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Background: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the assessment of systemic inflammation. We aimed to evaluate suPAR for the assessment of inflammatory activity in rheumatoid arthritis (RA) patients in remission. Methods: In our cross-sectional study we measured plasma suPAR and C-reactive protein (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 120 RA patients at various stages of disease activity and 29 healthy age-matched controls. Results: suPAR, CRP and ESR values were higher in RA patients compared to healthy individuals. When suPAR levels were analyzed according to DAS28 scores of RA patients, suPAR level in the subgroup with DAS28≤2.6 was lower than in the subgroup with DAS28>2.6, but still higher than in controls [4.45 (3.33-5.56) ng/mL vs. 3.66 (3.10-4.67) ng/mL vs. 2.80 (2.06-3.42) ng/mL, p<0.0001, median (interquartile range)]. In contrast, CRP and ESR values were comparable in the subgroup with DAS28≤2.6 and in healthy individuals. We further analyzed the correlation between the number of tender and/or swollen joints and suPAR levels in RA patients in remission. suPAR values were significantly higher in patients with four tender and/or swollen joints than in patients with 2-3 or 0-1 tender and/or swollen joints. Conclusions: While CRP and ESR values indicate remission of the chronic inflammatory process in RA, suPAR values are still elevated compared to healthy individuals. suPAR might be particularly valuable in the recognition of inflammatory activity in patients who are in remission according to DAS28 scores but have symptoms of tender and/or swollen joints. [ABSTRACT FROM AUTHOR]

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients. Methods: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls. Results: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70 ng/mL to distinguish patients with high disease activity (SLEDAI >8). Conclusion: suPAR might be an objective marker for identifying SLE patients with active disease. [ABSTRACT FROM AUTHOR]

The mechanisms of endotoxin tolerance (ET), which down-regulate inflammation, are well described in response to exogenous toll-like receptor ligands, but few studies have focused on ET-associated mechanisms in inflammatory disease. As blocking TNF can attenuate the development of ET, the effect of anti-TNF on the expression of key ET-associated molecules in inflammatory auto-immune disease was measured; changes in inflammatory gene expression were confirmed using an ET bioassay. The expression of immunomodulatory molecules was measured in a murine model of arthritis treated with anti-TNF and the expression of ET-associated molecules was measured in whole blood in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients, before and after therapy. The expression of ET-associated genes was also measured in RA patient monocytes before and after therapy, in anti-TNF responders and non-responders. Tnfaip3 , Ptpn6 and Irak3 were differentially expressed in affected paws, spleens, lymph nodes and circulating leucocytes in experimental murine arthritis treated with anti-TNF. Prior to therapy, the expression of TNFAIP3 , INPP5D , PTPN6, CD38 and SIGIRR in whole blood differed between human healthy controls and RA or AS patients. In blood monocytes from RA patients, the expression of TNFAIP3 was significantly reduced by anti-TNF therapy in non-responders. Prior to therapy, anti-TNF non-responders had higher expression of TNFAIP3 and SLPI , compared to responders. Although the expression of TNFAIP3 was significantly higher in RA non-responders prior to treatment, the post-treatment reduction to a level similar to responders did not coincide with a clinical response to therapy. • An endotoxin tolerance (ET) bioassay links phenotypes with gene expression profiles. • ET-associated mechanisms associate with disease status and anti-TNF response. • Prior to treatment, TNFAIP3 expression is higher in anti-TNF non-responders. [ABSTRACT FROM AUTHOR]

Résumé: Des études récentes ont démontré que le récepteur soluble de l’urokinase plasminogène activateur (suPAR) est un marqueur précieux à la reconnaissance d’une réponse inflammatoire. Une inflammation en cours entraîne des taux plasmatiques élevés de suPAR. Notre objectif était de définir les taux plasmatiques de suPAR chez les patients atteints de spondylarthrite ankylosante (SA) face à des individus sains afin de montrer que le suPAR pourrait être utilisé comme marqueur clinique de l’inflammation dans la SA. Nous avons mesuré les taux plasmatiques de suPAR et de la protéine C réactive (CRP) ainsi que la vitesse de sédimentation des hématies (VSH) chez 33 patients atteints de SA à différents stades de durée de la maladie et de son activité et de même chez 29 témoins sains. Les valeurs de la CRP et de la VSH étaient plus élevées chez les patients atteints de SA que chez les individus sains, alors que les valeurs de suPAR étaient comparables (médiane [intervalle interquartile] : 2,97 [2,57–3,80] ng/mL versus 2,80 [2,06–3,42] ng/mL, p >0,05). Chez les patients atteints de SA, une corrélation a été détectée entre les scores d’indice d’activité de la spondylarthrite ankylosante (BASDAI) et la CRP ainsi qu’avec les valeurs de la VSH, mais pas en lien avec les taux de suPAR (p =0,0005, r =0,57 et p =0,01, r =0,43, respectivement). Contrairement à beaucoup d’autres maladies inflammatoires, les taux plasmatiques de suPAR ne reflètent pas d’inflammation dans la SA. Afin d’évaluer l’état inflammatoire dans la SA, les valeurs de la VSH et particulièrement celles de la CRP sont encore des marqueurs cliniques plus appropriés. Dans la lignée de découvertes antérieures, nos résultats indiquent que, contrairement au suPAR, ces deux marqueurs sont positivement liés à l’activité de la maladie dans la SA. [Copyright &y& Elsevier]

The role of the innate immune system has been established in the initiation and perpetuation of inflammatory disease, but less attention has been paid to its role in the resolution of inflammation and return to homeostasis. Toll-like receptor (TLR) expression profiles were analysed in tissues with differing disease status in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and in experimental arthritis. TLR gene expression was measured in whole blood and monocytes, before and after TNF blockade. In RA and osteoarthritis synovia, the expression of TLRs was quantified by standard curve qPCR. In addition, four distinct stages of disease were defined and validated in collagen-induced arthritis (CIA), the gold standard animal model for RA – pre-onset, early disease, late disease and immunised mice that were resistant to the development of disease. TLR expression was measured in spleens, lymph nodes, blood cells, liver and the paws (inflamed and unaffected). In RA whole blood, the expression of TLR1, 4 and 6 was significantly reduced by TNF blockade but the differences in TLR expression profiles between responders and non-responders were less pronounced than the differences between RA and AS patients. In RA non-responders, monocytes had greater TLR2 expression prior to therapy compared to responders. The expression of TLR1, 2, 4 and 8 was higher in RA synovium compared to control OA synovium. Circulating cytokine levels in CIA resistant mice were similar to naïve mice, but anti-collagen antibodies were similar to arthritic mice. Distinct profiles of inflammatory gene expression were mapped in paws and organs with differing disease status. TLR expression in arthritic paws tended to be similar in early and late disease, with TLR1 and 2 moderately higher in late disease. TLR expression in unaffected paws varied according to gene and disease status but was generally lower in resistant paws. Disease status-specific profiles of TLR expression were observed in spleens, lymph nodes, blood cells and the liver. Notably, TLR2 expression rose then fell in the transition from naïve to pre-onset to early arthritis. TLR gene expression profiles are strongly associated with disease status. In particular, increased expression in the blood precedes clinical manifestation. • TLR expression profiles are strongly correlated with disease status. • 'Resistant' endophenotype with auto-antibodies exhibits distinct transcriptome. • An increase in circulating leukocyte TLR expression presages disease onset. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies demonstrated that soluble urokinase plasminogen activator receptor (suPAR) is a valuable marker in the recognition of an inflammatory response. Ongoing inflammation leads to elevated plasma suPAR levels. We aimed to characterize plasma suPAR levels in ankylosing spondylitis (AS) patients compared to healthy individuals in order to reveal if suPAR could be used as a clinical marker of inflammation in AS. We measured plasma suPAR and C-reactive protein (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 33 AS patients at various stages of disease duration and activity and 29 healthy controls. CRP and ESR values were higher in AS patients than in healthy individuals, while suPAR values were comparable (median [interquartile range]: 2.97 [2.57–3.80] ng/mL vs. 2.80 [2.06–3.42] ng/mL, P >0.05). In AS patients, a correlation was detected between BASDAI scores and CRP as well as ESR values but not suPAR levels (P =0.0005, r =0.57 and P =0.01, r =0.43, respectively). Unlike in many other inflammatory conditions, plasma suPAR levels do not reflect inflammation in AS. To assess the inflammatory status in AS, ESR and particularly CRP values are still more appropriate clinical markers. In line with earlier findings, our results indicate that, unlike suPAR, both of these markers are positively correlated with disease activity in AS. [Copyright &y& Elsevier]