Both<i>HLA</i>class I and II regions identified as genome-wide significant susceptibility loci for adult-onset Still's disease in Chinese individuals

Li, Zhiqiang; Liu, Honglei; Chen, Jianhua; Zhang, Ting; Li, Meihang; Luo, Cainan; Liu, Shuang; Ding, Tingting; Yimaiti, Kuerbanjiang; Teng, Jialin; Li, Xingwang; Ding, Yonghe; Cheng, Xiaobing; Zhou, Juan; Ye, Junna; Ji, Jue; Su, Yutong; Shi, Hui; Sun, Yue; Gao, Chengwen; Hu, Qiongyi; Chi, Huihui; Yuan, Xuan; Zhou, Zhongzheng; Wang, Dong; Wang, Ke; Li, Changgui; Sun, Yuanchao; Niu, Yong; Chen, Linjie; Xu, Jian; Wu, Lijun; Zhou, Zhaowei; Pan, Dun; Niu, Haitao; Shi, Yongyong; Yang, Chengde

doi:10.1136/annrheumdis-2019-215239

Cited by 18 publications

(17 citation statements)

References 10 publications

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“…Of the seven identified proteins are, Agrin (AGRN), an extracellular matrix heparan sulfate proteoglycan (HSPG) with many distinct structural domains 70 , is detected in the cartilage of healthy patients, but its expression progressively decreases in chondrocytes of OA patients 71 , though it is upregulated in the synovial fluid of both OA and RA patients. Aldo–keto reductases (AKR1C2) are responsible for the conversion of prostaglandin (PG) E2 to PGF2α, and play a pro-inflammatory role in OA and RA 72 , such as leukocyte recruitment and stimulation of fibrotic processes in synoviocytes 73 . Cystathionine β-synthase (CBS) is a key enzyme for hydrogen sulphide (H 2 S) production from L-cysteine, as are cystathionine gamma-lyase and 3-mercaptopyruvate sulfurtransferase 74 .…”

Section: Discussionmentioning

confidence: 99%

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease

Pidde

Nishiyama

Oliveira

et al. 2021

Sci Rep

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The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.

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Section: Discussionmentioning

confidence: 99%

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease

Pidde

Nishiyama

Oliveira

et al. 2021

Sci Rep

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“…Thus, using different methods at multiple levels is crucial to understand the landscape of AOSD. In a previous study, we first screened the susceptibility of genetic factors in AOSD using a genome-wide association study and revealed that the SNPs rs3115628 (HLA class I region) and rs9268832 (HLA class II region) were strongly associated with AOSD in the Chinese population (4). Moreover, we identified plasma microRNA profiles using microRNA sequencing in patients with AOSD (12).…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of AOSD is complicated and still undetermined. AOSD could be affected by genetic background; for example, human leukocyte antigen (HLA) region-related mutations are closely related to the disease (2,4). Moreover, a recent report declared that cytomegalovirus infections may be implicated as trigger factors for AOSD (5).…”

Section: Introductionmentioning

confidence: 99%

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

et al. 2020

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Adult-onset Still's disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the α-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (all p < 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1β (IL-1β), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1β level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.

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“…Most of the previous genetic studies on AOSD revealed association with variants on human leukocyte antigen (HLA) class I and II regions, such as HLA-BW35, HLA-DRB1 * 15 and HLA-DRB1 * 04 [19,20]. However, the association was inconsistent and controversial among the various studies of different populations [27,28]. In addition, the results of genetic studies did not link to the pathogenesis, and none of them have been associated with AOSD disease outcomes [14,28].…”

Section: Introductionmentioning

confidence: 99%

“…However, the association was inconsistent and controversial among the various studies of different populations [27,28]. In addition, the results of genetic studies did not link to the pathogenesis, and none of them have been associated with AOSD disease outcomes [14,28]. Here, we enrolled 106 patients and 888 population controls and applied GWAS discovery and subsequent replication analysis to investigate the genetic susceptibility of AOSD.…”

Section: Introductionmentioning

confidence: 99%

Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease

Chen

Hung

Chang

et al. 2020

Journal of Immunology Research

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Adult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5′-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P=1.20×10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n=82, median: 9.31 pg/mL), particularly in the cases with activity score≥6 (n=42, 10.94 pg/mL), compared to the healthy donors (n=68, 5.31 pg/mL) (P<0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P<0.0001) or AT genotype (11.61 pg/mL) (P=0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.

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BothHLAclass I and II regions identified as genome-wide significant susceptibility loci for adult-onset Still's disease in Chinese individuals

Cited by 18 publications

References 10 publications

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease

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