Separation of Anti-Ia (I-Region Associated Antigens) from Anti-H-2 Antibodies in Complex Sera, by Absorption on Blood Platelets. Description of Three New Ia Specificities 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66030/1/j.1399-0039.1976.tb01035.x.pd

Autoimmune Disease Classification by Inverse Association with SNP Alleles

With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS), ankylosing spondylitis (AS), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), Crohn's disease (CD), and type 1 diabetes (T1D), as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

High prevalence of ADHD symptoms in unmedicated youths with post-H1N1 narcolepsy type 1

Objectives To characterize attention deficit-hyperactivity disorder (ADHD) symptoms in unmedicated post-H1N1 narcolepsy type 1 (NT1) youths, and explore associations between ADHD symptoms and the narcolepsy phenotype. Methods A total of 50 consecutively enrolled post-H1N1 NT1 youths (7–20 years, 62% females, 98% HLA-DQB1∗06:02-positive, 98% CSF hypocretin-1 deficient, 88% vaccinated) were assessed after two weeks off medication for ADHD (ADHD diagnosis pre/post-narcolepsy, parent-rated ADHD symptoms) and narcolepsy-phenotyped (semi-structured interview, Stanford Sleep Questionnaire, Epworth Sleepiness Scale, polysomnography (PSG), Multiple Sleep Latency Test (MSLT)). Results In sum, 26 (52%) and 15 (30%) of participants had ADHD symptoms above and below the clinical significant cut-off, respectively, while 9 (18%) had no ADHD symptoms. High values were found for ADHD total score (mean (SD), 17.9 (9.5)) and ADHD subscores (inattentive score, 11.0 (6.3); hyperactive/impulsivity score, 6.9 (4.7)). These were significantly higher than previously reported in a mainly medicated narcolepsy cohort (p < 0.0001). Age, gender and disease duration did not influence scores. Two participants (4%) had ADHD diagnosis prior to narcolepsy onset. ADHD symptoms were correlated with parent-rated, but not with patient rated ESS scores, objective sleepiness (mean sleep latency), sleep fragmentation (sleep stage shift index, awakening index), or CSF hypocretin-1 level. Conclusion Comorbid ADHD symptoms were more prevalent in unmedicated post-H1N1 NT1 youths than previously reported in mainly medicated pediatric narcolepsy cohorts. The high prevalence was not due to pre-existing ADHD and generally not correlated with core narcolepsy sleep/wake phenotype characteristics, indicating that the ADHD symptoms were not a direct consequence of disturbed sleep or daytime sleepiness