Baseline Serum Adipokine Click to edit Master Levels subtitle style Predict Radiographic Progression in Early Rheumatoid Arthritis

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Introduction
Background:
Rheumatoid arthritis (RA) is defined as a

chronic inflammatory systemic disease characterised by symmetrical deforming polyarthritis and extra-articular manifestations.

Chronic inflammatory processes lead to

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cartilage damage and bone erosions, resulting in destruction of the total joint architecture.

Introduction
Why is research on rheumatoid arthritis important?
Rheumatoid arthritis is a very common

condition and has a prevalence of 1% of the general population of the United Kingdom.

The distribution of this condition is worldwide. This condition is responsible for a high 4/29/12

Introduction
Rheumatoid arthritis therefore places a great

burden, both financial and otherwise, on society as a whole.

It is therefore important to ensure that this

condition is understood so that it can be treated.

By doing this, morbidity and the burden

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on society can be reduced.

Introduction
Previous research on rheumatoid arthritis has

been done by Combe et al. (2001) and Van der Helm-van Mil et al. (2005).
This research has shown that more rapid

progression of the disease is associated with markers of inflammation, such as the ESR, as well as the presence of anti-CCP antibodies.
Research has also been conducted that shows

an inverse 4/29/12

correlation between BMI (body

Introduction
Adipokines have been shown to play a pro

inflammatory role in joint physiology.

Adipokines are the soluble mediators

(cytokines) that were initially thought to only be secreted by adipose tissue but are now known to be secreted by several cell types including cells present in the joint.

They include TNF , IL-6, leptin, resistin,

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and adiponectin.

Introduction
This paper by Klein-Wieringa et al. further

examines potential role by looking at whether adipokines affect the radiographic progression in rheumatoid arthritis.
This paper investigated whether serum

adipokine levels at baseline were able to predict radiographic damage over a period of 4 years independently of other potent predictors for progression, such as BMI and the presence of anti-CCP antibodies.
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Method
253 patients participating in the Leiden Early

Arthritis Cohort (EAC) were included in this study.

All patients must have met the American

College of Rheumatology (ACR) 1987 revised criteria for the classification of RA within the first year of follow up.

Radiographs of the hands and feet were

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obtained at baseline and yearly thereafter. They were scored in chronologic order for

Method
All radiographs were scored by one

experienced scorer who was blinded with respect to the patients autoantibody status, treatment, and clinical outcome..
Analysis of radiographic progression stratified

for the year of inclusion was then carried out. This identified that there were 3 distinct groups of patients present who had different treatment strategies.

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Method
Serum samples were obtained at baseline and

stored at - 80C.

Patients were excluded from this study if they

were being treated with anti-rheumatic drugs when serum samples were obtained.

The ESR (mm/hour) and the serum CRP level

(mg/litre) were measured at the Clinical and 4/29/12 Chemical laboratory at the Leiden University

Method
Anti-CCP antibody levels were measured using

enzyme-linked immunosorbent assays (EuroDiagnostica), with seropositivity defined above a cut-off level of 25 units.

The concentrations of serum adipokines

(leptin, adiponectin, adipsin, visfatin, resistin, IL-6, and TNF were then measured.
4/29/12 The Bio-Plex Pro Human Diabetes kit, the Bio-

Method
The BMI was normally distributed in the study

population. Correlations between BMI, inflammation markers, and adipokine levels were calculated using Spearmans rank correlation test.
The association between adipokine levels at

baseline and the rate of radiographic progression over 4 years was tested using a multivariate normal regression model.
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Method
Adipokine levels, except for adiponectin and

adipsin, as well as Sharp/van der Heijde scores, were logarithmically transformed to meet the assumptions of linear regression.

The estimates resulting from the analyses

were then recalculated to reflect the relationship between radiographic progression and adipokine levels rather than the relationship between their log-transformed 4/29/12 values.

Method
The Z statistic was used to compare

estimates between groups, and a Z score greater than or equal to 1.96 was considered significant.

SPSS version 17.0 was used to analyse the

data. Bonferroni correction was performed when assessing the significance of the studied associations..

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Results

Refer to

Table 1, which
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Results
Using a multivariate normal regression model,

the association between ESR, the CRP level, BMI, and the presence of anti-CCP antibodies, and radiographic progression was investigated.

Refer to Figure 1 and Table 2 for the specific

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associations between baseline adipokine levels and the rate of radiographic progression over 4 years.

Results
However, only adiponectin levels remained

significantly associated with radiographic progression when the model was corrected for the presence of anti-CCP antibodies, whereas a trend was observed for IL-6.
The association of both TNF and visfatin with

radiographic damage disappeared after correction for the presence of anti-CCP antibodies.
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Conclusions
Based on the results obtained during the

course of this study, it was concluded in this paper that adipokines are predictors of radiographic progression in RA.

It was speculated that this might be through

distinct underlying biologic mechanisms.

These mechanisms are yet to be fully

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understood.

Conclusions
A further conclusion formed was that an

antibody-independent association was shown for adiponectin.

This is described to be a very important

association as it suggests that this adipokine may potentially be a valuable prediction marker for radiographic joint damage and disease progression in patients with early RA.

This means that treatments, affecting this 4/29/12

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