Epstein–Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti‐DNA

Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities – anti‐dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two‐thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two‐thirds of SLE patients reacted to a large spectrum of self‐molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein–Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.     

Admission Norton scale scores (ANSS) correlate with rehabilitation outcome and length in elderly patients with deconditioning

We sought to determine if admission Norton scale scores (ANSS) used for evaluating pressure ulcer risk also correlate with rehabilitation outcome and length in elderly patients with deconditioning. This was a retrospective study conducted in a geriatric department between June 2008 and June 2010. The medical charts of consecutive elderly (≥65 years) patients admitted for rehabilitation due to deconditioning were studied for the following measurements: ANSS, admission albumin serum levels, mini-mental status examination (MMSE) scores, discharge walking functional independence measure (FIM) scores, discharge transfer FIM scores, and rehabilitation length. The cohort included 152 patients: 79 (52%) females and 73 (48%) males. Mean age was 83.6±6.5 years. The three most common causes of deconditioning were pneumonia, congestive heart failure exacerbation, and falls. ANSS correlated with discharge walking FIM scores (r=0.32; p=0.003), discharge transfer FIM scores (r=0.30; p=0.005), and length of rehabilitation (r=-0.37; p<0.0001), following adjustment for age, albumin serum levels, and MMSE scores. Linear regression analysis showed that ANSS were independently associated with discharge walking FIM scores (p=0.004), discharge transfer FIM scores (p=0.006), and rehabilitation length (p<0.0001). We conclude that the Norton scoring system may be used for predicting the outcome and the length of rehabilitation in elderly patients with deconditioning.     

Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia

Aims Autosomal dominant hypercholesterolaemia (ADH) is a major risk factor for coronary artery disease. This disorder is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). However, in 41% of the cases, we cannot find mutations in these genes. In this study, new genetic approaches were used for the identification and validation of new variants that cause ADH. Methods and results Using exome sequencing, we unexpectedly identified a novel APOB mutation, p.R3059C, in a small-sized ADH family. Since this mutation was located outside the regularly screened APOB region, we extended our routine sequencing strategy and identified another novel APOB mutation (p.K3394N) in a second family. In vitro analyses show that both mutations attenuate binding to the LDLR significantly. Despite this, both mutations were not always associated with ADH in both families, which prompted us to validate causality through using a novel genetic approach. Conclusion This study shows that advances in genetics help increasing our understanding of the causes of ADH. We identified two novel functional APOB mutations located outside the routinely analysed APOB region, suggesting that screening for mutations causing ADH should encompass the entire APOB coding sequence involved in LDL binding to help identifying and treating patients at increased cardiovascular risk.