Identificación y utilidad clínica de los anticuerpos antineuronales / Identification and clinical usefulness of anti-neuronal antibodies

Revisamos los anticuerpos neuronales descritos en las enfermedades del SNC con el fin de clarificar su valor diagnóstico. En este estudio los anticuerpos neuronales asociados con los síndromes resultantes de la disfunción neuronal del SNC se clasifican en 2 grupos en función de la localización del antígeno dentro de la neurona o en la membrana celular. El grupo I incluye los anticuerpos cuya diana son antígenos intracelulares y probablemente no son patogénicos. Estos incluyen anticuerpos onconeurales (Hu [ANNA1], Yo [PCA1], Ri [ANNA2], CV2 [CRMP5], amphiphysin, Ma2, Tr, SOX1) que son útiles para el diagnóstico de los síndromes neurológicos paraneoplásicos (SNP). Otros anticuerpos de este grupo, principalmente anticuerpos anti-descarboxilasa del ácido glutámico (GAD), identifican otros síndromes no paraneoplásicos como el síndrome de la persona rígida (SPS), la ataxia cerebelar y la encefalitis límbica (LE). Los anticuerpos del grupo II reconocen antígenos de la superficie neuronal. Los anticuerpos de este grupo se asocian con síndromes característicos del SNC, pero su detección no indica que el trastorno sea paraneoplásico. Los más frecuentes son los anticuerpos anti-receptor NMDA, seguidos de los anticuerpos contra la proteína LGl1 asociada al canal de potasio. Otros anticuerpos menos comunes incluyen aquellos contra los receptores de AMPA, GABAb, mGluR 1 y 5 y contra CASPR2. Se sugiere un papel patogénico de los anticuerpos debido a la respuesta de los síntomas a la terapia inmunológica y la correlación entre la titulación del anticuerpo y los resultados neurológicos (AU)

We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value. In this work, the neuronal antibodies associated with syndromes resulting from CNS neuronal dysfunction were classified into two groups according to the location of the antigen inside the neuron or in the cell membrane. Group I includes antibodies that target intracellular antigens and are probably not pathogenic. They include onconeural antibodies (Hu [ANNA1], Yo [PCA1], Ri [ANNA2], CV2 [CRMP5], amphiphysin, Ma2, Tr, SOX1), which are useful for the diagnosis of paraneoplastic neurological syndromes (PNS). Other antibodies of this group, mainly anti-glutamic acid decarboxylase (GAD) antibodies, identify non-paraneoplastic syndromes (PNS), such as stiff-person syndrome (SPS), cerebellar ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal surface antigens. Antibodies in this group are associated with characteristic CNS syndromes, but their detection does not indicate that the disorder is paraneoplastic. The most frequent are the anti-receptor NMDA antibodies, followed by the antibodies against the protein LGI1 associated with the potassium channel. Other less common antibodies include those against the receptors of AMPA, GABAb, mGluR 1 and 5, and against CASPR2. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy, and the correlation between antibody titers and neurological outcome (AU)

Large Evaluation of Anti-Cardiolipin and anti-Beta2Glycoprotein I Assays: Results from the AutoimmunityWorkshop of the Spanish Society of Immunology

Despite their clinical utility and the importance that laboratory testshave in APS diagnosis, probably the most important drawback of suchtests is the elevated intra- and inter-laboratory variation. The aim of thepresent work was to assess the multilaboratory performance of aCL (..) (AU)

A pesar de la indudable utilidad clínica y de la importancia de laspruebas de laboratorio en el diagnóstico del síndrome antifosfolípido(APS), probablemente el mayor defecto de dichas pruebas es su elevadavariabilidad intra- e inter-laboratorio. El objetivo del presente trabajo fueevaluar el comportamiento de los ensayos (..) (AU)

Effectiveness of different methods for anti-Sm antibody identification. A multicentre study.

Methods for the measurement of autoantibodies frequently provide controversial results. The objective of the present study was to evaluate the performance of Spanish Clinical Laboratories in the measurement of anti-Sm antibodies. A total of 23 laboratories participated, analysing 30 serum samples from patients with systemic lupus erythematosus and other autoimmune and non-autoimmune diseases. The laboratories used four extractable nuclear antigen screens, eight enzyme-linked immunosorbent assays (ELISAs) specific for anti-Sm, one line-blot, one dot-blot and one double immunodiffusion assay, from 15 different manufacturers. A total of 871 results were obtained. In general, very good sensitivity was obtained (95-100%), but specificity was moderate (52-86%) and must be improved. Most ELISAs and the line-blot were valid assays for anti-Sm detection and could serve as tests both for analysis and/or confirmation. The likelihood ratios indicated that both methods can be considered very useful or useful for the determination of anti-Sm antibodies. Nevertheless, the analytical quality of the methods for the measurement of anti-Sm antibodies could probably be improved by standardisation of the methods and the participation of laboratories in external quality control programs.

Antinuclear antibodies (ANA) screening by enzyme immunoassay with nuclear HEp-2 cell extract and recombinant antigens: analytical and clinical evaluation.

OBJECTIVES: Immunofluorescence assay (IFA) has been the standard method for antinuclear antibodies (ANA). To simplify and standardize the ANA test, generic ANA solid phase enzyme immunoassay has been promoted. The objective of the present work has been to study the relationship with IFA and the clinical usefulness of a generic EIA for ANA (COBAS Core HEp-2 ANA EIA, Roche Diagnostics). DESIGNS AND METHODS: We studied 74 healthy individuals, 119 patients with defined systemic autoimmune diseases, 26 patients with other autoimmune diseases, and 490 routine samples sent to laboratory for ANA analysis. RESULTS: Precision study showed intra-assay coefficient of variations (CVs) below 8% and inter-assay CVs below 10%. In relation to IFA, a 0.6 kappa index of agreement was obtained. COBAS-ANA concentrations increased according to IFA titer and greatest COBAS-ANA responses were obtained with pure or mixed homogeneous patterns and centromeric patterns. Analysis of COBAS-ANA response to particular antigenic specificities showed that SS-B, Scl-70 and U1sn-RNP specificities were saturating at high concentrations, whereas Jo-1, SS-A and nuclear and centromeric specificities exhibited lower responses. Elevated serum concentrations of IgG and IgM did not interfere COBAS-ANA, but high serum rheumatoid factor (RF) concentrations produced a decrease of ANA. For systemic lupus erythematosus (SLE) patients, the COBAS-ANA best efficiency was obtained with a cut-off of 0.9, with a sensitivity of 97% and a specificity of 88%, whereas the best IFA-ANA efficiency was obtained with a 1:80 dilution, giving a sensitivity of 90% and a specificity of 99%. There were no differences between areas under ROC curves for COBAS-ANA and IFA-ANA. For other systemic and nonsystemic autoimmune diseases sensitivity and specificity of COBAS-ANA were similar or higher than that of 1:160 IFA-ANA titer. CONCLUSION: Sensitivity and specificity of COBAS Core ANA-EIA for SLE and other systemic and nonsystemic autoimmune diseases, together with performance characteristics make it an adequate automated system for ANA screening.