HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms

Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex genes primarily involved are most often those encoding the peptide-presenting HLA class I or II molecules. A probable mechanism is preferential presentation by the disease-associated HLA molecules of peptides from autoantigens to T cells. Recent studies have shown, however, that other genes in the HLA complex also contribute. Taken together, available evidence suggests that the HLA complex harbour both disease predisposing genes which are quite specific for some autoimmune diseases (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for several diseases. This will be briefly reviewed in the following.     

Several genes in the extended human MHC contribute to predisposition to autoimmune diseases

Autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, affect approximately 4% of the population in industrialized countries, and are characterized by an immune-mediated destruction of autologous cells and/or tissues. More knowledge is needed to prevent and treat this large group of diseases. Unravelling the genetic predisposing factors is important in this respect, and large research efforts have been initiated to reach this goal. The human MHC, also called the human leukocyte antigen (HLA) complex, is known to harbour major genetic determinants for autoimmune diseases. For several autoimmune diseases certain classical HLA class II and/or class I genes are strongly associated with disease. As a result of recent systematic screening studies additional genes and regions in the MHC, including the extended MHC, are now known to contribute to the predisposition.     

Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients

Chromosome region 2q33 encodes several regulators of the immune system, among these the CD28, CTLA4, and ICOS molecules. Involvement of these genes in multiple sclerosis (MS) is not yet clear. We investigated six microsatellites and three SNPs in a relatively large and clinically well characterised Norwegian MS cohort. No associations were observed for any of the markers analysed in 575 MS patients and 551 controls. Associations were neither found when stratifying the material for the HLA-DRB1*1501, DQB1*0602 haplotype, gender, age at onset, disease course nor familial aggregation. In conclusion, this study could not confirm association with the CD28/CTLA4/ICOS gene region.     

Quality of care in stroke prevention: results of an audit study among general practitioners

BACKGROUND: In identifying opportunities to improve the quality of stroke prevention in general practice, insight in areas of suboptimal care is essential. This study investigated the quality of care in stroke prevention in general practice and its relation to the occurrence of stroke. METHODS: Retrospective case-based audit with guideline-based review criteria and final judgment of suboptimal care by an expert panel. RESULTS: A total of 292 stroke patients were identified through stroke registers of two main referral hospitals for stroke in Rotterdam. The general practitioners (GPs) (n = 95) of these patients were approached. The overall response rate from GPs was 81%, and a total of 193 patients from 77 GPs were included in the study. Data on the process of care at patient level were collected by chart review and by structured interviews with GPs during site visits. All cases were presented to a six-member panel of GPs and neurologists. In 44% of the cases, suboptimal care was identified (31% judged as possibly or likely failing to prevent stroke). Of the total number of identified shortcomings, 52% was related to inadequate hypertension control, particularly lack of follow-up after established hypertension. Another 17% of identified shortcomings concerned inadequate cardiovascular risk assessment. CONCLUSIONS: A substantial number of shortcomings in care, particularly in the domain of hypertension control and the assessment of patient's risk profiles for cardiovascular disease (CVD), were identified. This study suggests that improving preventive care delivery in general practice could reduce the occurrence of stroke.     

Tuberculous orchiepididymitis diagnosed by nucleic acid amplification test: A case report

Symptoms of tuberculous orchiepididymitis in a 39-year-old male started with swelling of left scrotum, followed by fistula formation with suppurative discharge. There was no any improvement produced by antibiotics. Surgical extirpation of inflammatory destroyed testicle and epidydimis was performed. Presence of tubercle bacilli was not shown by bacteriological analysis of testicle tissue. Tuberculous etiology was suggested after histopathological examination of testis and epididymis. Exudate from surgical wound was examined on presence of Mycobacterium tuberculosis DNA. Etiology of orchiepididymitis was proved by positive assay and inflammatory process was completely cured by antituberculotics therapy. By this report it was clearly shown that sometimes only molecular methods could confirm etiology of inflammatory process.     

Physical fitness and physical activity in obese and nonobese Flemish youth

OBJECTIVE: To assess different aspects of physical fitness and physical activity in obese and nonobese Flemish youth. RESEARCH METHODS AND PROCEDURES: A random sample of 3214 Flemish schoolchildren was selected and divided into an "obese" and "nonobese" group based on body mass index and sum of skinfolds. Physical fitness was assessed by the European physical fitness test battery. Physical activity was estimated by a modified version of the Baecke Questionnaire. RESULTS: Obese subjects had inferior performances on all tests requiring propulsion or lifting of the body mass (standing-broad jump, sit-ups, bent-arm hang, speed shuttle run, and endurance shuttle run) compared with their nonobese counterparts (p < 0.001). In contrast, the obese subjects showed greater strength on handgrip (p < 0.001). Both groups had similar levels of leisure-time physical activity; however, nonobese boys had a higher sport index than their obese counterparts (p < 0.05). DISCUSSION: Results of this study show that obese subjects had poorer performances on weight-bearing tasks, but did not have lower scores on all fitness components. To encourage adherence to physical activity in obese youth, it is important that activities are tailored to their capabilities. Results suggest that weight-bearing activities should be limited at the start of an intervention with obese participants and alternative activities that rely more on static strength used.