Immunometabolic biomarkers of inflammation in Behçet's disease: relationship with epidemiological profile, disease activity and therapeutic regimens

Abstract

Behcet's disease (BD) is a systemic inflammatory disease with a still unclear pathogenesis. Although several inflammatory molecules have been studied, current biomarkers are largely insensitive in BD and unable to predict disease progression and response to treatment. Our primary aim was to explore serum levels of soluble CD40 L (sCD40L), soluble intracellular adhesion molecule (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), leptin, resistin, osteoprotegerin (OPG), soluble type 1 tumour necrosis factor receptor (sTNFR), interleukin (IL)-6 and serum amyloid A (SAA) serum concentration in a cohort of 27 BD patients. The secondary aim was to evaluate potential correlations between the putative circulating biomarkers, demographic profile of patients, the status of disease activity, the specific organ involvement at the time of sample collection and different therapeutic regimens. Serum concentrations of sTNFR (P = 0·008), leptin (P = 0·0011), sCD40L (P < 0·0001) and IL-6 (P = 0·0154) were significantly higher in BD patients than in HC, while no difference was found in MCP-1, MPO and resistin serum levels. Moreover, we observed significantly higher sTNFR serum concentrations in BD patients presenting inactive disease than HC (P = 0·0108). A correlation between sTNFR and age was also found, with higher levels in patients over 40 years than HC (P = 0·0329). Although further research is warranted to elucidate the role of circulating biomarkers, some of that may contribute to the understanding of the physiopathology processes underlying BD activity and damage as well as to provide useful tools for prognostic purposes and a personalized treatment approach.

Keywords: Behçet's disease; cytokines; leptin; metabolism; sTNFR.

Figure 1

Erythrocyte sedimentation rate (ESR) values in Behçet's disease (BD) patients with active (n = 29) and inactive (n =19) disease. Comparison was performed by the Mann–Whitney U‐test; n = number of samples.

Figure 2

Serum levels of adipocytokines in Behçet's disease (BD) patients and healthy controls (HC). Serum levels of soluble type 1 tumour necrosis factor receptor (sTNFR), leptin, soluble CD40L (sCD40L) and interleukin (IL)‐6 were detected in BD patients (n = 57) and HC (n = 33) samples. Pairwise comparisons were performed by the Mann–Whitney U‐test; n = number of samples.

Figure 3

Adipocytokine serum levels according to disease activity. Serum levels of soluble type 1 tumour necrosis factor receptor (sTNFR), soluble CD40L (sCD40L) and leptin in Behçet's disease (BD) patients with active (n = 29) or inactive disease (n = 24) compared with healthy controls (HC) (n = 33). Comparisons of baseline data among the three groups were performed using the Kruskal–Wallis test for sTNFR and leptin serum levels and using analysis of variance (anova) for sCD40L circulating levels. Pairwise comparisons were performed by the Mann–Whitney U‐test in all cases; n = number of samples.

Figure 4

Serum levels of circulating adipocytokines according to age, disease duration, gender, genotype and body mass index (BMI) in Behçet's disease (BD) patients. Serum levels of soluble type 1 tumour necrosis factor receptor (sTNFR), leptin, soluble intracellular adhesion molecule 1 (sICAM‐1), soluble CD40L (sCD40L) and myeloperoxidase (MPO) in BD patients in according to the age (a,b), disease duration (c), gender (d–f), human leucocyte antigen (HLA)‐B51 (g–i) and BMI (j–l) at the time of serum collection. Comparisons of data among the three groups were performed by means of using analysis of variance (anova) or Kruskal–Wallis test according to the type of distribution; pairwise comparisons were performed by the Mann–Whitney U‐test; n = number of samples.

Figure 5

Immunometabolic profile of Behçet's disease (BD) patients according to different drug treatments. Serum levels of soluble type 1 tumour necrosis factor receptor (sTNFR), leptin and soluble CD40L (sCD40L) in BD patients in according to different treatment approaches. Histograms (a–c) refer to patients treated with disease‐modifying anti‐rheumatic drugs (DMARDs) (n = 15) or biological agents (n = 24) compared with healthy controls (HC) (n = 18) and patients with no therapy (n = 18); histograms (d,e) are related to BD patients administered with high (n = 41) and low corticosteroid (CTS) dosages (n = 12). Comparisons of data among multiple groups were performed using analysis of variance (anova) or Kruskal–Wallis test according to the type of distribution; pairwise comparisons were performed using the Mann–Whitney U‐test; n = number of samples.