Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis

Background:In recent years, the relationship between obesity and autoimmune diseases has taken interest, since adipose tissue has been identified as an endocrine organ that secretes cytokines (adipokines), among which leptin stands out as a soluble pro-inflammatory mediator associated with the body mass index (BMI).Objectives:The main objectives of this study are: i) to analyse the influence of BMI on clinical response in Rheumatoid Arthritis (RA) patients who initiate TNF-inhibitor (TNFi) therapy; ii) to analyse the differences in the serum profile of adipokines (leptin and adiponectin) according to BMI and their association with response to treatment.Methods:Observational study of a prospective cohort of 73 RA patients who initiated biological treatment with TNFi from the Complex Therapy Unit (CTU) of our Hospital. Patients were classified according to their BMI in normal-weight (BMI<25) and overweight/obesity (O/O) (IMC≥25). Demographic, clinical and laboratory variables were collected at baseline and at 6 months. Our outcome measures were DAS28-VSG remission (DAS28<2.6) at 6 months after TNFi initiation. Serum leptin and adiponectin levels were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA) at baseline and 6 months. A descriptive sample analysis comparing the characteristics of both patient subgroups was performed using Chi-square, T-test for independent samples and U-Mann Whitney. Likewise, a bivariate analysis was carried out by means of binary logistic regression to assess the probable association of the parameters studied with remission.Results:Of the 73 patients studied, 51% were classified in O/O group. The O/O patients presented higher levels of baseline CRP (16.69±6.16 vs 8.74±3.81, p=0.01). No statistically significant differences were observed in the remaining variables (sex, age at the beginning of the TNFi, disease duration, baseline DAS-28), as well as therapeutic variables (use of previous DMARDs and doses of methotrexate and/or steroids). Patients with overweight/obesity presented higher DAS28-ESR values at 6 months of treatment (3.59±1.14 vs 2.93±1.27, p=0.02) and achieved remission less frequently (18.9% vs 48.6%, p=0.007). Serum leptin levels were significantly higher in O/O patients, both baseline (29.39±21.50 vs 13.49±8.78, p<0.001) and 6 months (33.06±22.03 vs 14.77±9.50, p<0.001) after TNFi initiation. In addition, O/O patients were less likely to reach remission at 6 months than normal-weight patients. [OR= 4.04 IC95% (1.40-11.64); p=0.009]. Lower frequency of remission was associated to greater leptin levels at 6 months [OR=0.94 CI95% (0.90-098); p=0.012]. No differences in serum adiponectin were found between both subgroups of patients.Conclusion:In this RA patient cohort, overweight/obesity is associated with i) a reduced response to TNFi therapy and ii) a lower short-term remission rate. Within the adipokine profile, leptin seems to play a relevant role in the maintenance of pro-inflammatory activity with a negative influence on the response to TNFi therapy in O/O patients.References:[1] Versini M. et al. Autoimmun Rev. 2014; 13, 981-1000[2] Toussirot E et al. Life Sci. 2015;140: 29-36.Disclosure of Interests:Marta Novella-Navarro: None declared, Borja Hernández-Breijo: None declared, Fernanda Genre: None declared, Leticia Lera-Gómez: None declared, Verónica Pulito-Cueto: None declared, Laura Nuño: None declared, Alejandro Villalba: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Chamaida Plasencia: None declared

Download Full-text

AB0304 IMMUNOGENICITY OF BIOLOGIC DRUGS IN THE CLINICAL PRACTICE IN THE BULGARIAN POPULATION OF PATIENTS SUFFERING FROM RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.923 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1451.3-1451

Author(s):

K. Kraev ◽

M. Geneva-Popova ◽

S. Popova

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Clinical Response ◽

Neutralizing Antibodies ◽

Tnf Alpha ◽

Drug Bioavailability ◽

Drug Induced ◽

Etanercept Treatment ◽

Markers Of Inflammation

Background:Biological drugs are protein derivatives that, as such, are highly immunogenic. In recent years there have been many conflicting opinions about the role of drug immunogenicity in clinical practice.Objectives:To evaluate the drug immunogenicity of TNF-alpha blocking drugs (etanercept and adalimumab) used to treat patients with rheumatoid arthritis. To determine whether their presence can alter the effect of treatment and to evaluate their role in the clinical practice of rheumatologists.Methods:121 patients with rheumatoid arthritis, as well as 31 healthy controls, similar in sex and age, were examined. They were all monitored at 0, 6, 12 and 24 months from the start of TNF-alpha blocker treatment. Demographics, vital signs, markers of inflammation such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity indices were examined at each visit, respectively. Drug-induced neutralizing antibodies, as well as drug bioavailability in patients treated with adalimumab, were examined by ELISA.Results:Drug-induced neutralizing antibodies to adalimumab were detected in 11.57% of patients at 6 month, in 17.64% of patients at 12 month, and 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not detected at 6 months, at 7.77% at 12 months, at 9.63% of patients at 24 months. Of the adalimumab patients who were having drug-induced antibodies, 92.59% had low drug bioavailability, while the remaining 7.41% of patients showed normal drug bioavailability despite the presence of drug-induced neutralizing antibodies. In terms of worsening of the disease activity, a positive correlation was found with the presence of drug antibodies - Pearson Correlation = 0.701, p = 0.001. Patients with poor clinical response and available drug antibodies receiving adalimumab were slightly more than those treated with etanercept at 12 and 24 months but the difference is non-significant-U = 0.527, p> 0.05 and U = 0.623, p> 0.05, respectively.Conclusion:Presence of drug-induced neutralizing antibodies in patients treated with adalimumab and etanercept has been associated with poor clinical response and worsening of the patient’s condition. Testing of drug-induced neutralizing antibodies as well as the drug bioavailability of the drug used can be used as reliable biomarkers in clinical rheumatology.References:[1]Benucci M., F.Li Gobbi, M. Meacii et al., “Antidrug antibodies against TNF-blocking agents: correlations between disese activity, hypersensitivity reactions, and different classes of immunoglobulins”, Biologics and Targets and Therapy, 2015: 9 7 -2.[2]Chen D., Y. Chen, W. Tsai et al., “ Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis”, Ann Rheum Dis. 2015 Mar; 74 (3).[3]Kalden J. and H. Schulze-Koops, “ Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment ”, Nature Reviews Rheumatology, 2017 volume 13, 707–718.[4]Wolf-Henning Boehnck, N. Brembilla, “ Immunogenicity of biological therapies: causes and consequences, ” Expert Review of Clinical Immunology, Vol 14, 2018, Issue 6, 513-523Disclosure of Interests:None declared

Download Full-text

AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2503 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1437.2-1438

Author(s):

T. Kvlividze ◽

V. Polyakov ◽

В. Zavodovsky ◽

Y. Polyakova ◽

L. Seewordova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Blood Serum ◽

Inflammatory Cytokines ◽

Inflammatory Markers ◽

Healthy People ◽

Healthy Individuals ◽

Markers Of Inflammation ◽

High Level ◽

Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

Download Full-text

Measurement of the serum leptin level could assist disease activity monitoring in rheumatoid arthritis

Rheumatology International ◽

10.1007/s00296-006-0253-x ◽

2006 ◽

Vol 27 (6) ◽

pp. 537-540 ◽

Cited By ~ 55

Author(s):

Sang-Won Lee ◽

Min-Chan Park ◽

Yong-Beom Park ◽

Soo-Kon Lee

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Monitoring ◽

Serum Leptin

Download Full-text

Evaluation of Serum Biomarkers Associated with Radiographic Progression in Methotrexate-naive Rheumatoid Arthritis Patients Treated with Methotrexate or Golimumab

The Journal of Rheumatology ◽

10.3899/jrheum.120889 ◽

2013 ◽

Vol 40 (5) ◽

pp. 590-598 ◽

Cited By ~ 5

Author(s):

Carrie Wagner ◽

Dion Chen ◽

Hongtao Fan ◽

Elizabeth C. Hsia ◽

Michael Mack ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Radiographic Progression ◽

Statistical Significance ◽

Tumor Necrosis Factor Inhibitor ◽

Cd40 Ligand ◽

Joint Space ◽

Protein Profiling ◽

Serum Samples ◽

Markers Of Inflammation ◽

Factor Inhibitor

Objective.To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX).Methods.Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05.Results.Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group.Conclusion.These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.

Download Full-text

IgG Glycosylation Changes and MBL2 Polymorphisms: Associations with Markers of Systemic Inflammation and Joint Destruction in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110584 ◽

2012 ◽

Vol 39 (3) ◽

pp. 463-469 ◽

Cited By ~ 24

Author(s):

LONE N. TROELSEN ◽

SØREN JACOBSEN ◽

JODIE L. ABRAHAMS ◽

LOUISE ROYLE ◽

PAULINE M. RUDD ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Inflammation ◽

Joint Destruction ◽

Serum Levels ◽

High Expression ◽

Markers Of Inflammation ◽

Spearman's Rho ◽

Spearman’S Rho ◽

Factor Α ◽

Igg Glycosylation

Objective.To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA).Methods.IgG N-glycan content was determined from serum in 118 patients with RA by high-throughput glycan analysis using normal-phase high-pressure liquid chromatography. MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined. Systemic inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Joint destruction was assessed by total Sharp score (TSS) and alloplastic surgery records.Results.IgG hypogalactosylation was significantly correlated to IL-6 (Spearman’s rho = 0.32, p < 0.001), CRP (Spearman’s rho = 0.31, p < 0.001), TSS (Spearman’s rho = 0.25, p = 0.01), and alloplastic replacement of joints (Spearman’s rho = 0.18, p = 0.05). In multivariate analysis including age, CRP, anticitrullinated protein antibodies (ACPA), and other confounders, IgG hypogalactosylation was significantly associated with TSS (p = 0.014) and alloplastic joint replacement (OR 76.5, p = 0.041) in patients homozygous for the high expression MBL2 genotype YA/YA, but not in carriers of lower expression genotypes.Conclusion.Decreased galactosylation of IgG correlated to markers of inflammation, i.e., IL-6 and CRP. Only in patients homozygous for high expression of the MBL2 genotype YA/YA was IgG hypogalactosylation associated with markers of joint destruction. Our results suggest that inflammation-associated decreased galactosylation of IgG combined with high expression MBL2 genotypes are involved in the pathophysiology of RA.

Download Full-text