| 1. |
- Gyllenberg, A, et al.
(författare)
-
Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
-
Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
-
Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
|
|
| 2. |
- Sun, Chengjun, et al.
(författare)
-
CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
-
Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
|
|
| 3. |
- Singh, R. N., et al.
(författare)
-
Influence of hydrogen content on impact toughness of Zr-2.5Nb pressure tube alloy
- 2011
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 1872-759X .- 0029-5493. ; 241:7, s. 2425-2436
-
Tidskriftsartikel (refereegranskat)abstract
- Influence of hydrogen content on the impact toughness of Zr-2.5% Nb alloy was examined by carrying out instrumented drop weight tests in the temperature range of 25-250 degrees C using curved Charpy specimens fabricated from unirradiated pressure tubes of Indian Pressurized Heavy Water Reactor (IPHWR). Hydrogen content of the samples was between 10 and 170 ppm by weight (wppm). Sharp ductile-to-brittle-transition behaviour was demonstrated by hydrided materials. The temperature for the onset of transition increased with the increase in the hydrogen content of the specimens. The fracture surfaces of unhydrided specimen exhibited ductile fracture caused by micro void coalescence and tear ridges at lower temperatures and by fibrous fracture at intermediate and at higher temperatures. Except for the samples tested at the upper shelf energy levels, the fracture surfaces of all hydrided samples were suggestive of hydride assisted failure. In most cases the transverse cracks observed in the fracture path matched well with the hydride precipitate distribution and orientation. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 4. |
- Ståhle, Magnus U., et al.
(författare)
-
Pathogen Inactivation of Human Serum Facilitates its Clinical Use for Islet Cell Culture and Subsequent Transplantation
- 2011
-
Ingår i: Cell Transplantation. - 0963-6897 .- 1555-3892. ; 20:5, s. 775-781
-
Tidskriftsartikel (refereegranskat)abstract
- Serum is regarded as an essential supplement to promote survival and growth of cells during culture. However, the potential risk of transmitting diseases disqualifies the use of serum for clinical cell therapy in most countries. Hence, most clinical cell therapy programs have replaced human serum with human serum albumin, which can result in inferior quality of released cell products. Photochemical treatment of different blood products utilizing Intercept (R) technology has been shown to inactivate a broad variety of pathogens of RNA and DNA origin. The present study assesses the feasibility of using pathogen-inactivated, blood group-compatible serum for use in human pancreatic islet culture. Isolated human islets were cultured at 37 degrees C for 3-4 days in CMRL 1066 supplemented with 10% of either pathogen-inactivated or nontreated human serum. Islet quality assessment included glucose-stimulated insulin release (perifusion), ADP/ATP ratio, cytokine expression, and posttransplant function in diabetic nude mice. No differences were found between islets cultured in pathogen-inactivated or control serum regarding stimulated insulin release, intracellular insulin content, and ADP/ATP ratio. Whether media was supplemented with treated or nontreated serum, islet expression of IL-6, IL-8, MCP-1, or tissue factor was not affected. The final diabetes-reversal rate of mice receiving islets cultured in pathogen-inactivated or nontreated serum was 78% and 87%, respectively (NS). As reported here, pathogen-inactivated human serum does not affect viability or functional integrity of cultured human islets. The implementation of this technology for RNA- and DNA-based pathogen inactivation should enable reintroduction of human serum for clinical cell therapy.
|
|
