Katarzyna Fischer

Serum IL-6 and IL-23 Levels and Their Correlation with Angiogenic Cytokines and Disease Activity in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome

Objectives. To assess serum interleukin-6 (IL-6) and interleukin-23 (IL-23) and their correlation with angiogenic cytokines and disease activity in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and SAPHO syndrome. Patients and Methods. We studied 152 spondyloarthritis (SpA) patients: 69 PsA, 61 AS, 22 SAPHO, and 29 controls. We recorded age, sex, disease duration, and treatment. We assessed BASDAI, VAS, and PASI scores. Serum IL-6, IL-23, VEGF, EGF, FGFb, and FGFa levels were determined using ELISA. We estimated ESR and CRP. Results. Serum IL-6 and IL-23 levels were higher in SpA than in control (P < 0.00001 and P = 0.0004, resp.). There was a positive correlation between serum IL-6 and CRP in AS (P = 0.000001), PsA (P = 0.000001), and SAPHO (P = 0.0003) patients. There was a positive correlation between serum IL-6 and ESR in AS (P = 0.000001), PsA (P = 0.002), and SAPHO (P = 0.02) patients. There was no correlation of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines in SpA. Conclusions. Serum IL-6 but not serum IL-23 correlated with ESR and CRP in SpA. No correlation was found of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines.

Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome

To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC.

Extra-Articular Symptoms in Constellation with Selected Serum Cytokines and Disease Activity in Spondyloarthritis

Objectives. In this study, we assessed the extra-articular symptoms in constellation with selected serum cytokines and disease activity in spondyloarthritis (SpA). Patients and Methods. We studied 287 SpA patients: 131 had AS, 110 had PsA, and 46 had SAPHO. We assessed extra-articular symptoms in all cases. In 191 SpA patients, we measured serum interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-23 (IL-23), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). Results. Patients with acute anterior uveitis (AAU) had higher VAS (P = 0.0008), BADSDAI (P = 0.0001), ASDAS-ESR (P = 0.04), CRP (P = 0.006), IL-6 (P = 0.02), and IL-18 (P = 0.03) levels. Patients with inflammatory bowel disease (IBD) had higher VAS (P = 0.03), CRP (P = 0.0009), and IL-6 (P = 0.0003) levels. Patients with skin psoriasis had lower VAS (P = 0.001) and BASDAI (P = 0.00007) levels. Patients with psoriatic onycholysis had lower VAS (P = 0.006), BASDAI (P = 0.00001), and CRP (P = 0.02) and higher IL-23 (P = 0.04) levels. Patients with PPP had lower BASDAI (P = 0.04) and higher ET-1 (P = 0.001) levels. Conclusions. SpA patients with increased serum IL-18 and decreased serum ET-1 had an increased risk of extra-articular symptoms. In SpA patients, increased disease activity was associated with an increased risk of AAU and IBD and a decreased risk of skin psoriasis, psoriatic onycholysis, and PPP.

Serum Interleukin-23 in Polish Patients with Systemic Lupus Erythematosus: Association with Lupus Nephritis, Obesity, and Peripheral Vascular Disease

Objectives To analyze the correlation between the serum concentration of interleukin- (IL-) 23 and atherosclerotic changes, traditional atherosclerotic risk factors, the autoantibody profile, and involvement of selected organs in systemic lupus erythematosus (SLE) patients. Patients and Methods We studied 94 SLE patients and 27 controls. We analyzed the IL-23 serum concentration, autoantibodies, carotid intima-media thickness and atherosclerotic plaque, the ankle-brachial index, atherosclerotic risk factors, and organ manifestations. Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p = 0.0015). On the basis of multivariate stepwise analysis, we revealed that high levels of IL-23 were associated with atherosclerotic plaque in common femoral arteries (OR = 12.67; 95% CI: 1.41–113.84), lupus nephritis (OR = 3.69; 95% CI: 1.16–12.22), and obesity (OR = 4.21; 95% CI: 1.40–12.67). Autoantibodies related to IL-23 were anti-phosphatidylethanolamine antibodies (OR = 11.06; 95% CI: 1.24–98.65) and anti-SS-B/La antibodies (OR = 15.43; 95% CI: 1.73–137.25). Conclusions IL-23 may be involved in lupus nephritis pathogenesis. Through its association with obesity and selected antiphospholipid antibodies, IL-23 might promote a hypercoagulable state contributing to atherothrombosis development in SLE patients.

Arteriosclerosis or Vasculitis? Color Duplex Sonography in Giant Cell Arteritis

To the Editor: We followed with great interest the report by Czihal, et al 1 presenting new possibilities of objective, noninvasive diagnostic procedures that remain insufficient in giant cell arteritis (GCA). We would like to share our clinical experiences with arteritic changes in patients with GCA. Sonographic presentations of vasculitis may be mistaken for arteriosclerosis, especially in elderly patients who typically have GCA. That was the case in a patient with mild systemic manifestations and insidious disease onset. A 64-year-old woman presented with carotidynia — a rare manifestation of GCA. Color duplex sonography (CDS) revealed hypoechoic, homogenous, circumferential but not symmetrical bilateral wall thickening involving carotid and internal carotid arteries up to 15 mm from the carotid … Address correspondence to Dr. Milchert; E-mail: marcmilc{at}hotmail.com

Serum interleukin-23 protects, whereas methotrexate treatment stimulates selected components of the metabolic syndrome in patients with SAPHO syndrome

Introduction The aim of the study was to evaluate the impact of disease activity, selected serum cytokines, and therapy on metabolic syndrome (MetS) components in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Material and methods We studied 46 SAPHO patients (40 women, 6 men). We recorded age, sex, disease duration, arthritis localization, type of skin changes, bone scintigraphy results, comorbidities, BASDAI, VAS, and treatment. We measured erythrocyte sedimentation rate, C-reactive protein, lipid profile, serum IL-6, IL-18, IL-23, endothelin-1, vascular endothelial growth factor, and epidermal growth factor (EGF). Results 97.8% of patients had sternoclavicular joint arthritis, 91.3% of patients palmoplantar pustulosis. In 65.2% of SAPHO patients skin changes and arthritis started simultaneously. Apart from non-steroidal anti-inflammatory drugs, patients were treated with methotrexate (41.3%), sulfasalazine (41.3%), and antibiotics (39.1%). 19.5% of patients met MetS criteria. Serum IL-23 correlated positively with total cholesterol (TC; p = 0.02) and high-density lipoprotein cholesterol (HDL-C) (p = 0.01) in the SAPHO group. There was a negative correlation between HDL-C and BASDAI (p = 0.02). Patients treated with methotrexate had higher triglyceride (p = 0.01) and low-density lipoprotein cholesterol (LDL-C) (p = 0.01) levels. There was a negative correlation between TC and EGF (p = 0.03). Increased prevalence of autoimmune diseases and depression was observed in SAPHO patients. Conclusions Serum IL-23 protects, whereas methotrexate treatment stimulates selected components of the MetS in patients with SAPHO syndrome.

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

BACKGROUND Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction. OBJECTIVES The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications. MATERIAL AND METHODS The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations. RESULTS All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US. CONCLUSIONS Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

03.03 Serum interleukin 23 in polish patients with systemic lupus erythematosus – association with obesity and peripheral vascular disease

Background Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). The aim of this study was to evaluate association between serum levels of IL-23 and vascular involvement in SLE patients. Materials and methods Study was performed in 94 SLE patients (82 women and 12 men) aged 19–73 years and in 27 age and gender matched controls. Serum IL-23 was measured with ELISA method using R and D Systems tests. Carotid intima-media thickness and the presence of atherosclerotic plaques in carotid and lower extremities arteries were analysed with B-mode ultrasound. Ankle-brachial and high resistance indexes were measured with Doppler ultrasonography. We took into account classical cardiovascular risk factors (hypertension, dyslipidemia, hyperglycemia, overweight/obesity, smoking, oral contraceptives, positive family history of cardiovascular disease), selected clinical manifestations (cardiovascular, cerebrovascular, lupus nephritis, Raynaud’s phenomenon, livedo reticularis, vasculitis, other thromboembolic complications), profile of autoantibodies (antinuclear, antiphospholipid, anti-neutrophil cytoplasmic, anti-endothelial cell). Statistical analysis was performed with: chi 2Yates, chi 2Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0.0005). Patients with high levels of IL-23 more frequently developed atherosclerosis showed as the presence of plaques in right common femoral artery (OR=10.1; 95% CI:1.2–85.1) and lupus nephritis (OR=3.2; 95% CI:1.1–9.6). Among classical atherosclerotic risk factors only obesity was significantly associated with IL-23 (OR=3.8; 95% CI:1.2–12.3). Immunological characteristics significantly related to IL-23 were anti-phosphatidylethanolamine antibodies (OR=12.7; 95% CI:1.5–108.1) and anti-SS-B antibodies (OR=11.8; 95% CI:1.5–94.8). Association with anti-cardiolipin and anti-prothrombin antibodies was on the border of statistical significance (OR=2.3; 95% CI:0.9–5.7 and OR=8.4; 95% CI:1.0–71.1 respectively). Conclusions IL-23 may be involved in lupus nephritis pathogenesis. 2. IL-23 through its significant association with obesity and antiphospholipid antibodies may promote hypercoagulable state contributing to atherothrombosis development in SLE patients.

A5.07 The role of immunologic and inflammatory factors in the risk of microvascular and macrovascular impairment development in systemic lupus erythematosus – preliminary data

Background and objectives Vascular disorders are a well recognised clinical problem in systemic lupus erythematosus (SLE). This preliminary study was designed to evaluate the association between cerebral circulation changes, carotid arteries involvement as well as nailfold capillaroscopy (NC) abnormalities and immunologic/inflammatory markers, classical atherosclerosis risk factors and organ involvement in SLEpatients. Materials and methods The study was performed in 30 SLE patients. Bilateral transcranial doppler (TCD) monitoring over the middle cerebral arteries according to the criteria of the International Consensus Group on Microembolus Detection was performed using two 2-MHz probes of the pulsed Doppler system MultiDop-T Digital (DWL Compumedics). MRI scans of the brain were carried out using a 1.5-T scanner GE Discovery 450 (GE Healthcare). Detection of carotid stenosis was performed using 3D contrast-enhanced MR angiography. Carotid intima-media thickness (cIMT) was measured with B-mode ultrasound. NC was done using Zeiss device. More than 100 variables were taken into account including cytokines, inflammatory markers, autoantibodies, classical risk factors for atherosclerosis and selected organ manifestations. Statistical analysis was performed with chi2 Yates, chi2 Pearson, rank Spearman correlations tests and logistic regression analysis. Results Factors which significantly correlated with analysed vascular changes including microemboli in TCD, ischaemic changes in MRI and NC abnormalities, were thrombocytopenia (r = 0.47, p = 0.01), C-reactive protein (CRP) (r = 0.51, p = 0.0039) and antiphospholipid antibodies (aPLs) (r = 0.55, p = 0.0015). There was significant association between vascular endothelial growth factor (VEGF) and IL-6 and high cIMT (r = 0.36, p = 0.0492, r = 0.41, p = 0.0239, respectively) as well as NC abnormalities, especially megacapillaries presence (r = 0.38, p = 0.0415, r = 0.42, p = 0.0226, respectively). Additionally, patients with changes in NC significantly more frequently were dyslipidemic (r = 0.56, p = 0.0015), hypertensive (r = 0.41, p = 0.0252) and unveiled high titers of anti-dsDNA (r = 0.37, p = 0.0492) and cardiac involvement (r = 0.38, p = 0.0441). There was also important positive correlation between cIMT and NC abnormalities (r = 0.40, p = 0.0300) as well as microemboli in TCD (r = 0.44, p = 0.0211). Finally, microemboli in TCD were associated with MRI ischaemic changes (r = 0.45, p = 0.0177). Conclusions NC and cIMT provide the optimal protocol to screen SLE patients for cardiovascular risk. CRP, VEGF, IL-6, aPLs and anti-dsDNA seem to be crucial pathogenic factors in micro- and macrovascular impairment development in SLE. Patients with higher cIMT and aPLs should undergo TCD for cerebrovascular risk assessment.

A6.25 Serum concentrations of vascular endothelial growth factor in systemic lupus erythematosus – association with autoantibody profile and cardiovascular involvement

Background and objectives Angiogenesis plays a significant role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis as well as vasculogenesis. The study was designed to evaluate the association between VEGF concentrations and immunological parameters, inflammatory markers, classical atherosclerosis risk factors and vascular disorders in SLE patients. Materials and methods The study was performed in 83 patients with SLE and 20 age and gender matched controls. The concentrations of VEGF was determined with ELISA method using R&D Systems tests. The presence of inflammatory markers (ESR, CRP and fibrinogen) and selected autoantibodies - anti-endothelial (AECA), anti-nuclear, anti-phospholipid (aPL) and anti-neutrophil cytoplasmic was evaluated. Classical risk factors for atherosclerosis as well as selected organ manifestations (cardiovascular and central nervous system, lupus nephritis, thromboembolic disorders and vasculitis) were taken into account. Carotid intima-media thickness and atherosclerotic plaques were measured with B-mode ultrasound method. Statistical analysis was performed with chi2Yates, chi2Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results VEGF levels did not differ significantly between SLE patients and the controls (p > 0.1). The cut-off value of VEGF concentrations was established at 382.4 pg/ml (75- percentile). VEGF levels > 382.4 pg/ml were significantly associated with the elongation of activated partial thromboplastin time (OR = 22.8; 95% CI: 2.3–230.6) and the presence of aPL: anti-prothrombin (aPT) IgA class (OR = 10.7; 95% CI: 2.1–53.4), anti- β2-GPI IgA class (OR = 3.5; 95% CI: 1.1–10.8) and anti-oxidised low density lipoprotein antibodies (OR = 4.8; 95% CI: 1.0–22.8). Myocardial relaxation disorders were significantly more frequent in patients with high concentration of VEGF (OR = 8.0; 95% CI: 1.6–39.5). The low concentration of VEGF significantly decreased the risk of the existence of selected autoantibodies: aPT IgA (OR = 0.18; 95% CI: 0.0–0.72), aβ2-GPI IgA (OR = 0.17; 95% CI: 0.04–0.71), anti-double stranded DNA (OR = 0.31; 95% CI: 0,11–0.91) and AECA (OR = 0.30; 95% CI: 0,11–0.85). Furthermore, they were associated with reduction of the risk of atherosclerotic lesions in iliac arteries (OR = 0.24; 95% CI: 0.0–0.99) and vasculitis development (OR = 0.17; 95% CI = 0.03–0.91). Conclusions 1. High VEGF levels may increase the prothrombotic risk in SLE patients because of the significant association with the presence of antiphospholipid antibodies. 2. The lower concentrations of VEGF significantly decrease the risk of persistence of selected autoantibodies and atherosclerotic lesions as well as vasculitis development in SLE patients.