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series

<p>Abstract</p> <p>Introduction</p> <p>Eosinophilic meningitis, a potentially fatal disease caused by <it>Angiostrongylus cantonensis</it>, is considered an emerging infectious disease.</p> <p>Case presentation</p> <p>Three Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by <it>Angiostrongylus cantonensis </it>were studied. Serum immunoglobulin A (IgA), IgM, IgG, and complements C3c and C4 levels were quantified by using an immunodiffusion technique. Immunoglobulin E in serum was quantified by nephelometry and mannose-binding lectin by time-resolved fluorometry. Mannose-binding lectin deficiency was observed in the three patients. The first patient showed a reduction in the levels of IgA and IgM and an increase in the values of IgE and C4. The second patient showed a reduction in mannose-binding lectin level with increased IgG, C4 and IgE levels, and the third patient showed a decrease in mannose-binding lectin level and increased levels of IgM and complement C3c as well as a low level of C4.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of mannose-binding lectin deficiency associated with <it>Angiostrongylus cantonensis </it>meningoencephalitis in children, and it may contribute to the understanding of the participation of this component of the lectin pathway in the development of the disease.</p

Neuroimmunology of meningoencephalitis by Cryptococcus neoformans. A case report

Introduction: Meningitis/meningoencephalitis is a non-frequent central nervous system infection produced by Cryptococcus neoformans. Objective: To show the neuroimmunological response using reibergram in a patient with chronic meningoencephalitis due to Cryptococcus neoformans. Case presentation: Serum and cerebrospinal fluid IgA, IgM, IgG and albumin levels were quantified in a patient suffering from the disease by means of five lumbar punctures during her evolution; the results were plotted in their corresponding reibergram. Syntheses of at least two intrathecal major immunoglobulin were confirmed. A percent bigger of IgG intrathecal synthesis was observed. There is no blood-brain barrier dysfunction. Conclusion: Intrathecal immunoglobulin synthesis and blood-brain barrier situation constitute key element in the neuro-inflammation diagnosis.Keywords: Cryptococcus neoformans, Neuroimmunology, reibergram,   chronic meningoencephalitis.</p

Meningoencefalitis eosinofílica por Angiostrongylus cantonensis y variables meteorológicas

Introducción: Angiostrogylus cantonensis es un helminto que vive en las arterias pulmonares de dos especies de ratas: Rattus rattus y Rattus norvergicus. El hombre es un hospedero accidental que se infecta al ingerir las larvas de tercer estadio a través de vegetales o frutas mal lavados y por la ingestión de diferentes especies de moluscos, que constituyen los hospederos intermediarios. Objetivo: Caracterizar las condiciones de humedad, temperatura y lluvia caída en las zonas donde se reportaron los pacientes y su vinculación con la aparición de los casos de meningoencefalitis eosinofílica por Angiostrongylus cantonensis. Material y métodos: Se estudiaron 34 pacientes diagnosticados con esta enfermedad que fueron ingresados en el Hospital Pediátrico San Miguel del Padrón, en La Habana, Cuba, en el período de enero de 1991 hasta enero del 2014. Para la obtención de los datos correspondientes a las variables meteorológicas se acudió con la fecha de ingreso de los enfermos a los registros diarios y mensuales del Instituto de Meteorología. Se calcularon los coeficientes de correlación para cada variable meteorológica y el número de casos y se ajustaron las rectas de regresión correspondientes. Resultados: Los enfermos se concentraron en períodos en que la humedad promedio anual osciló entre 75 y 76 %, mientras que la humedad ambiental varío entre 65 y 80 %. La probabilidad de encontrar casos enfermos es mayor entre los años con lluvia anual promedio entre 68 y más de 120 mm. Para la temperatura, la correlación fue negativa, a medida que se registra un aumento de temperatura hay una disminución del número de enfermos. Conclusiones: El mayor número de casos de enfermos coincide con las condiciones de humedad ambiental y temperatura optimas para el desarrollo de las larvas de tercer estadio en los caracoles.Palabras clave: Angiostrongylus cantonensis, meningoencefalitis eosinofílica, humedad, temperatura, lluvia caída, correlación. ABSTRACTIntroduction: Angiostrongylus cantonensis is a helmint that lives in the pulmonary arteries of two rat’s species: Rattus rattus and Rattus norvergicus. Human is an accidental host that is infected by ingestion of third larvae stage in bad washed vegetables, fruit and different species of mollusks which constitute the intermitted hosts. Objective: To characterize the humidity, temperature and rain fall in zones where were reported the patients and its relation with the eosinophilic meningoencephalitis cases by Angiostrongylus cantonensis. Material and methods: 34 patients were diagnosed   with this illness. They were admitted at Hospital Pediatric San Miguel del Padrón, Havana, Cuba from January 1991until January 2014. In order to obtain of meteorological variables data we remit to the admission patient date and dairy and monthly register of the Meteorology Institute. Were calculated the correlation coefficient for each meteorological variable and the number of cases related to the different variables and the regression lines were performed. Results: The more quaintly of patients were grouped in periods where annual average fluctuated between 75 y 76 % and environment humidity oscillated between 65 y 80 %.The probability to find  illness cases is major in the years with average  annual rain between 68 and more of 120mm. An inverse correlation was observed for temperature. Conclusions: The larger number of reported cases coincides with the best conditions of environmental humidity and temperature for the development of the third stage larvae in mollusks.Key words: Angiostrongylus cantonensis, eosinophilic meningoencephalitis, humidity, temperature, rain fall, correlation.</p

Morbilidad en pacientes ingresados con sospecha de influenza a H1N1 en el Hospital Miguel Enríquez

Introducción: La aparición de la gripe pandémica A H1N1 afectó a varios países con una alta morbilidad. En nuestro país, se reportó un número importante de casos. Objetivo: Caracterizar la morbilidad de los pacientes ingresados en la Unidad de Cuidados Respiratorios del Hospital Miguel Enríquez, con síntomas compatibles de la enfermedad tipo Influenza A H1N1. Método: Se estudiaron 131 pacientes ingresados en el Hospital Dr. Miguel Enríquez en el período comprendido entre octubre del 2009 y agosto del 2010. Se evaluaron diferentes variables y se emplearon métodos estadísticos para determinar la relación entre ellas. Resultados: El rango de 40-49 años y el sexo femenino resultaron predominantes. El asma bronquial constituyó el factor de riesgo más frecuente, la neumonía, la complicación más encontrada y la tos, el síntoma cardinal. Conclusiones: Se comprueba clínicamente la presencia de Influenza A H1 N1 en los pacientes de la Unidad de Cuidados Respiratorios, con síntomas compatibles a esta entidad.Palabras clave: influenza A H1N1, asma bronquial, neumonía.</p