Elevated Levels of G-CSF in Patients with Active Phase of Adult-onset Still’s Disease

2020 ◽  
pp. jrheum.200617
Author(s):  
Yudong Liu ◽  
Shulan Zhang ◽  
Changshe Xia ◽  
Jiali Chen ◽  
Chunhong Fan
Keyword(s):  
Disease Activity ◽  
Therapeutic Potential ◽  
Assessment System ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Still's Disease ◽  
Elevated Liver Enzymes ◽  
Csf Levels ◽  
Adult Onset Still's Disease

Objective Neutrophilia is a hallmark of adult-onset Still’s disease (AoSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AoSD. Methods Sera were collected from 70 patients with AoSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory parameters, or LDGs levels in patients with AoSD were analyzed by Spearman’s correlation test. Results Active AoSD patients presented significantly higher levels of G-CSF compared to inactive AoSD patients (p<0.001) and HCs (p<0.0001). The levels of G-CSF were significantly decreased after active AoSD patients achieved disease remission (p=0.0015). The levels of G-CSF were significantly correlated with CRP, ESR, ferritin and systemic score in AoSD (p<0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (p<0.0001), neutrophil-to-lymphocyte ratio (p<0.0001), percentages of LDGs in the PBMCs (p=0.0042) as well as absolute numbers of circulating LDGs (p=0.0180) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (p<0.05). Conclusion Our findings indicate that G-CSF is implicated in the pathogenesis of AoSD, and targeting G-CSF may have therapeutic potential for AoSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi-Ming Chen ◽  
Wei-Ting Hung ◽  
Wan-Chun Chang ◽  
Chia-Wei Hsieh ◽  
Wen-Hung Chung ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Colony Stimulating Factor ◽  
Still's Disease ◽  
A Genome ◽  
Csf Levels ◽  
Stimulating Factor ◽  
Adult Onset Still's Disease

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.

scholarly journals Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3293-3302 ◽  
Author(s):  
Zhihong Wang ◽  
Huihui Chi ◽  
Yue Sun ◽  
Jialin Teng ◽  
Tienan Feng ◽  
...  
Keyword(s):  
Disease Activity ◽  
Multivariate Logistic Regression Analysis ◽  
Soluble Form ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Potential Predictor ◽  
Still's Disease ◽  
Chronic Course ◽  
Adult Onset Still's Disease

Abstract Objectives Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still’s disease (AOSD). Methods Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis. Results AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1β and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (&gt; 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients. Conclusion Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD.

Elevated plasma galectin-3 levels and their correlation with disease activity in adult-onset Still’s disease

2020 ◽  
Vol 39 (6) ◽  
pp. 1945-1952 ◽  
Author(s):  
Po-Ku Chen ◽  
Joung-Liang Lan ◽  
Ju-Pi Li ◽  
Ching-Kun Chang ◽  
Shih-Hsin Chang ◽  
...  
Keyword(s):  
Disease Activity ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Elevated Plasma ◽  
Still's Disease ◽  
Galectin 3 ◽  
Adult Onset Still's Disease

scholarly journals An Unusual Case of Adult-Onset Still’s Disease with Hemophagocytic Syndrome, Necrotic Leukoencephalopathy and Disseminated Intravascular Coagulation

2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Rajaie Namas ◽  
Naveen Nannapaneni ◽  
Malini Venkatram ◽  
Gulcin Altinok ◽  
Miriam Levine ◽  
...  
Keyword(s):  
Hemophagocytic Syndrome ◽  
Adult Onset Still’S Disease ◽  
Normocytic Anemia ◽  
High Dose ◽  
African American Female ◽  
Adult Onset ◽  
Still’S Disease ◽  
Still's Disease ◽  
Elevated Liver Enzymes ◽  
Adult Onset Still's Disease

Case. A 34-year-old African-American female with a history of adult-onset Still’s disease presented to an outside hospital with oligoarthritis. She experienced a generalized tonic-clonic seizureen routevia ambulance, was intubated upon arrival, and transferred to the intensive care unit for treatment of suspected pneumonia and sepsis. She subsequently developed generalized cutaneous desquamation that progressed despite the cessation of antibiotics and other potential offending drugs which required transfer to our hospital’s burn unit. She was suspected to have reactive hemophagocytic syndrome based on her clinical presentation of fever, rash, polyarthritis, elevated liver enzymes, coagulopathy, splenomegaly, normocytic anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis visualized in bone marrow biopsy specimen. Magnetic resonance imaging demonstrated necrotic demyelination of the deep white matter and corona radiata. The patient developed multiorgan dysfunction and DIC without any other attributable etiology. Despite aggressive broad spectrum therapy and high dose of steroids she progressively deteriorated and eventually expired.Conclusion. Previous publications have highlighted the prevalence of necrotic leukoencephalopathy in children with familial hemophagocytic syndrome. Our patient demonstrated some uncommon features complicating her HLH including DIC and necrotic leukoencephalopathy, which are very rare entities in AOSD.

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