Assessment of serum interleukin-20 level in rheumatoid arthritis patients: Relation to disease activity and ultrasound measures

Aim of the workTo investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings.Patients and methods45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score (DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay.ResultsMean age of patients was 34.5 ± 11 years; 39 females and 6 males and disease duration 15.8 ± 8.3 years. Their mean DAS-28 was 4.1 ± 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1–58.5 ng/l) than in controls 13.1; 11–15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL- 20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001).ConclusionPatients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA.     

Galectin-3 and interleukin-7 as potential serologic markers in rheumatoid arthritis patients

Aim of the workTo assess the level of serum galectin-3 and interleukin-7 (Il-7) in rheumatoid arthritis (RA) patients and to study their association with disease activity as well as other disease parameters.Patients and methodsSerum samples from 66 RA patients and 20 matched controls were tested for galectin-3 and IL-7 using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using disease activity score (DAS28).ResultsThe mean age of the patients was 46.6 ± 12.02 years, mean disease duration was 7.5 ± 7.6 years and they were 61 females and 5 males. The mean DAS28 of the patients was 4.72 ± 1.77. Serum galectin-3 and IL-7 were higher in RA patients (7.7 ± 5.7 ng/ml and 9.03 ± 5.97 pg/ml) than the control (1.5 ± 0.8 ng/ml and 1.6 ± 1.1 pg/ml) (p < 0.001). Serum galectin-3 and IL-7 significantly correlated with age (r = 0.27, p = 0.03 and r = 25, p = 0.04), DAS28 (r = 0.64, p < 0.001 and r = 39, p = 0.001), as well as to each other (r = 0.48, p < 0.001). Serum galectin-3 significantly correlated with ESR (r = 0.29, p = 0.018) and significantly higher in those with fever (p = 0.017). At a cutoff of 2.94 ng/ml, serum galectin-3 showed 84.8% sensitivity and 100% specificity (p < 0.001) and at 2.71 pg/ml, serum IL7 showed a sensitivity of 92.4% and a specificity of 95% (p < 0.001) to diagnose RA.ConclusionSerum galectin-3 and IL-7 were higher in patients than in controls and were increased with high disease activity making them promising biomarkers for RA. Both of them showed high diagnostic power for RA. This may provide further understanding of RA pathogenesis and suggest new therapeutic interventions.     

Serum interleukin-6 in primary fibromyalgia syndrome patients: Impact on disease burden,severity, quality of life and sleep

Aim of the workTo assess serum interleukin-6 (IL-6) level in primary fibromyalgia syndrome (FMS) patients and to study its relation to disease burden parametersPatients and methodsForty primary FMS patients and 40 age and sex matched controls were studied. Patients answered multiple questionnaires. Fatigue was assessed by multidimensional fatigue inventory (MFI-20), pain severity by visual analogue scale (VAS-pain) and sleep quality by sleep quality numerical rating scale (NRS). The 36-Item Short Form (SF-36) was used to assess quality of life and fibromyalgia Impact Questionnaire (FIQ) was used to evaluate patient status, progress and outcomes.ResultsThe patients mean age was 36.5 ± 7.1 years and disease duration 5.3 ± 2.95 years and they were 38 females and 2 males. The mean serum IL-6 level was significantly higher in patients (134.9 ± 67.3 pg/ml) than control (41.1 ± 8.5 pg/ml)(p = 0.001). The mean VAS-pain was 6.2 ± 1.3 (4–8), FIQ was 58 ± 6.1 (50–70), SF-36 47 ± 10.2 (30–60), MFI20 was 76.5 ± 10.6 (60–95) and sleep quality NRS was 6.9 ± 1.2 (5–9). The values of the studied parameters and scores were significantly different from the control 1.4 ± 0.5; 14.4 ± 6.5; 93.9 ± 3.5 10 ± 5.2 and 0.9 ± 0.8 respectively; p = 0.001 for all). There was a significant correlation between serum IL-6 levels and VAS-pain (r = 0.72, p = 0.001), FIQ (r = 0.58, p = 0.001), SF-36 (r = 0.78, p = 0.001), MFI-20 (r = 0.74, p = 0.001) and sleep NRS (r = 0.78,p = 0.001). On regression, IL-6 level had a greater impact on sleep NRS (p = 0.001), SF-36 (p = 0.005) and MFI20 (p = 0.01).ConclusionsSerum IL-6 level is high in primary FMS patients. Also, serum IL-6 is significantly related to the parameters of fatigue, functional status, sleep quality and pain.     

Interleukin-23 serum level in systemic lupus erythematosus patients: Relation to disease activity and different disease parameters

Aim of the workTo assess serum level of interleukin 23 (IL-23) in systemic lupus erythematosus (SLE) patients and to evaluate its association with disease parameters and activity.Patients and methodsThe study involved 40 SLE patients and 40 controls. The SLE disease activity index (SLEDAI) and damage index (SDI) were assessed. Serum level of IL-23 was measured by enzyme linked immunosorbant assay (ELISA).ResultsPatients were 38 females and 2 males (F:M 19:1),with a mean age of 31.3 ± 7.5 years (17–50 years) and disease duration 4.8 ± 2.9 years (1–13 years). Their mean SLEDAI was 14.3 ± 6.8 (3–32) and SDI 0.4 ± 0.5 (0–2). 85% of patients had photosensitivity, alopecia in 60%, malar rash in 57.5%, oral ulcers 52.5%, arthralgia/arthritis 47.5%, serositis and lupus nephritis in 27.5%, discoid rash in 22.5% and neuropsychiatric in 2.5%. Mean serum level of IL-23 was significantly elevated in patients (107.9 ± 17.3 ng/L; 72.7–165.5 ng/mL) compared to controls (91.6 ± 19.1 ng/L; 57.6–140.3 ng/mL; p < 0.001). IL-23 was significantly elevated in patients with oral ulcers (p = 0.03), arthritis (p < 0.001), lupus nephritis (p = 0.01), alopecia (p = 0.02) and positive anti-dsDNA (p < 0.001). IL-23 significantly correlated with SLEDAI (r = 0.89, p < 0.001), complement C3 (r = -0.55, p < 0.001) and C4 (r = -0.5, p = 0.001). IL-23 could significantly predict SLE at a cut-off 93.1 ng/L (sensitivity 80% and specificity 55%).ConclusionIL-23 may be involved in the pathogenesis of SLE; especially in renal, mucocutaneous and musculoskeletal manifestations and it can be used as a disease activity biomarker. These findings support the possibility of its use as a therapeutic target in SLE.     

Serum level of galectin-9 in systemic lupus erythematosus patients with lupus nephritis: Relation to clinical characteristics and disease activity

Aim of the workTo assess galectin-9 (Gal-9) level in the serum of systemic lupus erythematosus (SLE) patients with and without renal involvement and clarify its relation with disease activity.Patients and methods50 SLE patients; 25 with lupus nephritis (LN) and 25 without as well as 25 controls were studied. Systemic Lupus International Collaborating Clinics (SLICC) renal activity score and SLE disease activity index 2000 (SLEDAI-2 K) were determined. Serum Gal-9 was measured in all participants.ResultsGal-9 level was significantly elevated in SLE patients with (16.7; 11.6–33.7 ng/ml) and without (15.9; 11.8–25 ng/ml) compared to controls (3.9; 2.8–5.4 ng/ml) (p < 0.001) but was comparable between the patients groups (p = 0.83). In LN patients, serum Gal-9 and SLICC renal activity score significantly correlated (r = 0.48, p = 0.016). Serum Gal-9 significantly correlated with SLEDAI-2 K in patients with (r = 0.71, p < 0.001) and without (r = 0.95, p < 0.001) LN, with anti-double stranded deoxyribonucleic acid (anti-ds-DNA) titers (with r = 0.57, p < 0.001 and without r = 0.79, p < 0.001) and inversely with C3 (with r = -0.44, p = 0.027 and without r = -0.63, p < 0.001) and C4 (with r = -0.47, p = 0.018 and without r = -0.43, p = 0.03). Gal-9 had an area under the curve (AUC) of 0.96 to distinguish SLE cases from control. However, AUC between LN group and non-nephritic SLE was 0.48. On regression, SLEDAI-2 K was the only significant factor associated with serum Gal-9 (p < 0.001).ConclusionIn SLE patients, significantly raised Gal-9 levels and relation with disease activity were detected indicating its clinical relevance as biomarker of disease activity and its potential value in the disease diagnosis. Its value in discriminating LN from non-nephritic SLE is limited.     

High protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors

Background and aimsHigh Protein diets may be associated with endocrine responses that favor improved metabolic outcomes. We studied the response to High Protein (HP) versus High Carbohydrate (HC) Diets in terms of incretin hormones GLP-1 and GIP, the hunger hormone ghrelin and BNP, which is associated with cardiac function. We hypothesized that HP diets induce more pronounced release of glucose lowering hormones, suppress hunger and improve cardiac function.Methods and results24 obese women and men with prediabetes were recruited and randomized to either a High Protein (HP) (n = 12) or High Carbohydrate (HC) (n = 12) diet for 6 months with all food provided. OGTT and MTT were performed and GLP-1, GIP, Ghrelin, BNP, insulin and glucose were measured at baseline and 6 months on the respective diets.Our studies showed that subjects on the HP diet had 100% remission of prediabetes compared to only 33% on the HC diet with similar weight loss.HP diet subjects had a greater increase in (1) OGTT GLP-1 AUC(p = 0.001) and MTT GLP-1 AUC(p = 0.001), (2) OGTT GIP AUC(p = 0.005) and MTT GIP AUC(p = 0.005), and a greater decrease in OGTT ghrelin AUC(p = 0.005) and MTT ghrelin AUC(p = 0.001) and BNP(p = 0.001) compared to the HC diet at 6 months.ConclusionsThis study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for improved insulin sensitivity and β cell function compared to the HC diet. HP ghrelin results demonstrate the HP diet can reduce hunger more effectively than the HC diet. BNP and other CVRF, metabolic parameters and oxidative stress are significantly improved compared to the HC diet.Clinicaltrials.gov identifierNCT01642849.     

Serum beta2-microglobulin level in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo assess the level of β2-microglubulin (β2M) in systemic lupus erythematosus (SLE) patients and its association with disease activity and other disease parameters.Patients and methods40 SLE patients and 22 matched controls were studied. Serum β2M was assessed using enzyme-linked immunosorbent assay (ELISA). SLE Disease Activity Index (SLEDAI) and the damage index were assessed.ResultsThe patients were 36 females and 4 males (F:M 9:1) with a mean age of 28.5 ± 7.9 years and disease duration of 6.7 ± 3.3 years. The SLEDAI was 9.3 ± 5.2 and the damage index 1.83 ± 1.84. The mean level of serum β2M was significantly higher in SLE patients (6.42 ± 2.46 mg/L) than control (2.47 ± 0.4 mg/L) (p < 0.01).The serum level of β2M was significantly higher in patients with nephritis (n = 22) (7.45 ± 2.47 mg/L) compared to those without (n = 18) (5.17 ± 1.82 mg/L)(p = 0.002), And it was similar in those with and without arthritis (7.24 ± 2.3 mg/L vs 5.88 ± 2.4 mg/L (p0.07).The β2M significantly correlated with disease activity (r = 0.86, p 0.001), serum creatinine (r = 0.52, p > 0.001), urea (r = 0.63, p < 0.001), 24 h urinary protein (r = 0.56, p < 0.001), hematuria (r = 0.4, p < 0.01) and pyuria (r = 0.41; p < 0.01), ESR (r = 0.48; p < 0.01) and inversely with hemoglobin level (r = ?0.34; p = 0.03). No significant correlation was found with C-reactive protein or with disease damage. Serum (β2M) significantly predicted nephritis and disease activity (sensitivity 63.6 %, specificity 77.8 %; p < 0.001 and 95 %CI: 0.25–0.41; p < 0.001 respectively).ConclusionSerum β2M is significantly associated with disease activity and lupus nephritis, suggesting that serum β2M may serve as a potential biomarker to monitor the disease activity and predicting lupus nephritis. However its association to disease severity needs further longitudinal studies.     

Optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis

Aim of the workTo report optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis (JIA) patients and to study the relation to disease activity.Patients and methodsThe study included 20 JIA patients (38 eyes) who underwent ophthalmologic and rheumatologic examination plus OCT/OCTA. Juvenile arthritis disease activity score (JADAS27) was assessed, and patients were divided into those with no/low activity (group 1; n = 13) and moderate/severe activity (group 2; n = 7). OCTA findings were compared with 11 control (11 eyes).ResultsThe study included 20 JIA-U patients (38 eyes) with a mean age of 10.7 ± 2.6 years and disease duration of 72.5 ± 34.7 months and they were 9/20 (45 %) females. 13(65 %) patients had no/mild activity (group 1, 25 eyes) while 7(35 %) had moderate to severe activity (group 2, 13 eyes). The mean foveal superficial and deep capillary plexuses (SCP/DCP) vascular density (VD) were significantly lower in patients with moderate/severe activity (3x3 scan: p = 0.001 and p < 0.001; 6x6 scan p = 0.008 and p = 0.001 respectively). The foveal avascular zone (FAZ) 3x3 and 6x6 scans were significantly increased and the central macular thickness (CMT) decreased in patients with moderate/severe disease activity (p < 0.001, p = 0.001, and p = 0.001). Fovea SCP VD in 6x6 and 3x3 scans were significantly different between JIA subtypes (p = 0.01 and p = 0.03, respectively), with less VD in oligoarticular type. FAZ, CMT and DCP-VD significantly correlated with visual analogue scale (r = 0.58, p < 0.001; r = ?0.5, p = 0.01; r = ?0.58, p < 0.001, respectively).ConclusionsNon-invasive OCTA-derived vascular parameters of the macula could be potential biomarkers for evaluating the severity of the systemic disease activity in JIA patients.     

Serum irisin level in rheumatoid arthritis patients: Relationship to disease activity,subclinical atherosclerosis,and cardiovascular risk factors

Aim of the workTo assess serum irisin level in rheumatoid arthritis (RA) patients, determine the relationship between irisin levels, disease activity and cardiovascular (CV) risk factors, and to evaluate its performance in predicting subclinical atherosclerosis and disease activity.Patients and methods60 RA patients and 30 controls were recruited for serological enzyme linked immunosorbant assay (ELISA) testing of irisin levels. Disease activity score (DAS28), health assessment questionnaire disability index (HAD-DI) and American college of rheumatology classification of functional status were assessed. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), glycated hemoglobin (HbA1c), insulin and lipid profile were measured. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Carotid intimal medial thickness (C-IMT) was measured and echocardiography performed.ResultsSerum irisin levels were significantly lower in patients (9.8 ± 10.6 ng/ml) vs. controls (20.5 ± 13.8 ng; p < 0.001). Irisin levels inversely correlated significantly with C-IMT, body mass index (BMI), HOMA-IR, disease activity and disability. Patients with CV involvement showed significantly lower serum irisin level, increased disease activity and disability. Classifying patients based on cut-off values of DAS28 into low, moderate, and high disease activity, a significant difference in irisin levels was found, being lowest among highly active patients. Irisin performed as an excellent independent indicator of subclinical atherosclerosis (p < 0.001) and high disease activity (p < 0.001) in RA patients.ConclusionIn RA, decreased irisin were significantly associated with increased CV risk and performed better than traditional yardsticks in identifying disease activity. It may act as an independent indicator of subclinical atherosclerosis within RA patients.     

Serum,synovial and mRNA expression of interleukin-33 in juvenile idiopathic arthritis patients: Potential role as a marker of disease activity and relation to musculoskeletal ultrasound

Aim of the workTo measure interleukin-33 (IL-33) serum and synovial fluid (SF) levels as well as its relative expression in peripheral blood mononuclear cells (PBMC) of juvenile idiopathic arthritis (JIA) patients and to study their relation to clinical, laboratory and musculoskeletal ultrasound characteristics, disease activity and functional status.Patients and methodsThe study included 60 JIA patients and 60 healthy controls and SF levels were measured in 20. Juvenile arthritis disease activity score (JADAS27) and Juvenile Arthritis Multidimensional Assessment Report (JAMAR) were assessed; Ten-joint grey scale (GS) and power Doppler (PD) MSUS score was performed. Rheumatoid factor (RF) titer and C-reactive protein (CRP) levels were measured.ResultsIn JIA patients, serum IL-33 levels (median 12.6; 7.4–23.8 ng/l) and its relative mRNA expression (median 3.3; 2.5–3.7) were significantly higher than their levels in the controls (median 1.7; 0.8–2.4 ng/l and median 1 ng/ml; p < 0.001). Polyarticular subtype (n = 20) had higher IL-33 serum levels compared to oligoarticular (n = 28, p < 0.001) and systemic-onset (n = 12, p = 0.006) subtypes. In JIA patients, the serum and SF levels of IL-33 significantly correlated with JADAS27 (p < 0.001 and 0.002 respectively), CRP (p < 0.001 and 0.007 respectively), GS (p < 0.001 and 0.001 respectively) and PD (p < 0.001 and 0.005 respectively). Serum IL-33 correlated with RF (p = 0.039) while, SF IL-33 correlated with physical function (p = 0.02).ConclusionsJIA patients have significantly elevated IL-33 serum concentrations and mRNA expression that considerably correlated with different inflammatory parameters, RF and physical function suggesting that it could be a valuable marker of JIA disease activity and implies a possible prognostic role.     

Cutaneous immunohistochemical expression of interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis patients: Relation to musculoskeletal ultrasound findings

Aim of the workTo assess the immunohistochemical expression of cutaneous interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis (PsA) patients and study its relation to musculoskeletal ultrasound (MSUS) findings.Patients and methodsThe study was conducted on 40 patients: 20 with PsA and 20 with psoriasis only. The psoriasis area severity index (PASI) was estimated. Synovitis was assessed by Power Doppler ultrasound and enthesitis by Glasgow Ultrasound Enthesitis Scoring System (GUESS).ResultsThe mean age of PsA and psoriasis only patients (49.9 ± 11.6 and 44.9 ± 13 years) and gender (12 males and 8 females each) were comparable. IL-23R expression in the epidermal keratinocytes and dermal inflammatory cells of PsA patients scored 5 in 40% and 4 in 45% respectively while in psoriasis only the highest frequency of cases (40%) scored 2 in both. In psoriasis only, dermal and epidermal IL-23R were significantly associated to effusion (5 ± 0 vs 2.2 ± 0.7 and 4 ± 0 vs 1.5 ± 0.5, p < 0.001 respectively) and synovitis (5 ± 0 vs 2.4 ± 1 and 4 ± 0 vs 1.7 ± 0.8, p < 0.001 respectively) (p < 0.001) and both significantly correlated with erosions (r = 0.64, p = 0.002 and r = 0.64, p = 0.003) and GUESS (r = 0.68, p = 0.001 and r = 0.61, p = 0.005). Dermal IL-23R was significantly associated with the PASI score in PsA patients (r = 0.59, p = 0.01). On regression, IL-23R significantly predicted PsA (epidermal: p = 0.001 and dermal: p = 0.018).ConclusionIL-23R is highly expressed in psoriatic skin and strongly associated with psoriatic skin, joints and entheses findings. MSUS is valuable in the detection of subclinical arthritis. Cutaneous IL-23R expression may refer to early joint affection and with MSUS may allow early prediction and management.     

Krebs von den Lungen-6 (KL-6), soluble programmed cell death-1 (sPD-1) and its ligand-1(sPDL-1) in systemic sclerosis patients: Relation to disease parameters

Aim of the workThis study aimed to assess the levels of Krebs von den Lungen-6 (KL-6), soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1(sPDL-1) in systemic sclerosis (SSc) patients, and to evaluate their relation with disease parameters.Patients and methodsForty-six SSc patients (31 limited, 15 diffuse) and 43 matched controls were included. Serum levels of KL-6, sPD-1, and sPDL-1 were assessed by enzyme-linked immune-sorbent assay (ELISA).ResultsPatients mean age was 40.2 ± 12.2 years, disease duration 8.04 ± 6.02 years and females: male was 10.5:1. Levels of KL-6, sPD-1, and sPDL-1 were significantly higher in SSc patients compared to the controls 22.4(14.1–637.6) vs. 14.8(8.9–182.3) (p < 0.001), 3.1(1.8–64.2) vs. 1.2(0.68–14.4) (p < 0.001), and 2.8(1.5–84.4) vs. 1.4(0.92–36.4) (p < 0.001) respectively. KL-6 and sPD-1 levels were significantly lower in diffuse SSc subtype than the limited subtype 20.7(14.1–637.6) vs. 24.5(16.2–328.8) (p = 0.01), and 2.5(1.8–64.2) vs. 3.2(2.1–63.4) (p = 0.03) respectively. KL-6 was significantly decreased in SSc patients who developed pulmonary hypertension compared to those without 20.9(14.1–36.3) vs. 27.5(16.5–637.6) (p = 0.02), and in those who received cyclophosphamide 21(14.1–310.9 vs. 31.6(16.2–637.6) (p = 0.019). The three markers were significantly correlated. KL-6 levels with sPD-1 (r = 0.79, p < 0.001) and sPDL-1 (r = 0.79, p < 0.001) and between sPD-1 and sPDL-1 (r = 0.82, p < 0.001) respectively. Both sPD-1 and sPDL-1 significantly correlated with age (r = 0.29, p = 0.048 and r = 0.34, p = 0.021 respectively).ConclusionsKL-6, sPD-1, and sPDL-1 may be considered as potential biomarkers in the diagnosis and assessment of SSc patients. Significantly lower levels of KL-6 were detected in diffuse SSc patients, those with pulmonary hypertension, and patients who received cyclophosphamide.     

Serum interleukin-26 is a promising biomarker in systemic lupus erythematosus patients: Particular relation to disease activity and nephritis

Aim of the workTo investigate the clinical utility of serum interleukin-26 (IL-26) in patients with systemic lupus erythematosus (SLE).Patients and methodsThe study was carried out on 42 SLE patients and 42 matched controls. SLE disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) were assessed. Serum IL-26 was measured.ResultsThe mean age of patients was 28.8±11.4 years with 78.6% females. 76.2% of patients were active; 7.1% very-high grade, 45.2% high, 16.7% moderate and 31% mild. 42.9% of patients had nephritis. The mean SLEDAI-2K was 10.4±6.4 and SLICC-DI 1.19±1.15. IL26 level was significantly higher in patients (64±76.4 pg/ml) compared to control (8.7±2.6 pg/ml), in active cases (79.2±81.9 pg/ml) compared to those inactive (15.3±4.8 pg/ml) and in those with nephritis (n = 18) (113.4±92.2 pg/ml) compared to those without (n = 24) (23.1±7.6 pg/ml).IL-26 level was significantly higher among cases receiving both steroids and mycophenolate mofetil than those receiving steroids with azathioprine (p = 0.005). There was a significant negative correlation between IL26 and serum albumin, hemoglobin and complement 3 (C3) levels (p < 0.001, p < 0.001 and p = 0.006 respectively). There was also a significant correlation between IL26 and both SLEDAI-2K (r = 0.95, p < 0.001) and SLICC-DI (r = 0.68, p < 0.001). At cut off value 16.3 pg/ml, IL26 differentiated patients and control; sensitivity 90.5%, specificity 100% (F. 2) and at 20 pg/ml detects active from non-active; sensitivity and specificity 100%.ConclusionIL-26 is a promising biomarker of SLE with high sensitivity and specificity. There is a relation of IL-26 with disease activity, damage and nephritis.     

Evaluation of serum calprotectin level as a biomarker of disease activity in rheumatoid arthritis and osteoarthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) and osteoarthritis (OA) patients and to assess its association with disease activity, severity and functional status.Patients and methodsA total of 30 RA and30 OA patients and 30 controlswere included. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), Disease activity score (DAS28), health assessment questionnaire (HAQ) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. Western Ontario and McMaster Osteoarthritis index (WOMAC) and Kellgren-Lawrence (KL) grading scale were assessed in OA patients and serum CLP levels were measured.ResultsThe mean age of RA and OA patients was 48.6 ± 8.6 and 50.8 ± 9.3 years respectively andthe majority of studied groups were females. CLP was significantly higher in RA patients in comparison to OA patients and healthy control (2.70 ± 2.08 vs. 1.18 ± 0.35 vs 1.11 ± 0.24 μg/ml); p < 0.0001). Serum CLP correlated with swollen joint count (SJC) (r = 0.7, p < 0.0001), tender joint count (TJC) (r = 0.73, p < 0.0001), patient global assessment (PGA) (r = 0.51, p = 0.004), Physician global assessment (PhGA) (r = 0.58, p = 0.001), HAQ (r = 0.6,p < 0.0001), erythrocyte sedimentation rate (ESR) (r = 0.5, p = 0.005), DAS28 (r = 0.69, p < 0.0001), RARBIS (r = 0.66, p < 0.0001). At a cut-off value of 2.5 µg/ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.896; p < 0.0001) at a sensitivity of 83.3%, specificity of 88.9%, and accuracy of 86.7%.CLP was significant predictor for RA activity.ConclusionThe serum CLP levels were significantly high in RA patients compared to OA patients and controls and these high levels were associated with disease activity, severity, and functional status.     

Comparative effectiveness of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on noninvasive indices of hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus

Background and aimsNonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM.MethodsIn this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6–18 months) the addition of a DPP-4i (n = 152) or a GLP-1 RA (n = 37) in patients with T2DM.ResultsRegarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p = 0.001), but not in the DPP-4i group (p = 0.25); the difference for group1time interaction was significant (p = 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group1time interaction. Indices of fibrosis were not essentially changed within or between groups.ConclusionsNAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials.     

Collagen triple-helix repeat containing 1 (CTHRC1) protein in rheumatoid arthritis patients: Relation to disease clinical,radiographic and ultrasound scores

Aim of the workto study the relationship between collagen triple helix repeat containing 1 (CTHRC1) protein serum levels and disease activity, patients’ well-being, as well as ultrasonographic and radiological scores in patients with rheumatoid arthritis (RA).Patients and methodsThe work included 70 RA patients and 70 age and gender matched controls. The disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Modified Larsen's score was used to score the hands and feet digital radiographs and musculoskeletal ultrasound (MSUS) examination using ultrasound-7 score was carried out. Serum CTHRC1 levels were measured by ELISA.ResultsPatients were 62 females and 8 males (F: M 7.8:1), their mean age was 42.2 ± 17.7 years and median disease duration 15 years. The median CTHRC1 serum levels were significantly higher in patients (453 ng/dl; 158–688 ng/dl) than control (99 ng/dl; 67–179 ng/dl) (p < 0.001). CTHRC1 was significantly increased in those with high activity (p < 0.001).CTHRC1 levels significantly correlated with DAS28 (r = 0.87,p < 0.001), CRP (r = 0.43,p < 0.001) and total ultrasound-7 score (r = 0.27,p = 0.03). Only total US7 score (p = 0.003) and CTHRC1 (p < 0.001) were significant predictors of activity. Serum CTHRC1 could significantly differentiate between patients and controls at cut off 179 ng/ml; sensitivity 95.7 % and specificity 100 % (p < 0.001) and between patients active and in remission at cut off 324 ng/ml; sensitivity 92.2 % and specificity 94.7 % (p < 0.001).ConclusionsPatients with RA have significantly elevated serum levels of CTHRC1. In the process of structural bone ultrasonographic abnormalities as well as disease activity in RA patients, elevated CTHRC1 levels play a key role.     

Relationship between PCSK9 and endothelial function in patients with acute myocardial infarction

Background and aimsWhile the role of PCSK9 in lipid metabolism is well established, its link with endothelial function is less clear. The aim of the present study is to evaluate the relationship between PCSK9 and endothelial dysfunction in the setting of acute myocardial infarction.Methods and resultsTo this purpose, we analyzed the serum of 74 patients with ST-elevation myocardial infarction (STEMI) at the time of admission and after 5 days. Endothelial dysfunction was evaluated as rate of apoptosis (AR) of human umbilical vein endothelial cells incubated with patients’ serum. There was a good correlation between PCSK9 and the apoptosis rate values, both at baseline (r = 0.649) and 5-day (r = 0.648). In the 5 days after STEMI, PCSK9 increased significantly (242–327 ng/ml, p < 0.001), while AR did not (p = 0.491). Overall, 21 (28%) patients showed a reduction of PCSK9, and they had a significantly higher decrease of AR as compared to others (?13.87 vs 5.8%, p = 0.002). At the univariable analysis, the 5-day change of PCSK9 resulted to be the only variable associated with the 5-day change of the apoptosis rate (beta 0.217, 95%CI 0.091–0.344, p = 0.001).ConclusionThe variation of endothelial function and PCKS9 in the first days after an acute myocardial infarction are related. Further validation and research are necessary to confirm our findings.Clinical trialNCT02438085.     

Elevated serum levels of S100A1 and zinc α2-glycoprotein in patients with heart failure

Background and aimsHeart failure (HF) is a growing concern worldwide. S100A1 and zinc α2-glycoprotein (ZAG) play an important role in heart function. We examined serum levels of S100A1 and ZAG in HF patients and their association with anthropometric indices and body composition.Methods and resultsSixty-four patients with HF, mean age 56.2, 48 male and 16 females, with ejection fraction <30–35%, were recruited from Shahid Madani Heart Hospital in Tabriz, Iran, from April to October 2019. Two groups, cachexia (n = 32) and non-cachexia (n = 32), which were divided based on weight loss of at least 7.5% in the last six months, were compared with the control group (n = 26). S100A1 and ZAG serum levels were determined by ELISA.Serum median (min–max) levels of S100A1 and ZAG were significantly greater in HF patients [326 (184.8–635.2) and 150.4 (61.5–520.7)] than healthy controls [265.4 (43.6–658.8) and 119.8 (16.7–533)], both p = 0.001. S100A1 Serum levels in cachexia group was significantly higher than non-cachexia group [331 (245.6–469.6) vs. 318 (184.8–635.2), p = 0.03]. A strong positive association was observed between S100A1 and ZAG serum levels in patients (r = 0.70, p < 0.0001). Serum levels of these two proteins negatively and significantly associated with BMI (r = ?0.25, p = 0.044 and r = ?0.28, p = 0.024, respectively) and arm circumference (r = ?0.26, p = 0.037 and r = ?0.25, p = 0.047, respectively).ConclusionThe results indicate that S100A1 and ZAG are likely to contribute to the pathogenesis of HF disease and weight loss, as well as the strong association between S100A1 and ZAG possibly indicating a similar mechanism of action for these two proteins.     

Carotid intimal medial thickness in rotating night shift is related to IL1β/IL6 axis

Background and aimsSleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors.Methods and resultsWe measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y).R–NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1β levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489–4.776, p = 0.016).ConclusionsOur result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1β/IL6 citokine axis connected to sleep disturbances.     

Collagen triple helix repeat containing 1 (CTHRC1) protein: A promising biomarker for evaluation of rheumatoid arthritis patients

Aim of the workTo assess serum collagen triple helix repeat containing 1 (CTHRC1) protein level in rheumatoid arthritis (RA) patients and compare it with healthy controls. In addition, to evaluate the relation of its level with RA activity and severityPatients and methodsThe study included 60 adult RA patients and 60 matched controls. Disease activity score (DAS28), modified health assessment questionnaire (MHAQ) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. Serum CTHRC1 levels were measured in patients and controls by enzyme linked immunosorbent assay (ELISA)ResultsThey were 49 females and 11 males patients with a mean age of 43.6 ± 10.8 years and disease duration of 8.8 ± 0.9 years. The mean of DAS28 was 4.9 ± 2 (1.95–8.6). Serum CTHRC1 levels were significantly higher in patients than controls (1009.5 ± 79.4 vs. 470.7 ± 8.2 ng/ml, p < 0.001).The optimum cut-off value of CTHRC1 to discriminate patients from control was > 583.5 ng/ml with sensitivity of 98.3% and specificity of 100%. CTHRC1 significantly correlated with DAS28 (r = 0.81, p < 0.001), MHAQ (r = 0.14, p = 0.002), RARBIS (r = 0.41, p = 0.006), erythrocyte sedimentation rate (ESR) (r = 0.57, p < 0.001), C-reactive protein (CRP) (r = 0.41, p = 0.002), rheumatoid factor (RF) (r = 0.31, p = 0.037) and anti-cyclic citrullinated peptide (anti-CCP) (r = 0.27, p = 0.036). The significant predictors of increase CTHRC1 among patients were elevation in DAS28 (ß=287.6; p = 0.007, CI = 83.4–491.9) and MHAQ (ß=369.7; p = 0.042, CI = 14.5–724.9)ConclusionSerum CTHRC1 is a promising biomarker for evaluation of RA patients. It can be used as a marker for RA diagnosis and in monitoring the disease activity and severity.