Abstract
IntroductionLeptin has a prominent role in the development and maintenance of acute and chronic inflammatory states such as rheumatoid arthritis (RA) and obesity. Nevertheless, the association of serum leptin (sLep) and soluble leptin receptor (sLepR) in RA pathogenesis has not been clarified. The purpose of this study was to evaluate the association of sLep, sLepR and leptin production indexes such as sLep/fat mass ratio with clinical activity and biomarkers and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA compared with body mass index (BMI) matched control subjects.MethodsWe included 64 RA patients and 66 controls matched for age, gender and BMI. Subjects were evaluated for BMI, fat mass distribution, sLep, sLepR, sLep/fat mass ratio and sLepR/fat mass ratio. Patients were evaluated for clinical activity and anti-CCP antibodies.ResultsWe found two or three fold increased sLep levels, sLep/sLepR ratio and sLep/fat mass ratio in obese anti-CCP positive RA patients vs. controls. Partial correlations showed that anti-CCP antibodies were correlated with sLep/fat mass ratio (partial r = 0.347, P = 0.033) after adjustment for age, subcutaneous adipose tissue and fat mass.ConclusionsIn preobese and obese RA patients there is and increased production of sLep according to anti-CCP positivity. This phenomenon suggests there is an additive effect of chronic inflammation resulting from RA and obesity in which leptin favors the humoral response against citrullinated proteins. In summary, the data observed in our study suggests sLep could be a surrogate marker of chronicity and humoral immunity in RA in the presence of obesity.
Highlights
Leptin has a prominent role in the development and maintenance of acute and chronic inflammatory states such as rheumatoid arthritis (RA) and obesity
We evaluated RA patients without traditional cardiovascular risk factors classified by anti-cyclic citrullinated peptide positivity, measuring serum leptin, soluble leptin receptor (sLepR), sLep/sLepR ratio and other metabolic parameters, namely proinflammatory cytokines, body mass index (BMI) and adiposity
Demographic and clinical characteristics We evaluated 64 RA patients compared with 66 controls matched by age and gender, classified according to BMI
Summary
Leptin has a prominent role in the development and maintenance of acute and chronic inflammatory states such as rheumatoid arthritis (RA) and obesity. The association of serum leptin (sLep) and soluble leptin receptor (sLepR) in RA pathogenesis has not been clarified. Adipokines have gained a prominent role within the last decade in the understanding of pathogenesis of chronic diseases (RA, obesity, metabolic syndrome and type 2 diabetes mellitus) [1, 3], through the maintenance of chronic inflammation within the joints or systemically [4]. Five isoforms of LepR in humans have been described; the isoforms “a” through “d”, are transmembrane proteins obtained by alternative splicing, while, isoform “e” corresponds to soluble leptin receptor (sLepR) obtained by proteolytic shedding of transmembrane isoforms [8]
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