Clinical outcome and laboratory markers for predicting disease activity in patients with disseminated opportunistic infections associated with anti-interferon-γ autoantibodies

Background:In the acute phase of adult-onset Still’s disease (AOSD), elevated levels of proinflammatory cytokines including interferon-γ (IFN-γ) are shown. Moreover, IFN-γ impacts on activating macrophages which play a crucial role in the pathogenesis of AOSD. Natural killer (NK) cells and T helper cells are in charge of secreting IFN-γ in the innate and adaptive immune systems of disease, respectively. However, the features of their IFN-γ-producing variation depending on disease activity are still uncertain in AOSD.Objectives:We investigated characteristics of IFN-γ-producing CD4+T cells and NK cells in patients with AOSD.Methods:Twenty-four patients in the acute phase of AOSD (active AOSD), 8 of them after treatment (remission), and 12 healthy controls (HC) were recruited in this study. Peripheral blood mononuclear cells and serum samples were provided from them for the experimental analysis. Flow cytometry was used for analyzing CD4+T cells, CD4+regulatory T cells (Tregs), NK cells, and their intracellular IFN-γ expression levels as well as suppression assay of Tregs. The serum concentration of interleukin-18 (IL-18) was measured using commercially available ELISA kit. Relationship between the analyzed data and clinical findings related to disease activity were statistically evaluated.Results:IFN-γ expression in CD4+T cells was significantly higher in active AOSD than in HC (p < 0.05). Tregs also significantly indicated higher expression of IFN-γ in active AOSD than in HC (p < 0.0001); and moreover, Tregs were significantly impaired in their suppression ability (p < 0.05). In both CD4+T cells and Tregs, expression of IFN-γ was significantly correlated with serum ferritin levels in active AOSD (p < 0.05). IFN-γ expression in CD4+T cells was significantly higher in patients with splenomegaly than those without that (p < 0.05). The proportion of NK cells was significantly lower in active AOSD than in HC (p < 0.005), whereas IFN-γ expression in NK cells was significantly higher in active AOSD than in HC (p < 0.0005). The number of NK cells and IFN-γ-expressing NK cells had inverse relationship with serum ferritin levels in active AOSD (p < 0.05 and p < 0.005, respectively). Increased number of NK cells and their decreased expression of IFN-γ were significantly demonstrated in remission (p < 0.05). In the analyses of NK cell subsets, lower expression of IFN-γ in CD56brightNK cells and higher that in CD56dimNK cells were significantly indicated in active AOSD than HC (p < 0.05). In remission, IFN-γ expression was significantly decreased in CD56dimNK cells (p < 0.05) despite no significant recovery of that in CD56brightNK cells (p = 0.311). Meanwhile, increased expression of IFN-γ in CD56brightNK cells was demonstrated in only patients who were treated with biologics. Although serum levels of IL-18 were significantly higher in active AOSD than in remission and HC; however, they had no significant correlations with any analyzed data.Conclusion:CD4+T cells and NK cells promote IFN-γ expression in the acute phase of AOSD. Meanwhile, increased expression of IFN-γ in CD4+T cells and decreased number of NK cells were correlated with serum ferritin levels, suggesting that they are indicators of disease activity. Furthermore, high disease activity may impact on the alteration of IFN-γ-producing balance in two distinct population of NK cells, and the plasticity of Tregs leading to defect in suppression ability.Disclosure of Interests:None declared

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The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia

PLoS ONE ◽

10.1371/journal.pone.0135042 ◽

2015 ◽

Vol 10 (8) ◽

pp. e0135042 ◽

Cited By ~ 5

Author(s):

Toshiki Maeda ◽

Akira Babazono ◽

Takumi Nishi ◽

Midori Yasui ◽

Shinya Matsuda ◽

...

Keyword(s):

T Cell ◽

Clinical Outcome ◽

Healthcare Resource ◽

Opportunistic Infections ◽

Cell Leukaemia ◽

The Impact

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FRI0126 POOR ADHERENCE TO METHOTREXATE IS ASSOCIATED WITH PERSISTENT DISEASE ACTIVITY DURING FOLLOW-UP FOR RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1662 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 644.1-645

Author(s):

J. H. Kang ◽

S. E. Choi ◽

H. Xu ◽

D. J. Park ◽

S. S. Lee

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Outcome ◽

Disease Activity ◽

Reactive Protein ◽

Rate Score ◽

Tertiary Center ◽

Proportion Of Days Covered ◽

Euroqol 5D ◽

Control Disease

Objectives:Although methotrexate (MTX) is the cornerstone therapy in patients with rheumatoid arthritis (RA), adherence to MTX in these patients is typically suboptimal. Thus, we investigated the proportion of RA patients who were adherent to MTX and whether non-adherence to MTX affected the clinical outcome in these patients during follow-up.Methods:We enrolled 331 RA patients from a single tertiary center. Data were collected at the time of enrollment and then annually for 4 consecutive years. Adherence was defined by the proportion of days covered at 1 year. Patients were divided into two groups: patients who took more than 80% of MTX and those who did not. Univariate and multivariate analyses were performed to identify the association between drug compliance and clinical outcome.Results:Of the 331 RA patients, 8.7% had taken less than 80% of MTX during the follow-up period. Non-adherent patients had lower EuroQol-5D scores (P=0.013) and higher RAPID3 scores (P=0.004) at baseline than adherent patients. Leflunomide was more commonly prescribed to adherent patients than non-adherent patients (P=0.012). Non-adherent patients had a higher mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate score (P=0.001), higher mean DAS28-C-reactive protein (CRP) score (P=0.001), and higher mean rate of tender and swollen joints (P=0.003 and P=0.002, respectively) than adherent patients. In the multivariate analysis, poor MTX adherence was significantly associated with a higher mean DAS28-CRP score (odds ratio, 0.270; 95% confidence interval, 0.165–0.444; P<0.001).Conclusion:Adherence to MTX can affect disease activity during follow-up in Korean patients with RA. Our results provide a rationale for patient education to maintain good drug adherence in RA patients, to control disease activity.Disclosure of Interests:None declared

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AB0254 NEUTROPHIL-LYMPHOCYTE RATIO AND PLATELET-LYMPHOCYTE RATIO IN PATIENTSRECEIVING ANTIRHEUMATIC THERAPY: RELATIONSHIP TO CLINICAL AND LABORATORY MARKERS OF DISEASE ACTIVITY

10.1136/annrheumdis-2019-eular.7762 ◽

2019 ◽

Author(s):

Iris Paola Guzmán-Guzmán ◽

Oscar Zaragoza-García ◽

José Eduardo Navarro-Zarza ◽

Isela Parra-Rojas

Keyword(s):

Disease Activity ◽

Antirheumatic Therapy ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Platelet Lymphocyte Ratio ◽

Laboratory Markers ◽

Therapy Relationship

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AB0160 Interferon-Γ-inducible kynurenines inflammation pathway: the missing link between disease activity and symptoms in sjÖgren's syndrome

10.1136/annrheumdis-2017-eular.6015 ◽

2017 ◽

Author(s):

V Valim ◽

WM Sardemberg ◽

JG Brun ◽

E Zandonade ◽

GM Balarini ◽

...

Keyword(s):

Disease Activity ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Interferon Γ ◽

Sjogren's Syndrome ◽

Missing Link ◽

Sjögren‘S Syndrome

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Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity

Leukemia ◽

10.1038/leu.2011.254 ◽

2011 ◽

Vol 26 (4) ◽

pp. 633-643 ◽

Cited By ~ 26

Author(s):

L Grkovic ◽

K Baird ◽

S M Steinberg ◽

K M Williams ◽

D Pulanic ◽

...

Keyword(s):

Disease Activity ◽

Graft Versus Host Disease ◽

Clinical Laboratory ◽

Host Disease ◽

Graft Versus Host ◽

Markers Of Inflammation ◽

Laboratory Markers

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Biomarkers associated with clinical outcome in advanced non-small cell lung cancer patients treated with TG4010

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.3027 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 3027-3027

Author(s):

B. Acres ◽

E. Quoix ◽

R. Ramlau ◽

G. Lacoste ◽

B. Marie Bastien ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Outcome ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Specific Binding ◽

Interferon Γ ◽

Small Cell ◽

Small Cell Lung ◽

Color Flow ◽

Blood Samples

3027 Background: TG4010 is a targeted immunotherapy product. It was tested in combination with first-line chemotherapy in a randomized, controlled, multicenter phase II study in patients with advanced non small cell lung cancer (NSCLC) (ASCO 2008- Abstract No 8023) Methods: In addition to clinical endpoints, immune parameters were tested. Blood samples were drawn prior to therapy (day1) as well as at day 43 (after 6 injections of TG4010). Lymphocyte populations were assessed by 5-color flow cytometry. Plasma samples were tested for biochemical markers using multi-analyte profile technology. Results: Out of the 148 patients enrolled in the study, 138 were evaluable for immunological analyses. Baseline characteristics were similar in both arms. Day 1 blood samples show: i) a correlation between lower levels of inflammation-associated plasma proteins and a longer median survival in Arm 1 (TG4010 + chemotherapy) (p< 0.001); ii) an improved clinical outcome with TG4010 in patients having normal levels of lymphocytes with an activated NK phenotype. Day 43 blood samples show: i) an association between higher levels of activated T lymphocytes and longer patient survival in Arm 1 (p < 0.05). No such association was observed in patients in Arm 2 (chemotherapy alone); ii) a longer survival for patients with higher levels of Interferon γ in Arm 1 than in Arm 2 (p=0.0001). Patients in both Arm 1 and Arm 2 showed specific binding of MUC1 tetramers to circulating CD8+ lymphocytes. No significant association between either treatment arm or clinical outcome and MUC1 tetramer binding was detected. Conclusions: These results identify the level of activated NK cells at baseline as a predictive biomarker for selection of patients to be treated with TG4010. Biomarker data including Interferon γ support a Th1 dependent pathway of activity for TG4010. [Table: see text] [Table: see text]

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Obesity Is Common in Axial Spondyloarthritis and Is Associated with Poor Clinical Outcome

The Journal of Rheumatology ◽

10.3899/jrheum.150648 ◽

2015 ◽

Vol 43 (2) ◽

pp. 383-387 ◽

Cited By ~ 33

Author(s):

Fiona Maas ◽

Suzanne Arends ◽

Eveline van der Veer ◽

Freke Wink ◽

Monique Efde ◽

...

Keyword(s):

Cohort Study ◽

Ankylosing Spondylitis ◽

General Population ◽

Clinical Outcome ◽

Disease Activity ◽

Physical Function ◽

Axial Spondyloarthritis ◽

Normal Weight ◽

Overweight And Obesity ◽

Obese Patients

Objective.To assess the prevalence of overweight and obesity in a large cohort of patients with axial spondyloarthritis (axSpA) in comparison with the general population. To explore the relationship of body mass index (BMI) with clinical outcome in axSpA.Methods.Patients from the Groningen Leeuwarden Axial SpA cohort who visited the outpatient clinic in 2011/2012 were included in this cross-sectional analysis. Body weight, height, disease activity, physical function, and quality of life (QoL) were assessed. Patients were divided into normal weight (BMI < 25 kg/m2), overweight (BMI ≥ 25 to < 30 kg/m2), and obese (BMI ≥ 30 kg/m2). BMI data for the general population in the same demographic region, matched for age and sex, were obtained from the LifeLines Cohort Study.Results.Of the 461 patients with axSpA, 37% were overweight and 22% were obese. In the LifeLines cohort (n = 136,577), 43% were overweight and 15% were obese. Overweight and obese patients were older, had longer symptom duration, and had more comorbidities, especially hypertension. Further, obese patients had significantly higher disease activity, worse physical function, and worse QoL than overweight and normal weight patients (mean Bath Ankylosing Spondylitis Disease Activity Index 4.5, 3.5, 3.8; mean Ankylosing Spondylitis Disease Activity Score 2.8, 2.2, 2.3; median C-reactive protein 5, 3, 3 mg/l; median erythrocyte sedimentation rate 13, 8, 8 mm/h; median Bath Ankylosing Spondylitis Functional Index 5.2, 2.9, 2.9; median Ankylosing Spondylitis QoL Questionnaire 8, 4, 5, respectively). After adjustment for potential confounders, obesity proved to be an independent predictor of worse clinical outcome.Conclusion.In this large observational cohort study, obesity is more common in axSpA than in the general population and it is associated with worse clinical outcome.

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