Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin Disease

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR = 0.49, p = 0.003). A strong protective association was found for higher ratios activating/inhibitory KIR (OR = 0.44, p = 0.001). KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR = 0.34, p<10−3) suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T) was decreased in patients. There is evidence that HLA-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR = 0.07, p = 0.001) stronger than KIR3DS1-Bw4(80I) (OR = 0.31, p = 0.002). Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

The A/A genotype is associated to increased susceptibility to pemphigus foliaceus.

<p>In parentheses, the total number of individuals in the sample. B/x indicates A/B or B/B genotypes. Euro: predominantly European background; Afro: mixed subsample, with predominantly African background; Total: total sample.</p

Frequency of the number of activating and inhibitory <i>KIR</i> genes in patients and controls.

<p>Only the Euro population was considered. (<b>A</b>) <i>KIR2DL4</i> was counted as activating gene and the deleted <i>KIR2DS4</i> was not counted as activating or inhibitory. Significant negative association was found for the presence of more than 3 activating genes (OR  = 0.49; 95% CI = 0.30–0.79; p = 0.003). (<b>B</b>) <i>KIR3DL3</i> was not included as inhibitory. (<b>C</b>) Significant negative association was found for the ratio higher than 0.75 (OR  = 0.44; 95% CI  = 0.27–0.73; p = 0.001).</p

Summary of <i>KIR</i> association studies regarding autoimmune diseases.

<p>Summary of <i>KIR</i> association studies regarding autoimmune diseases.</p

Genetic association between pemphigus foliaceus and five <i>KIR</i> genes.

<p>In parentheses, the total number of individuals in the sample. Only genes which presented significant (P<0.05) association in at least one population sample are shown. The frequencies of all <i>KIR</i> genes are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039991#pone.0039991.s001" target="_blank">Table S1</a>.</p><p>Euro: predominantly European background; Afro: mixed subsample, with predominantly African background.</p>*<p>For the total sample (combining the Euro and Afro populations) we found a significant association for <i>KIR3DL1</i>: OR  = 2.1, 95% CI 1.05–4.14, p = 0.033.</p

Association analyzes for the combinations KIR x HLA ligands.

<p>The bars indicate the 95% confidence interval and the black spot indicates the OR. The results for the Euro sample are shown. The results for the two population strata and the complete information about <i>KIR</i> and <i>HLA</i> combinations are found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039991#pone.0039991.s002" target="_blank">Table S2</a>. *at least one Bw4 epitope (80I from <i>HLA-A</i> or <i>HLA-B</i> loci or 80T).</p

Association analyzes between pemphigus foliaceus and HLA ligands of KIR.

<p>In parentheses, the total number of individual in the sample. Euro: predominantly European background; Afro: mixed subsample, with predominantly African background; Total: total sample. *at least one Bw4 epitope (80I from <i>HLA-A</i> or <i>HLA-B</i> loci or 80T).</p

Long Non-Coding RNAs in Multifactorial Diseases: Another Layer of Complexity

Multifactorial diseases such as cancer, cardiovascular conditions and neurological, immunological and metabolic disorders are a group of diseases caused by the combination of genetic and environmental factors. High-throughput RNA sequencing (RNA-seq) technologies have revealed that less than 2% of the genome corresponds to protein-coding genes, although most of the human genome is transcribed. The other transcripts include a large variety of non-coding RNAs (ncRNAs), and the continuous generation of RNA-seq data shows that ncRNAs are strongly deregulated and may be important players in pathological processes. A specific class of ncRNAs, the long non-coding RNAs (lncRNAs), has been intensively studied in human diseases. For clinical purposes, lncRNAs may have advantages mainly because of their specificity and differential expression patterns, as well as their ideal qualities for diagnosis and therapeutics. Multifactorial diseases are the major cause of death worldwide and many aspects of their development are not fully understood. Recent data about lncRNAs has improved our knowledge and helped risk assessment and prognosis of these pathologies. This review summarizes the involvement of some lncRNAs in the most common multifactorial diseases, with a focus on those with published functional data