[The relation between the HLA-DRB1*1501 allele and the severity of multiple sclerosis in a sample of the Spanish population from the Balearic Islands: the influence exerted by sex]. / Relación entre el alelo HLA-DRB1*1501 y la gravedad de la esclerosis múltiple en una muestra de población española perteneciente a las Islas Baleares: influencia del sexo.

INTRODUCTION: There is some controversy about the possible relation between HLA-DR2 (DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602) and the severity of multiple sclerosis (MS), which could be due, at least in part, to methodological differences among the different studies dealing with this subject and/or to a lack of phenotypic homogeneity within the series of patients. AIMS: This study aims to contribute information about the possible relation between DR2 (more specifically the HLA-DRB1*1501 allele) and the severity of MS. PATIENTS AND METHODS: We conducted a study of 43 individuals with clinically defined MS, whose degree of severity was determined using Kurtzke's EDSS, and 107 controls from a similar ethnic origin. DETERMINATIONS: HLA typing by PCR-SSO and PCR-SSP, analysis of oligoclonal IgG bands in CSF by isoelectric focusing, and quantification of the intrathecal synthesis of IgG (IgG index, IgG ratio, Reiber's formula and Tourtellotte's formula). STATISTICS: Chi2 test, Mann-Whitney test and Kendall correlation coefficient. RESULTS: DRB1*1501 is associated with the presence of MS only in females and with lower severity of the disease only in males. These associations do not appear to depend on any kind of effect exerted by DRB1*1501 on the intrathecal synthesis of IgG that differs between the two sexes. CONCLUSIONS: The absence of a relation between DRB1*1501 and the severity of MS reported in many studies could be due to not stratifying the patients according to sex. Our findings emphasise how important it is in genetic studies of complex traits to reduce the phenotypic heterogeneity of patients as much as possible.

Relación entre el alelo HLA-DRB1*1501 y la gravedad de la esclerosis múltiple en una muestra de población española perteneciente a las Islas Baleares: influencia del sexo / The relation between the hla-drb1*1501allele and the severity of multiple sclerosis in a sample of the spanish population from the Balearic Islands: the influence exerted by sex

Introducción. Hay controversia en cuanto a la posible relación entre HLA-DR2 (DRB1*1501-DRB5*0101-DQA1*0102DQB1*0602) y la gravedad de la esclerosis múltiple (EM), lo que puede deberse, almenos en parte, a diferencias metodológicas entre los diferentes estudios que han abordado este tema y/o falta de homogeneidad fenotípica dentro de las series de pacientes. Objetivo. Aportar información acerca de la posible relación entre DR2 (concretamente el alelo HLA-DRB1*1501) y la gravedad de la EM. Pacientes y métodos. Hemos estudiado 43 individuos con EM clínicamente definida, cuya gravedad se ha establecido mediante la EDSS de Kurtzke, y 107 controles de origen étnico similar. Se realizaron las siguientes determinaciones: tipificación HLA mediante PCR-SSO y PCR-SSP, análisis de bandas oligoclonales de IgG en el LCR por isoelectroenfoque, y cuantificación de la síntesis intratecal de IgG (índice de IgG, ratio de IgG, fórmula de Reiber y fórmula de Tourtellotte). Se aplicaron las siguientes pruebas estadística: test 2, test de Mann-Whitney y coeficiente de correlación Kendall. Resultados. DRB1*1501se asocia a la presencia de EM sólo en mujeres, y a una menor gravedad de la enfermedad sólo en hombres. Estas asociaciones no parecen depender de algún efecto de DRB1*1501 sobre la síntesis intratecal de IgG que sea diferente en ambos sexos. Conclusiones. La ausencia de relación entre DRB1*1501 y la gravedad de la EM descrita en muchos estudios podría obedecer a la falta de estratificación de los pacientes por sexo. Nuestros resultados resaltan la importancia que tiene para los estudios genéticos de rasgos complejos reducir lo máximo posible la heterogeneidad fenotípica de los pacientes (AU)

Introduction. There is some controversy about the possible relation between HLA-DR2 (DRB1*1501-DRB5*0101- DQA1*0102-DQB1*0602) and the severity of multiple sclerosis (MS), which could be due, at least in part, to methodological differences among the different studies dealing with this subject and/or to a lack of phenotypic homogeneity within the series of patients. Aims. This study aims to contribute information about the possible relation between DR2 (more specifically the HLA-DRB1*1501 allele) and the severity of MS. Patients and methods. We conducted a study of 43 individuals with clinically defined MS, whose degree of severity was determined using Kurtzke’s EDSS, and 107 controls from a similar ethnic origin. Determinations: HLA typing by PCR-SSO and PCR-SSP, analysis of oligoclonal IgG bands in CSF by isoelectric focusing, and quantification of the intrathecal synthesis of IgG (IgG index, IgG ratio, Reiber’s formula and Tourtellotte’s formula). Statistics: c 2 test, Mann-Whitney test and Kendall correlation coefficient. Results. DRB1*1501 is associated with the presence of MS only in females and with lower severity of the disease only in males. These associations do not appear to depend on any kind of effect exerted by DRB1*1501 on the intrathecal synthesis of IgG that differs between the two sexes. Conclusions. The absence of a relation between DRB1*1501 and the severity of MS reported in many studies could be due to not stratifying the patients according to sex. Our findings emphasise how important it is in genetic studies of complex traits to reduce the phenotypic heterogeneity of patients as much as possible (AU)

Two Spanish sibs with familial amyloidotic polyneuropathy homozygous for the V30M-TTR gene.

Two Spanish sibs with familial amyloidotic polyneuropathy (FAP) homozygous for the V30M-TTR gene, were diagnosed by DNA and protein analyses. Their clinical picture was very similar to the Majorcan FAP heterozygous patients except for the sensorimotor syndrome which was more aggressive. Noteworthy were clinical differences between the sibs concerning autonomic involvement, cranial neuropathy and kidney disturbances. These differences can be due to genetic and/or environmental factors.

Citocinas / Cytokines

Los estudios realizados en la última década sobre citocinas han permitido un notable avance en el conocimiento de estos mediadores hormonales producidos por la práctica totalidad de las células del organismo. Estos mediadores de corta vida media actúan sobre sus células diana previa unión al correspondiente receptor, lo que comporta una serie de reacciones que son básicas en el control del metabolismo, crecimiento y diferenciación celular. Estas proteínas de bajo peso molecular no suelen hallarse en el suero, ya que generalmente actúan de forma autocrina o paracrina, si bien en ocasiones ejercen una acción endocrina. El hecho de que una gran proporción de genes que dictan la producción de citocinas hayan sido clonados nos ha permitido afirmar la enorme multiplicidad y disparidad de éstas, a la vez que confirmar el importante papel fisiológico que juegan en las reacciones inmunológicas y en procesos inflamatorios, cáncer, hemostasia o reparación tisular. Si bien con resultados dispares, se ha iniciado ya la utilización de citocinas y/o sus inhibidores como agentes terapéuticos en la práctica clínica. La profundización en el estudio de estos mediadores está en la base de la obtención de los fármacos del futuro. (AU)

[The use of FD-6 monoclonal antibody in diagnosing and detecting the carriers of familial amyloidotic polyneuropathy type I]. / Utilidad del anticuerpo monoclonal FD-6 para el diagnóstico y la detección de portadores en la polineuropatía amiloidótica familiar tipo I.

Familial amyloidotic polyneuropathy type I (FAF-I) is caused by a specific genetic mutation that gives rise to a transthyretin anomaly whose presence in serum constitutes the biochemical marker for this disease. We studied the serum of 7 patients and 16 asymptomatic members of their immediate families using ELISA with FD-6 monoclonal antibody to detect the transthyretin anomaly. Positive results were found for the 7 patients, including the 2 patients whose disease was apparently sporadic, and 12 carriers were detected among the family members. This technique makes sural nerve biopsy unnecessary for establishing a diagnosis in patients whose clinical signs are consistent with FAP-I. Asymptomatic carriers are also detected, facilitating appropriate genetic counseling.