How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS).

How do autoimmune diseases cluster in families? A systematic review and meta-analysis

Background: A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods: Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results: Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions: Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity.

The multiple autoimmune syndromes. A clue for the autoimmune tautology

The multiple autoimmune syndromes (MAS) consist on the presence of three or more well-defined autoimmune diseases (ADs) in a single patient. The aim of this study was to analyze the clinical and genetic characteristics of a large series of patients with MAS. A cluster analysis and familial aggregation analysis of ADs was performed in 84 patients. A genome-wide microsatellite screen was performed in MAS families, and associated loci were investigated through the pedigree disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered. Three main clusters were established. Aggregation for type 1 diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with MAS were observed harboring autoimmunity genes. The MAS represent the best example of polyautoimmunity as well as the effect of a single genotype on diverse phenotypes. Its study provides important clues to elucidate the common mechanisms of ADs (i.e., autoimmune tautology). © Springer Science+Business Media, LLC 2012.

Carga viral de seis tipos de Virus del Papiloma Humano de alto riesgo y su asociacion con lesiones cervicales

Introducción: La infección por un tipo de Virus del Papiloma Humano de alto riesgo (VPH-AR), es el factor principal en el desarrollo de Cáncer de Cérvix (CC). La carga viral puede modular esta asociación, por lo que resulta importante su cuantificación y el establecimiento de su relación con lesiones precursoras de CC. Metodología: 60 mujeres con lesiones escamosas intraepiteliales (LEI) y 120 mujeres sin LEI, confirmadas por colposcopia, fueron incluidas en el estudio. Se determinó la carga viral de 6 tipos de VPH-AR, mediante PCR en tiempo real. Se estimaron OR crudos y ajustados para evaluar la asociación entre la carga viral de cada tipo y las lesiones cervicales. Resultados: 93.22% de mujeres con LEI y 91.23% de mujeres negativas, fueron positivas para al menos un tipo de VPH. VPH-18 y VPH-16 fueron los tipos más prevalentes, junto con VPH-31 en mujeres sin LEI. No se encontraron diferencias estadísticamente significativas de las cargas virales entre éstos dos grupos, aunque se observó un mayor carga viral en lesiones para algunos tipos virales. Una mayor frecuencia de lesiones se asoció a infecciones con carga baja de VPH-16 (ORa: 3.53; IC95%: 1.16 – 10.74), en comparación a mujeres con carga alta de VPH-16, (ORa: 2.63; IC95%: 1.09 – 6.36). En infecciones por VPH-31, la presencia de carga viral alta, se asoció con una menor frecuencia de lesiones (ORa: 0.34; IC95%: 0.15 – 0.78). Conclusiones: La prevalencia tipo-específica de VPH se corresponde con las reportadas a nivel mundial. La asociación entre la carga viral del VPH y la frecuencia de LEI es tipo específica y podría depender de la duración de la infección, altas cargas relacionadas con infecciones transitorias, y bajas cargas con persistentes. Este trabajo contribuye al entendimiento del efecto de la carga viral en la historia natural del CC; sin embargo, estudios prospectivos son necesarios para confirmar estos resultados.

Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1 ¨ ∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.