Progress in spondylarthritis. Progress in studies of the genetics of ankylosing spondylitis

Brown, Matthew A.

doi:10.1186/ar2692

Cited by 22 publications

(17 citation statements)

References 52 publications

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“…Although its etiology and pathogenesis are not yet fully understood, the genetic predisposition, environmental factors, and bacterial antigens may contribute. HLA B27 and several other genes are believed to contribute to the pathogenesis (2,8,10). Due to the effects of HLA-B 27 on the immune system, the opinions center around the damage by host tissues, infl ammation development and activation of cytokines (2,11).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis

Küçük¹,

Uslu²,

Ugan³

et al. 2015

BLL

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OBJECTIVE: Ankylosing spondylitis (AS) is a progressive chronic infl ammatory disease mainly characterized by axial skeleton and sacroiliac joint involvement. We aimed to investigate the relation between neutrophil-tolymphocyte ratio (NLR) and disease severity of AS and to explore its availability in clinical practice. METHODS: A total of 102 AS patients and 60 individuals who were age-and gender-compatible with the control group were included into the study. Patients were divided into 2 groups according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Patients with BASDAI scores < 4 were considered to be having mild disease activity, whereas those with scores ≥ 4 were considered to be displaying severe disease activity. Hemogram test during the diagnosis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and other laboratory values of the control group were recorded. RESULTS: NLR was observed to be higher in AS patients compared to the controls (2.47 ± 1.33 and 1.72 ± 0.47; respectively; p<0.0001). NLR was observed to be signifi cantly higher in severe AS disease activity compared to the mild AS disease activity (2.72 ± 1.41, 2.20 ± 1.19; respectively; p = 0.001). NLR had statistical signifi cant differences between mild disease activity compared to the controls (2.20 ± 1.19 and 1.72 ± 0.47, respectively; p = 0.263). There was a positive correlation between NLR and BASDAI (r = 0.193, p = 0.041). The performance of NLR evaluating the disease severity by Roc analysis had sensitivity of 69%, specifi city of 54% (cut-off value 1.91), and AUC of 0.652 (95% Cl, 0.549-0.755) (p = 0.006). CONCLUSIONS: NLR may be a simple and inexpensive marker to indicate disease activity in patients with AS in daily clinical practice (Tab.

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Section: Discussionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis

Küçük¹,

Uslu²,

Ugan³

et al. 2015

BLL

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“…Ankylosing spondylitis (AS) is considered a chronic inflammatory disorder of the axial skeleton involving mainly the sacroiliac joint and lumbar spine (Khan, 1998;Brown, 2009). AS is a form of arthritis that primarily affects the spine, although other joints can also be involved.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor receptor-II nt587 polymorphism in Chinese Han patients with ankylosing spondylitis

Li¹,

Wang²,

Ma³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We aimed to explore the association between the onset of ankylosing spondylitis (AS) and nt587 polymorphisms of the tumor necrosis factor receptor II (TNFRII) gene in the Han population of Hunan Province, China. Correlation analysis was performed in a case-control study involving 100 AS cases and 100 healthy controls. The nt587 single nucleotide polymorphism of the TNFRII gene was examined by polymerase chain reaction-restriction fragment length polymorphism. The relationship between AS and the frequencies of genotypes and alleles in TNFRII nt587 were analyzed using the SPSS software. There were 43 cases with the TNFRII nt587 T/T genotype, 32 cases with the TNFRII nt587 T/G genotype, and 25 cases with the TNFRII nt587 G/G genotype. In the 100 healthy controls, 56 subjects had the TNFRII nt587 5191 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 5190-5198 (2014) Relationship between TNFRII polymorphisms and AS T/T genotype, 34 had the TNFRII nt587 T/G genotype, and 10 had the TNFRII nt587 G/G genotype. The G allele frequency of the AS group was significantly higher (χ 2 = 8.734, P = 0.003) than that in the control group (41.0 vs 27.0%). The odds ratio (OR) in AS cases with the TNFRII nt587 G/G genotype was 3.256, which was obviously higher than in those with T/G (OR = 1.226) and T/T (OR = 1.0) genotype. The polymorphism at position nt587 of the TNFRII gene was found to be associated with AS, and the TNFRII nt587 G allele may play an important role in AS susceptibility. The TNFRII nt587 G/G genotype may increase the risk of developing AS in the Hunan population.

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“…Recent genome-wide association studies (GWAS) have revealed numerous ERAP1 polymorphisms to be associated with ankylosing spondylitis (AS)-a chronic inflammatory disease (15,16) strongly associated with the HLA-B27 MHC I allele. Interestingly, recent GWAS and replication studies (17) reveal a clear association of the rs30187 SNP in ERAP1, encoding a K 528 R variant, with reduced AS risk, and, importantly, demonstrate a haplotype of this SNP exclusively in the context of HLA B27.…”

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confidence: 99%

Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming

Kochan

Krojer

Harvey

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

232

286

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Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-ðXÞ 18 -E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K 528 R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.antigen presentation | ERAP1 mechanism | MHC restriction

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Progress in spondylarthritis. Progress in studies of the genetics of ankylosing spondylitis

Cited by 22 publications

References 52 publications

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis

Tumor necrosis factor receptor-II nt587 polymorphism in Chinese Han patients with ankylosing spondylitis

Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming

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