Raisa Bu-Coifiu-Fanego

C3c intrathecal synthesis evaluation in patients with multiple sclerosis

INTRODUCTION Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). OBJECTIVE To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction. METHOD Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates. RESULTS High values over 80% of intrathecal synthesis were obtained except in one of the patients. CONCLUSION Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

Intrathecal synthesis of IgE in children with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

BackgroundEosinophilic meningoencephalitis caused by the helminth Angiostrongylus cantonensis, is an emerging infectious disease in America. The objective of this paper was to determine if the intrathecal synthesis of immunoglobulin E is produced during the acute phase of the disease.MethodsThirteen patients, mean age 4.5 years were studied; a diagnostic lumbar puncture was performed and serum samples taken. Immunoglobulin E (IgE) in serum and in cerebrospinal fluid (CSF) was quantified by nephelometry. Control patients had other infections or other neurological diseases.ResultsThe mean cell count in the CSF was 500 × 10-6 cells/L and of these 23% were eosinophils. In blood the eosinophils were 13%. The chief symptoms of the patients were migraine, vomiting and fever and 50% presented some meningeal signs. IgE intrathecal synthesis analyzed by the corresponding quotient diagram (Reibergram) was observed in all patients. No intrathecal IgE synthesis was seen in control patients.ConclusionIntrathecal synthesis of IgE demonstrates the participation of this immunoglobulin in the destruction of the third stage larvae of the parasite in the CSF. The test should be considered in our environment as a tool to aid diagnosis.

CSF/serum quotient graphs for the evaluation of intrathecal C 4 synthesis

BackgroundCerebrospinal fluid (CSF)/serum quotient graphs have been used previously to determine local synthesis in brain of immunoglobulins and C3 complement component. The aim of this study was to use the same technique to construct quotient graphs, or Reibergrams, for the beta globulin C4 and to evaluate the method for assessing intrathecal synthesis in neurological disease.MethodsThe 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,ResultsThe formula and C4 Reibergram with the constants previously found for IgA, determined the intrathecal C4 synthesis in CSF. The intrathecal C4 fraction in CSF (C4 loc 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 C4 under variable conditions of blood-CSF barrier permeability.ConclusionThe C4 Reibergram 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.

Reibergrama para la evaluación de la síntesis intratecal de C3c

RESUMEN - I n t roduccion: El diagrama de las razones de Reiber o re i b e rgrama cobra cada dia mayores usospara la caracterizacion de la sintesis intratecal de proteinas. El re i b e rgrama fue definido para las clasesm a y o res de inmunoglobulinas pero luego ha sido utilizado para evaluar otras proteinas basado en la teoriade la difusion molecular/velocidad de flujo del liquido cefalorraquideo (LCR). Metodo: El C3c, productode la degradacion del factor del complemento C3 y con una masa molecular de 145 KDa, se acerca a lascaracteristicas moleculares de la IgG para las leyes de la difusion de Fick. Se asume las constantes de la IgGen la formula de Reiber para evaluar la sintesis intratecal de C3c asi como su correspondiente re i b e rg r a m a .Se estudiaron 27 pacientes y 27 controles a los que se les dosifico albumina y C3c en suero y LCR porinmunodifusion radial. Resultados: Con el re i b e rgrama propuesto para el C3c se evaluaron estos pacientes.Se comprueba la validez de este re i b e rgrama para distintas condiciones de barrera con o sin sintesis intratecalde C3c.

Comparison of Major Immunoglobulins Intrathecal Synthesis Patterns in Ecuadorian and Cuban Patients with Angiostrongyliasis

Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cubas and Ecuadors patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid samples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis.

Intrathecal Activation as a Typical Immune Response within the Central Nervous System in Angiostrongyliasis

Angiostrongylus cantonensis is a zoonotic pathogen that occasionally causes human angiostrongyliasis; its main clinical manifestation is eosinophilic meningitis. This report defines the concept of intrathecal activation of complement as evidence of intrathecal synthesis of major immunoglobulins during this disease. Details are presented of the activation of complement system components in cerebrospinal fluid, and their application to our understanding of this tropical disease, which is emerging in the Western hemisphere. Intrathecal synthesis of at least one of the major immunoglobulins and a wide spectrum of patterns may be observed. Although intrathecal synthesis of C3c is always present, C4 intrathecal synthesis does not occur in every patient. The diversity of intrathecal synthesis and activation of the different complement pathways enables their division into three variant groups (A, B, and C). Variant group A includes the classical and/or lectin pathway and involves two or more major immunoglobulins with C3 and C4 intrathecal synthesis. Variant group B involves C4 in cerebrospinal fluid that comes from blood in the intrathecal activation of the classical pathway. Variant group C includes the alternative pathway.

Reibergram of Intrathecal Synthesis of C4 in Patients with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis

Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinal fluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinal fluid of affected patients.

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

IntroductionEosinophilic meningitis, a potentially fatal disease caused by Angiostrongylus cantonensis, is considered an emerging infectious disease.Case presentationThree Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis 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.ConclusionsTo the best of our knowledge, this is the first report of mannose-binding lectin deficiency associated with Angiostrongylus cantonensis 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.

SEASONAL DISTRIBUTION AND EVOLVING FORMS OF MULTIPLE SCLEROSIS PATIENTS DIAGNOSED FROM APRIL 2004 TO NOVEMBER 2007

BACKGROUND Multiple sclerosis (MS) was first reported in Cuba in 1965. The most frequent appearance is observed in the first six months of the year. OBJECTIVE To determine the seasonal distribution and evolving forms of MS patients diagnosed with the disease between April 2004 and November 2007. METHOD Twenty-one patients with suspected MS and 42 outbreaks were studied. Patients were classified according to Lublin and Revingolds criteria for clinical forms and according to McDonald. RESULTS Most patients were classified in outbreak and remission and only two patients classified as primary-progressive multiple sclerosis. The higher number of outbreaks occurred in the first two quarters of the year. CONCLUSION It is recommended to study further weather variables that may be related to the emergence of these outbreaks in our environment.

Detection of intrathecal IgM, IgG and IgA in a Cuban West Nile virus confirmed case

Laboratorio Central de Liquido Cefalorraquideo (LABCEL).Facultad de Ciencias Medicas “Dr. Miguel Enriquez” Habana, Cuba.Received 18 September 2007, received in final form 6 June 2008. Accepted 11 June 2008.Dra. Maritza Pupo-Antunez – Novia del Mediodia Km 6 ½ - La Lisa, Habana, Cuba. E-mail: mpupo@ipk.sld.cu