Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the ...objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module.
In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49–56year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance.
•Transcriptional senescence starts earlier than proposed.•49–56year old age range is proposed as a critical point.•Immunosenescence genes are involved in cancer, immune regulation, cellular growth and maintenance.•Aging of the transcriptome in PBMC is a longitudinal process.•Not only young vs old, but a continuous sample must be studied in aging studies.
Background: The association between multiple sclerosis (MS) and the HLA-DRB1*15:01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene ...variants and sex have been proposed to modulate this association.
Objectives: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression.
Methods: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP.
Results: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107–1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 (p < 0.001), DRB5 (p < 0.001) and DQA1 (p = 0.004) in patients. DRB1 (p = 0.004) and DRB5 (p < 0.001) were also overexpressed in *15:01 controls.
Conclusions: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.
Being a woman increases the risk of developing multiple sclerosis, an illness where biopsychosocial factors (psychological stress, perceived social support, psychological well-being, coping ...strategies) may have a clinical impact.
To assess how stress management is affected in remitting-relapsing multiple sclerosis and to analyze gender differences both in terms of stress management and patients' cognitive performance.
42 patients were neuropsychologically evaluated with the Brief Repeatable Battery of Neuropsychological Tests, four psychosocial questionnaires and Beck's Depression Inventory. Two main analyses were conducted: mean comparisons between men and women for clinical, neuropsychological and psychosocial variables, and a correlation analysis between the psychosocial and clinical variables of the illness in the whole sample, as well as in men and women separately.
Men and women showed differences in the outbreak rate and in the attention/executive function domain. The correlation analysis revealed that the strongest correlation was between clinical and psychosocial variables when the group was divided according to gender. Any predominant coping strategy was not detected in the multiple sclerosis group, but it was observed that women had an increased tendency to self-incriminate.
This study emphasizes the importance of assessing these remitting-relapsing multiple sclerosis patients both cognitively and psychosocially, differentiating them by gender.
We report the first documented case of retrobulbar optic neuropathy associated with golimumab. A 48-year-old man was admitted with a 3-week history of progressive visual loss of his left eye. He had ...received a second infusion of golimumab for ankylosing spondylitis 10 days before admission. A magnetic resonance imaging scan showed enhancement of both optic nerves and visual evoked potentials were consistent with demyelinating bilateral optic neuropathy, although visual acuity drop in the right eye could not be determined because of deep amblyopia. No improvement was observed after golimumab dechallenge or corticosteroid treatment. Demyelinating complications related to treatment with tumor necrosis factor alpha inhibitors (TNFAI) have been previously described. Golimumab, a fully human monoclonal antibody, is the most recently developed TNFAI and thus, fewer adverse effects have been reported. Further studies should be developed to elucidate if variability in golimumab's pharmacokinetics or TNF receptor binding affinity could explain different safety profiles compared with other TNFAI.
