The Role of RIPK1/3 in Adult Onset Still’s Disease Patients With Liver Damage: A Preliminary Study

ObjectiveThis study aimed to investigate the distributions of lymphocytes in adult onset Still’s disease (AOSD) with liver dysfunction, and further prospectively explore whether receptor interacting serine/threonine kinases (RIPKs) in lymphocytes play a role in the pathogenesis of AOSD especially liver involvement.MethodsSeventy-two AOSD patients and 19 cases of healthy controls (HCs) were retrospectively reviewed, the AOSD group was then divided into liver damage (LD) group and non-liver damage (NLD) group, and the distributions of lymphocytes in peripheral blood were analyzed. Another independent 24 AOSD patients and 20 HCs were recruited for prospective study of RIPKs; the RIPKs in peripheral blood lymphocytes were detected by flow cytometry. Liver biopsy specimens were obtained from two AOSD patients and underwent immunochemistry analysis with RIPK1 and RIPK3 antibody.ResultsIn the retrospective study, AOSD showed significantly abnormal lymphocytes distributions, and disease activity was positively correlated with percentage of CD3+ T cells. LD patients were younger in age and showed higher disease activity score than NLD patients; they had higher frequencies of CD3+ T cells, especially higher CD8+ T cells (all p<0.05). In the prospective study, RIPKs in lymphocytes were significantly higher in AOSD patients than that of HCs, and LD patients also showed higher RIPKs expression than NLD patients. In addition, RIPKs were positively correlated with erythrocyte sedimentation rate (ESR) and disease activity in AOSD patients and LD and NLD subgroups (all p<0.05). Further, RIPKs expression was confirmed in two AOSD patients’ liver. ROC curve analysis indicated that RIPKs in lymphocytes (%) could be potential biomarkers in the diagnosis of AOSD and liver damage.ConclusionsAbnormal lymphocytes distributions and RIPKs expression were detected in AOSD. Aberrant expression of RIPKs in lymphocytes might be involved in the pathogenesis of AOSD. RIPKs could be candidate markers for AOSD and liver damage.

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The associations of circulating CD4+CD25highregulatory T cells and TGF-β with disease activity and clinical course in patients with adult-onset Still's disease

Connective Tissue Research ◽

10.3109/03008200903461462 ◽

2010 ◽

Vol 51 (5) ◽

pp. 370-377 ◽

Cited By ~ 17

Author(s):

Der-Yuan Chen ◽

Yi-Ming Chen ◽

Hsin-Hua Chen ◽

Chia-Wei Hsieh ◽

Chi‐Chen Lin ◽

...

Keyword(s):

T Cells ◽

Disease Activity ◽

Clinical Course ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Still's Disease ◽

Adult Onset Still's Disease

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

Rheumatology ◽

10.1093/rheumatology/keaa135 ◽

2020 ◽

Vol 59 (11) ◽

pp. 3293-3302 ◽

Cited By ~ 2

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 (> 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.

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Response to: ‘Changing the outcome measures, changing the results? The urgent need of a specific Disease Activity Score to adult-onset Still’s disease’ by Ruscitti et al

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218143 ◽

2020 ◽

pp. annrheumdis-2020-218143

Author(s):

Claudia Kedor ◽

Joachim Listing ◽

Jan Zernicke ◽

Eugen Feist

Keyword(s):

Disease Activity ◽

Outcome Measures ◽

Disease Activity Score ◽

Activity Score ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Specific Disease ◽

Still's Disease ◽

Adult Onset Still's Disease

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

The Journal of Rheumatology ◽

10.3899/jrheum.200617 ◽

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.

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