Gammapatías biclonales: estudio retrospectivo de 47 pacientes / Biclonal gammopathies: retrospective study of 47 patients

Objetivo. Las gammapatías biclonales se caracterizan por una proliferación clonal de cálulas plasmáticas, o sus progenitores linfoides B, con producción de dos inmunoglobulinas anormales (proteínas M o paraproteínas). No conocemos estudios que hayan analizado esta patología en España. Hemos estudiado las enfermedades subyacentes, características de las paraproteínas y evolución de una serie de pacientes con gammapatía biclonal. Material y métodos. Se revisaron las gammapatías clonales del Servicio de Inmunología del Hospital Puerta de Hierro de Madrid, entre los años 1970 y 2011, seleccionando aquellos pacientes con gammapatía biclonal en una determinación. Se recogieron datos epidemiológicos, enfermedad de base, patologías asociadas, terapias recibidas, paraproteína y cuantificación de inmunoglobulinas. Resultados. De los 1.626 casos de gammapatías clonales, 47 eran gammapatía biclonal (2,89%). La mediana de seguimiento fue de 2 años. La principal entidad asociada fue la gammapatía biclonal de significado indeterminado. La composición de paraproteínas más frecuente fue IgG-IgG. En el 81% de los pacientes con una segunda determinación de paraproteína, había desaparecido al menos un componente M. Un tercio de los pacientes no había recibido tratamiento. Conclusiones. Las gammapatías biclonales se asocian fundamentalmente a gammapatía biclonal de significado indeterminado. Ninguna gammapatía biclonal de significado indeterminado evolucionó a patología maligna. En un elevado porcentaje desapareció al menos uno de los dos componentes clonales, a veces de forma espontánea (AU)

Objectives. Biclonal gammopathies are characterized by the clonal proliferation of plasma cells or their B-lymphoid progenitors and are associated with the production of abnormal immunoglobulins (M proteins or paraproteins). There are no known studies that have analyzed this disease in Spain. We studied the underlying diseases, characteristics of paraproteins and the evolution of a series of patients with biclonal gammopathy. Material and methods. We reviewed clonal gammopathies at the Department of Immunology of Hospital Puerta de Hierro in Madrid, between 1970 and 2011, selecting those patients with biclonal gammopathy in one reading. We collected data on the patient's epidemiology, underlying disease, associated diseases, therapies and paraprotein and immunoglobulin levels. Results. Of the 1626 cases of clonal gammapathies, 47 were biclonal gammopathy (2.89%). The median follow-up was 2 years. The main associated condition was biclonal gammopathies of undetermined significance (BGUS). The most common paraprotein combination was IgG-IgG. Upon conducting a second paraprotein reading, 81% of the patients had lost at least 1 monoclonal component. A third of the patients had not undergone treatment. Conclusions. Biclonal gammopathy are fundamentally associated with biclonal gammopathies of undetermined significance. No biclonal gammopathies of undetermined significance evolved to a malignant disease. In a high percentage of patients, at least 1 of the 2 clonal components disappeared, sometimes spontaneously (AU)

Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion.

The process of allelic exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of allelic exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoallelic recruitment during establishment of allelic exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before allelic exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH allelic exclusion, monoallelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.