A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo

Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine

Features associated with cardiac abnormalities in systemic lupus erythematosus

Objectives. To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. Methods. Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. Results. For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) ! 30 mm Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42-5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06-157.18). Elevated PAP was associated with age (1.04; 1.01-1.07) and with DI (1.20; 1.01-1.42). Conclusion. Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use. Lupus (2011) 20, 1518-1525

Sex Differences in Quality of Life in Patients With Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. Methods. Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. Results. A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages 6445 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. Conclusion. In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner

Cancer prevention by aspirin in children with Constitutional Mismatch Repair Deficiency (CMMRD)

Constitutional MisMatch Repair Deficiency (CMMRD) is caused by homozygous or compound heterozygous germline variants in one of the mismatch repair (MMR) genes (MSH2, MSH6, PMS2, MLH1). This syndrome results in early onset colorectal cancer, leukemia and lymphoma, brain tumors and other malignancies. Children with CMMRD are at high risk of developing multiple cancers and cancer surveillance does not guarantee detection of cancer at a curable stage. The development of a preventive treatment strategy would be a major step forward. Long-term daily use of acetylsalicylic acid (ASA) has been shown to reduce cancer risk in individuals with Lynch syndrome (LS). LS is caused by heterozygous germline variants of MSH2, MSH6, PMS2 and MLH1 and characterized by an increased risk of developing colorectal and endometrial cancer at adult age. Here we discuss the potential use of ASA for cancer prevention in patients with CMMRD