High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2.

Narcolepsy is a sleep disorder caused by an apparent degeneration of orexin/hypocretin neurons in the lateral hypothalamic area and a subsequent decrease in orexin/hypocretin levels in the cerebrospinal fluid. Narcolepsy is classified into type 1 (NT1) and type 2 (NT2). While genetic associations in the human leukocyte antigen (HLA) region and candidate autoantibodies have been investigated in NT1 to imply an autoimmune origin, less is known about the pathogenesis in NT2. Twenty-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-DRB3, -DRB4, -DRB5, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01 (odds ratio [OR]: 9.15; p = 8.31 × 10-4) and HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB4*01:03:01, -DRB1*04:01:01, -DQA1*03:02//03:03:01, -DQB1*03:01:01 (OR: 23.61; p = 1.58 × 10-4) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (n = 5) that was associated with the extended HLA-DQB1*06:02:01 haplotype (p = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (p = .8524). We confirmed the previous association of NT1 with HLA-DQB1*06:02:01 extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with HLA-DQB1*06:02:01 was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.

Home capillary sampling and screening for type 1 diabetes, celiac disease, and autoimmune thyroid disease in a Swedish general pediatric population: the TRIAD study.

Objective: To screen a general pediatric population for type 1 diabetes (T1D), celiac disease (CD), and autoimmune thyroid disease (AITD) after home capillary sampling. Methods: Swedish schoolchildren between 6-9 years and 13-16 years of age were invited to screening by taking a capillary sample at home. Samples were returned by mail and assessed for autoantibodies associated with T1D, CD, and AITD. Persistently autoantibody-positive children were referred for clinical follow-up. Results: Of 19,593 invited, 3,527 (18.0%) consented to participate and 2,315/3,527 (65.6%) returned a blood sample of sufficient volume. Hemolysis occurred in 830/2,301 (36.1%) samples. After exclusion of 42 children with previously known T1D, CD, or AITD, and two autoantibody-positive children who declined a confirmatory sample, 2,271/19,593 (11.6%) were included. 211/2,271 (9.3%) had persistent autoantibodies: 60/2,271 (2.6%) with T1D autoantibodies, 61/2,271 (2.7%) with CD autoantibodies, and 99/2,271 (4.4%) with AITD autoantibodies; 9/2,271 (0.4%) were autoantibody positive for ≥1 disease. After clinical follow-up, 3/2,271 (0.1%) were diagnosed with T1D, 26/2,271 (1.1%) with CD, and 6/2,271 (0.3%) with AITD. Children with a first-degree relative (FDR) with T1D, CD, and/or AITD, had higher occurrence of autoantibodies compared to children without an FDR (63/344, 18.3%, vs. 148/1,810, 8.2%) (p < 0.0001, OR 2.52, 95% CI 1.83-3.47), and higher occurrence of screening-detected diagnosis (14/344, 4.1%, vs. 21/1,810, 1.2%) (p < 0.0001, OR 3.61, 95% CI 1.82-7.18). Half of these children screened positive for another disease than the FDR. Conclusion: Screening for T1D, CD, and AITD by home capillary sampling in a Swedish general pediatric population detected autoimmunity in 9.3% and undiagnosed disease in 1.5%.

Prevalence of viral markers among first-time Arab blood donors in Kuwait.

BACKGROUND: The aim of this study was to assess the effect of blood donation modes on the prevalence of viral markers among Arab first-time blood donors in Kuwait. STUDY DESIGN AND METHODS: Donor ethnic background was classified as Kuwaiti nationals and non-Kuwaiti Arabs. A total of 26,874 donors were screened in 2002 for the following viral markers: hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc), human immunodeficiency virus-1 and -2 antibody (anti-HIV-1 and -2), HIV p24, and human T lymphotropic virus-I and -II antibody (anti-HTLVI/II). All samples positive for the presence of anti-HBc were tested for anti-HBs. Among these donors, 12,798 were first-time donors of which 74 percent were replacement and 26 percent were volunteers. RESULTS: The prevalence of HCV among replacement donors was significantly higher than the volunteer group. The difference between the two modes of blood donations, however, was not significant for HBsAg. The prevalence of anti-HCV among Kuwaiti national and non-Kuwaiti Arab first-time donors was 0.8 and 5.4 percent, respectively, whereas the prevalence of HBsAg was 1.1 and 3.5 percent, respectively, with the difference being significant at a p level of <0.0001. The difference observed for prevalence of anti-HBc among Kuwaiti national and non-Kuwaiti Arab donors (17 and 33.3%, respectively) was significant (p < 0.0001). Among first-time donors, 13.7 percent were positive for the presence of anti-HBs, indicating that 13.7 percent of the total Arab donor population might have had a previous infection and possible immunity to hepatitis B virus (HBV). CONCLUSION: A high prevalence of HBV and HCV was found among non-Kuwaiti Arab donors. The prevalence of anti-HCV was only significantly higher among replacement versus volunteer first-time donors. Therefore, there is a need to develop a strategic plan that incorporates the diverse background of the blood donors living in Kuwait.

Perceptions of adolescents involved in promoting lower-fat foods in schools: associations with level of involvement.

This article describes perceptions of adolescents involved in peer-led school-based nutrition promotions encouraging lower-fat food purchases and assesses the differences by level of student involvement. Surveys were administered at schools. Data were collected from 397 high school students from 10 Minnesota schools randomized to the intervention condition of the Trying Alternative Cafeteria Options in Schools study. Students were categorized as highly involved (n=54) or less involved (n=343) based on their level of involvement in promotional activity implementation. Chi 2 tests were conducted to measure the differences between highly-involved and less-involved students in perceptions and attitudes about lower-fat foods. Highly-involved students were significantly more likely than less-involved students to report more healthful eating behaviors and positive attitudes toward lower-fat foods. Student involvement in nutrition interventions should be integrated into programs aimed at increasing healthful food choices among adolescents.