Clinical Characteristics and Cytokine Profiles of Organizing Pneumonia in Patients with Rheumatoid Arthritis Treated with or without Biologics

Objective.It has been reported that organizing pneumonia (OP) develops when patients with rheumatoid arthritis (RA) are treated with biologic disease-modifying antirheumatic drugs (bDMARD). However, the clinical characteristics and pathophysiology of OP in RA remain unknown in patients treated with bDMARD. We investigated the clinical characteristics and cytokine profiles of patients with RA-OP treated with bDMARD or conventional synthetic DMARD (csDMARD).Methods.Twenty-four patients with RA who had developed OP were enrolled. These patients included 12 treated with bDMARD (bDMARD-OP subset) and 12 treated with csDMARD (csDMARD-OP subset). We compared the clinical characteristics and cytokine profiles between the patients with OP (OP subset, n = 24) and non-OP patients (non-OP subset, n = 29).Results.There was no significant difference in clinical characteristics between the OP subset and the non-OP subset. Four patients developed OP within 2 months of bDMARD administration. In the other 8 patients, OP developed more than 1 year after the initiation of bDMARD. OP improved with corticosteroid treatment in all bDMARD-OP patients. After OP improved, bDMARD were readministered in 6 patients, and no OP recurrence was observed in any of these patients. Our multivariate analysis revealed that serum levels of interferon-α (IFN-α), interleukin (IL)-1β, IL-6, IL-8, and interferon-γ–inducible protein 10 were significantly associated with the development of OP, although these cytokines tended to be lower in the bDMARD-OP subset than in the csDMARD-OP subset.Conclusion.OP is unlikely to be fatal in patients treated with bDMARD or csDMARD. IFN-α and proinflammatory cytokines are associated with the pathophysiology of OP in RA.

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Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases

The Journal of Rheumatology ◽

10.3899/jrheum.090662 ◽

2010 ◽

Vol 37 (5) ◽

pp. 967-973 ◽

Cited By ~ 56

Author(s):

JUNKO MARUYAMA ◽

SHIGEKO INOKUMA

Keyword(s):

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Laboratory Data ◽

Serum Levels ◽

Interferon Γ ◽

Cytokine Profiles ◽

Factor Α ◽

Activation Syndrome

Objective.To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis.Methods.The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-α, interleukin 6, interferon-γ, ferritin, and ß2-microglobulin (ß2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered.Results.Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still’s disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and ß2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; ß2m: 18.8 vs 5.4 mg/dl, p = 0.0058).Conclusion.The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ß2m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.

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Elevated Serum Levels of Interferon‐γ–Inducible Protein–10 in Patients Coinfected with Hepatitis C Virus and HIV

The Journal of Infectious Diseases ◽

10.1086/520935 ◽

2007 ◽

Vol 196 (7) ◽

pp. 1053-1057 ◽

Cited By ~ 53

Author(s):

Barbara Roe ◽

Suzie Coughlan ◽

Jaythoon Hassan ◽

Anne Grogan ◽

Gillian Farrell ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Elevated Serum ◽

Serum Levels ◽

Interferon Γ ◽

Inducible Protein

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Increased serum levels of interferon-γ -inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis

Clinical & Experimental Immunology ◽

10.1046/j.1365-2249.2003.02237.x ◽

2003 ◽

Vol 133 (3) ◽

pp. 448-453 ◽

Cited By ~ 42

Author(s):

H. TAKADA ◽

Y. TAKAHATA ◽

A. NOMURA ◽

S. OHGA ◽

Y. MIZUNO ◽

...

Keyword(s):

Serum Levels ◽

Interferon Γ ◽

Gamma Interferon ◽

Haemophagocytic Lymphohistiocytosis ◽

Inducible Protein

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Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis

Rheumatology International ◽

10.1007/s00296-009-1356-y ◽

2010 ◽

Vol 30 (6) ◽

pp. 725-730 ◽

Cited By ~ 11

Author(s):

Tetsuya Ichikawa ◽

Yasunori Kageyama ◽

Hayato Kobayashi ◽

Norihiko Kato ◽

Kunio Tsujimura ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interferon Gamma ◽

Serum Levels ◽

Etanercept Treatment ◽

Interleukin 15 ◽

Inducible Protein

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FRI0105 EVALUATION OF CXCL13 AND ICAM1 SERUM LEVELS AS PREDICTORS OF CLINICAL RESPONSE TO ABATACEPT IN RHEUMATOID ARTHRITIS.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3761 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 632.2-632

Author(s):

S. Piantoni ◽

S. Masneri ◽

F. Regola ◽

C. Nalli ◽

A. Tincani ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Response ◽

Synovial Fibroblasts ◽

Serum Levels ◽

Response To Treatment ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Entire Cohort ◽

Significant Difference ◽

Before And After

Background:Soluble intercellular adhesion molecule 1 (ICAM1) and C-X-C motif chemokine 13 (CXCL13) were described as differentially associated with two major subtypes of synovitis in rheumatoid arthritis (RA). Raised serum levels of ICAM1 (which is upregulated in synovial fibroblasts in response to TNFα), and of CXCL13 (which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells), are associated with a myeloid or lymphoid synovial phenotype, respectively (1). It has been suggested that a preferential clinical response to anti-TNFα, as compared to anti-IL-6R monotherapy, can be predicted by measuring these two biomarkers (2). No information is available on the possible utility of these biomarkers in RA patients treated with abatacept (ABA), a T-cell co-stimulation blocker.Objectives:To analyze the effect of ABA on ICAM1 and CXCL13 serum levels in RA and to verify whether they predict the response to the drug.Methods:63 RA patients [F/M=51/12; median (10th-90thpercentile) age=60 (41-72) years; CRP-DAS28=4.6 (3.3-5.8); ACPA positive: 86%], before and after 6 months of treatment with ABA + methotrexate and 22 sex and age-matched healthy controls (HC) were evaluated. Serum ICAM1 and CXCL13 levels were dosed by commercial ELISA (Life Technologies and R&D). Response to treatment was defined with the EULAR criteria.Results:CXCL13 serum levels were higher in RA at baseline than in HC [136 (42-325) vs 32 (19-57) pg/ml, p<0.01], while no difference was observed in ICAM1 [186 (125-276) vs 184 (153-246) ng/ml, p=0.9]; positive correlations between ICAM1 and CRP (r:0.28; p=0.03) and CXCL13 levels and CRP (r:0.40; p<0.01) and CRP-DAS28 values (r:0.27, p=0.05) were found. After therapy with ABA, a reduction of CXCL13 was observed [136 (42-325) vs 94 (29-319) pg/ml, p<0.01], both in responders [n: 37: 151 (57-462) vs 97 (26-329) pg/ml; p<0.01] and non-responders (n: 14: 142 (68-293) vs 89 (42-198) pg/ml; p=0.01]. Not significant variation of ICAM1 serum levels was found in the entire cohort [186 (125-276) vs 190 (113-252) ng/ml, p=0.06]. However, a significant decrease was observed in non-responders [222 (169-302) vs 186 (110-233) ng/ml, p=0.02]. At baseline, no significant difference was found among patients seropositive for ACPA if compared with the negative ones [ACPA+ vs ACPA- for ICAM1 [187 (123-280) vs 177 (134-258) ng/ml; p=0.7] and for CXCL13 [143 (42-368) vs 113 (56-270) pg/ml; p=0.4]].Conclusion:Our results confirmed that CXCL13 serum levels are directly correlated with disease activity and demonstrated that ABA therapy induces their reduction. These findings suggest that the co-stimulation blockade at central level and/or in the synovium lead to a reduced production of CXCL13. We could not demonstrate that CXCL13 levels predict the clinical response to ABA in this cohort of patients.References:[1]Rosengren S, Rheumatology 2011;2.Dennis G, Arthritis Res Ther 2014Acknowledgments:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduction.Disclosure of Interests:None declared

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The role of alpha-2-macroglobulin in pathogenesis of rheumatoid arthritis and system lupus erythematosus

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2010-5-39-44 ◽

2010 ◽

Vol 9 (5) ◽

pp. 39-44

Author(s):

V. N. Zorina ◽

I. G. Kozlov ◽

R. M. Zorina ◽

N. A. Trofimenko ◽

T. S. Chirikova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Progression ◽

Acute Phase ◽

Lupus Erythematosus ◽

Acute Phase Proteins ◽

Serum Levels ◽

Control Group ◽

Healthy Donors ◽

Significant Difference

We investigated serum levels of alpha-2-macroglobulin (α2—MG) and some of its complexes, namely α2-MG-plasmin (α2-MG— Pl) and α2-MG—IgG at a rheumatoid arthritis (RA) 2—3 degrees of activity (65 patients), a system lupus erythematosus (SLE) of 2-3 degrees of activity (30 patients) and 55 healthy donors as a control group. It is shown, that at SLE the total level of α2-MG is invariable, and at RA — decreases significantly in comparison with the healthy. The concentration of complexes was raised at pathology, but at RA this rising was expressed much more strongly, than at SLE. At studying of correlations of levels of α2-MG, α2-MG—Pl and α2-MG— IgG among themselves and with some several cytokines and acute phase proteins, it is shown, that there is some significant difference between normal and pathological correlative relations and allows us to suspect that at SLE, the α2-MG and its complexes participate in a pathogenesis, and at RA α2-MG becomes the major immunogenesis factor and the significant reason of disease progression.

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A Pilot Study to Evaluate the Effects of Oral N-Acetyl Cysteine on Inflammatory and Oxidative Stress Biomarkers in Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573403x14666180926100811 ◽

2019 ◽

Vol 15 (3) ◽

pp. 246-253 ◽

Cited By ~ 3

Author(s):

Ghazal Hashemi ◽

Mahtabalsadat Mirjalili ◽

Zahra Basiri ◽

Ahmad Tahamoli-Roudsari ◽

Nejat Kheiripour ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Placebo Group ◽

Inflammatory Cytokines ◽

Serum Levels ◽

Stress Factors ◽

Oxidative Stress Biomarkers ◽

Significant Difference ◽

Acetyl Cysteine ◽

And Oxidative Stress

Background: Rheumatoid Arthritis (RA) is a common inflammatory disease of the joints. Due to the importance of inflammation and oxidative stress in the pathogenesis of RA, drugs that have anti-oxidant and anti-inflammatory properties, such as N-acetyl Cysteine (NAC), can be used as adjunctive therapy in patients with RA. Aims: The aim of this study was to evaluate the effects of oral NAC on inflammatory cytokines and oxidative stress in patients with RA. Methods: Adjunct to standard treatment, the NAC group (23 patients) received 600 mg of NAC twice daily and the placebo group (19 patients) received identical placebo twice daily for 12 weeks. Serum levels of Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), nitric oxide (NO), Total Thiol Groups (TTG), Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6), C-reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR) were measured at baseline and at the end of the study. Results: Results showed that in the NAC group, the serum levels of MDA, NO, IL-6, TNF-α, ESR and CRP were significantly lower than the baseline. Also, the serum level of TAC and TTG, as antioxidant parameters, increased significantly. However, only NO, MDA and TTG showed a significant difference in the NAC group as compared to the placebo group at the end of study. Conclusion: According to the results of this study, oral NAC can significantly reduce the several oxidative stress factors and inflammatory cytokines. These results need to be confirmed in larger studies while considering clinical outcomes of RA patients.

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Similar Serum Levels of IL-6 and its Soluble Receptors in Patients with HCV-Related Arthritis and Rheumatoid Arthritis: A Pilot Study

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201202500132 ◽

2012 ◽

Vol 25 (1) ◽

pp. 281-285 ◽

Cited By ~ 8

Author(s):

A. Riccio ◽

L. Postiglione ◽

P. Sabatini ◽

M. Linvelli ◽

I. Soriente ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Pilot Study ◽

Healthy Subjects ◽

Serum Levels ◽

High Serum ◽

Control Group ◽

Serum Concentrations ◽

Soluble Receptors ◽

Significant Difference

The high serum levels of Interleukin-6 (IL-6) and its soluble receptors (sIL-6r and sgp 130), described in the course of Rheumatoid Arthritis (RA), have been linked to the enhanced activity of this cytokine in this disorder. In this study, the serum concentrations of IL-6 and its soluble receptors were determined in a group of patients with HCV-related arthritis (HCVrA), a condition resembling RA in several aspects, and then compared to those found in a sample of subjects affected by RA. Twenty-one patients with HCVrA, 24 patients with RA and 20 healthy subjects (control group) were examined. Different ELISA methods were used for determination of serum concentrations of IL-6, sIL-6r and sgp 130. Increased IL-6 serum levels were found in 15 (71%) of the patients with HCVrA and in 16 (62%) of those with RA. Eight (38%) of the patients with HCVrA and 11 (46%) of those with RA denoted high levels of sIL-6r, while sgp 130 levels were elevated in 21 (76%) of the patients with HCVrA and in 16 (69%) of those with RA. A significant difference between the median values of sIL-6r and sgp 130 levels in the two groups of patients versus controls was found. A mild correlation of these parameters with RF levels was detected in the RA group. Furthermore, in HCVrA patients the serum levels of IL-6, sIL-6r and sgpl30 appeared unrelated to HCV viraemia and to levels of transaminases. The enhanced serum levels of IL-6 in HCVra patients indicate an increased synthesis and hyperactivity of this cytokine in HCVrA, and the substantial similarity of the behaviour of IL-6 and its serum receptors in the two groups of patients suggests common mechanisms with RA, in which the function of IL-6 is central.

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Comparation between serum levels of interleukin-33 in children with allergic asthma before and after inhalatory corticosteroid treatment

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh190605126m ◽

2020 ◽

Vol 148 (5-6) ◽

pp. 304-309

Author(s):

Borko Milanovic ◽

Gordana Vijatov-Djuric ◽

Jelena Stojcevic-Maletic ◽

Vesna Stojanovic

Keyword(s):

Allergic Asthma ◽

Corticosteroid Treatment ◽

Allergic Diseases ◽

Serum Levels ◽

Healthy Children ◽

Interleukin 33 ◽

Significant Difference ◽

Before And After ◽

Applied Dose ◽

And Control

Introduction/Objective. Interleukin 33 (IL-33) has a very significant function in inflammatory and autoimmune mechanisms, but its significance in immunopathogenic mechanisms of different allergic diseases, including allergic asthma (AA), is becoming increasingly emphasized. The objective of the study was to investigate serum levels of IL-33 in children with AA before applying inhalation corticosteroid therapy (ICS Th) and six months after it, correlating the gathered values of IL-33 with some clinical traits of the patient. Methods. The serum value of IL-33 has been determined in 61 children with AA before starting treatment and six months after treatment with ICS Th, and this was repeated in 30 healthy children. Results. Values of IL-33 in serum are significantly higher in children with AA that have not been treated with ICS Th during six months (p = 0.00; p < 0.05), which is also the case when comparing with healthy children (p = 0.00; p < 0.05). Serum values of IL-33 in children with AA after six months of ICS Th and in healthy children do not show significant difference (p = 0.88; p > 0.05). The correlation between serum values of IL-33 before applying ICS Th and the severity, degree of AA control, and the applied dose of ICS Th is statistically significant and positive. Conclusion. IL-33 values in the serum are significantly higher in children with untreated AA in those with poorly controlled AA. Six-month treatment with ICS Th leads to significant reduction of IL-33 serum levels, whose values are in positive correlation with the severity and control of AA.

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