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Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

ABSTRACT: Pro- and anti-inflammatory mediators, such as IL-1? and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA).111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collection at 6-month intervals. The plasma biochemical marker IL1Ra was assessed at baseline and 18 months; other plasma biochemical markers were assessed only at 18 months, including IL-1?, TNF?, VEGF, IL-6, IL-6R?, IL-17A, IL-17A/F, IL-17F, CRP, sTNF-RII, and MMP-2.In cross-sectional studies, WOMAC (total, pain, function) and plasma IL1Ra were modestly associated with radiographic severity after adjustment for age, gender and body mass index (BMI). In addition, elevation of plasma IL1Ra predicted joint space narrowing (JSN) at 24 months. BMI did associate with progression in some but not all analyses. Causal graph analysis indicated a positive association of IL1Ra with JSN; an interaction between IL1Ra and BMI suggested either that BMI influences IL1Ra or that a hidden confounder influences both BMI and IL1Ra. Other protein biomarkers examined in this study did not associate with radiographic progression or severity.Plasma levels of IL1Ra were modestly associated with the severity and progression of SKOA in a causal fashion, independent of other risk factors. The findings may be useful in the search for prognostic biomarkers and development of disease-modifying OA drugs.

SUBMITTER: Attur M

PROVIDER: S-EPMC4630783 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

Attur M M Statnikov A A Samuels J J Li Z Z Alekseyenko A V AV Greenberg J D JD Krasnokutsky S S Rybak L L Lu Q A QA Todd J J Zhou H H Jordan J M JM Kraus V B VB Aliferis C F CF Abramson S B SB

Osteoarthritis and cartilage 20151101 11

<h4>Objective</h4>Pro- and anti-inflammatory mediators, such as IL-1β and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA).<h4>Design</h4>111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collec ...[more]

PMID: 26521737

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Project description:BackgroundOsteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation.Materials and methodsThe type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.ResultsIn both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011).ConclusionSerum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.Level of evidenceLevel III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

Project description:BackgroundThe long-term prevalence of knee osteoarthritis (OA) after anterior cruciate ligament (ACL) injury is unknown, especially in patients without a history of ACL surgery.PurposeTo (1) describe the prevalence of radiographic OA, symptomatic OA, and knee replacement surgery 32 to 37 years after acute ACL injury and to (2) compare the prevalence of radiographic OA, symptomatic OA, and knee symptoms between patients allocated to early ACL surgery or no ACL surgery and patients who crossed over to ACL surgery.Study designCohort study; Level of evidence, 2.MethodsParticipants aged 15 to 40 years at the time of ACL injury were allocated to surgical (augmented or nonaugmented ACL repair) or nonsurgical ACL treatment within 14 days of injury. At 32 to 37 years after the initial injury, 153 participants were followed up with plain weightbearing radiographs and completed 4 subscales from the Knee injury and Osteoarthritis Outcome Score (KOOS). Radiographic OA was defined as Kellgren and Lawrence grade 2 or higher. Symptomatic OA was defined as radiographic OA plus knee symptoms measured with the KOOS.ResultsParticipants allocated to ACL surgery (n = 64) underwent surgery at a mean ± SD of 5 ± 4 days (range, 0-11 days) after injury. Of the 89 participants allocated to no ACL surgery, 53 remained nonsurgically treated, 27 had ACL surgery within 2 years, and 9 had ACL surgery between 3 and 21 years after injury. In the total sample, 95 participants (62%) had radiographic tibiofemoral OA, including 11 (7%) who had knee replacement. The prevalence of radiographic tibiofemoral OA was lower in the group allocated to ACL surgery compared with the group who never had ACL surgery (50% vs 75%; P = .005). The prevalence of symptomatic OA (50% in the total sample) and patellofemoral radiographic OA (35% in the total sample) was similar between groups.ConclusionPatients allocated to early ACL surgery, performed a mean 5 days after injury, had a lower prevalence of tibiofemoral radiographic OA at 32 to 37 years after injury compared with patients who never had ACL surgery. The prevalences of symptomatic OA, radiographic patellofemoral OA, and knee symptoms were similar irrespective of ACL treatment. Overall, the prevalence of OA after ACL injury was high.RegistrationNCT03182647 (ClinicalTrials.gov identifier).

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Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

Publications

Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

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