Serum cystatin C and ßeta-2 microglobulin as potential biomarkers in children with lupus nephritis.

Objectives: In this study, we aimed to assess serum levels of Cystatin C (Cys C) and beta-2 microglobulin (ß2M) in juvenile systemic lupus erythematosus (JSLE) patients and to investigate their role as potential biomarkers of lupus nephritis (LN) and overall disease activity. Patients and methods: Between December 2018 and November 2019, a total of 40 patients with JSLE (11 males, 29 females; mean age: 12.6±2.5 years; range, 7.5 to 16 years) and 40 age- and sex-matched controls (10 males, 30 females; mean age: 12.3±2.4 years; range, 7 to 16 years) were included in this study. Serum (s) Cys C and ß2M levels were compared between the groups. The SLE Disease Activity Index (SLEDAI-2K), the renal SLEDAI (rSLEDAI), and the Renal Damage Index were used. Results: JSLE patients had significantly elevated mean sCyc C and sß2M levels (1.4±0.8 mg/mL and 2.8±0.9 mg/mL, respectively) compared to the controls (0.6±0.1 mg/mL and 2.0±0.2 mg/mL, respectively; p<0.00). The mean sCys C and sß2M levels were significantly higher in the LN group, compared to non-LN patients (1.8±0.7 mg/mL and 3.1±1.0 mg/mL, respectively vs. 0.8±0.3 mg/mL and 2.4±0.6 mg/mL, respectively; p=0.002 and p=0.02, respectively). The sCys C levels had significant positive correlations with erythrocyte sedimentation rate (r=0.3, p=0.05), serum creatinine (r=0.41, p= 0.007), 24-h urinary protein (r=0.58, p<0.001), anti-double stranded deoxyribonucleic acid antibodies titers (r=0.55, p=0.002), extra-renal SLEDAI scores (r=0.36, p=0.04), rSLEDAI (r=0.46, p=0.002), and renal class (r=0.7, p=0.0001). Serum ß2M levels were significantly negatively correlated with complement 4 levels (r=-0.31, p=0.04) and significantly positively correlated with extra-renal SLEDAI scores (r=0.3, p=0.05). Conclusion: These findings confirm that sCys C and sß2M levels are increased in JSLE patients in association with the overall active disease. However, sCys C level may act as a promising non-invasive biomarker for predicting kidney disease activity and biopsy classes in children with JSLE.

Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences.

OBJECTIVES: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). METHODS: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. RESULTS: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), and mSASSS (p=0.003). ASDAS - CRP was the only significant predictor of hypovitaminosis D in AS patients. CONCLUSION: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.

Concomitant Diagnosis of Fibromyalgia and Ankylosing Spondylitis: Relation to Clinical Features and Plasma Pentraxin -3 Level.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disease that specifically affects the spine and sacroiliac joint. AS diagnosis is often delayed in the clinical practice and this delay may cause the patients to miss the chance of early treatment. Fibromyalgia (FM) is a frequently encountered clinical syndrome, fibromyalgianess is a term used when patients who are diagnosed with inflammatory arthropathies meet the criteria for FM syndrome as shown in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, and AS. OBJECTIVES: We aimed primarily to assess the frequency of concomitant diagnosis of FM syndrome in AS patients and study its impact on clinical disease aspects. Secondary, our aim extended as a preliminary pilot study to assess the Plasma Pentraxin-3(PTX-3) as a potential marker for the diagnosis of FM syndrome in AS patients. METHODS: Plasma PTX-3 in 61 AS patients was compared to 60 matched controls. FM was diagnosed by FM Rapid Screening Tool. Bath AS disease activity index (BASDAI) and AS disease assessment score using C- reactive protein (ASDAS-CRP), Bath AS functional impairment index (BASFI), Bath AS metrology index (BASMI), AS quality of life (ASQoL) scale, Beck Depression Inventory, and Bath AS Radiology Index (BASRI) were assessed. RESULTS: The patients were categorized into two groups according to the concomitant diagnosis of FM syndrome. Group I included 14 (22.9%) AS patients who fulfilled the clinical diagnosis of FM syndrome. Group II included 47 (77.1%) AS patients without FM syndrome. AS patients with FM (Group I) had significantly(p<0.001) increased an average of ages, disease duration, diagnostic delay of AS, switching of bDMARDs, morning stiffness duration, ASDAS-CRP, BASFI, ASQoL score, BASDAI (p=0.008), and BDI score (p=0.005) compared to AS patients without FM (Group II). PTX-3 levels were significantly (p<0.001) higher in Group I (p<0.001) (median, 0.23; IQR, 0.15-0.41 ng/ml) than Group II (median, 0.13; IQR, 0.035-0.21ng/ml) which showed no significant differences (p>0.05) compared to the controls. PTX-3 levels had significant positive correlations (p<0.05) with disease duration, BASFI, and ASQOl. Age, female sex, switch of biologic, ASDAS - CRP, and PTX-3 were significant predictors of FM in AS patients. CONCLUSION: These results indicate that concomitant FM is a significant problem in patients with AS and its presence is associated with higher disease activity, impaired function as well as an overall negative impact on QoL. Easy scanning of suspicious cases of FM with FiRST questionnaire can be done in daily practice. PTX-3 is more or less accurate as the clinical features to improve the diagnostic certainty of FM in the presence of AS with a proven sensitivity of 62.3%, a specificity of 90%, a positive predictive value of 82.75%, and a negative predictive value of 73.9%.

Assessment of Endocan Serum Level in Patients with Behçet Disease: Relation to Disease Activity and Carotid Intima Media Thickness.

Behçet disease (BD) is a form of vasculopathy that can influence blood vessels of variable diameters. Endocan is a biomarker of endothelial activation and it is secreted from endothelial cells as a soluble proteoglycan. The aim of the work was to assess endocan serum level in patients with BD and to examine its relationship with disease activity parameters and carotid intima media thickness (IMT). The study encompassed 42 patients with BD (25 males and 17 females) diagnosed according to the International Study Group Criteria of BD and 42 age and sex matched apparently healthy volunteers as controls. Human Endothelial cell-specific Molecule-1 (Endocan) was assessed using ELISA. Carotid mean IMT was calculated by Color Doppler ultrasonography. Thickness measurement more than 1 mm was considered abnormal:BD patients had significantly increased endocan serum levels (median, 249.5; IQR, 174 - 445 ng/l) compared to healthy controls (median, 190.5; IQR, 128 - 235 ng/l, P=0.002), endocan serum level was increased in BD patients with active disease (median, 434; IQR, 246 - 617.5 ng/l) compared to those with inactive disease (median, 195.5; IQR, 145 - 235 ng/l, P < 0.001) and healthy controls (P < 0.001). Endocan serum levels showed significant positive correlations with erythrocyte sedimentation rate (P=0.04), C-reactive protein (P < 0.001), BD Current Activity form (P < 0.001) and carotid IMT (P=0.008). In conclusion, Endocan can be used to monitor disease activity and endothelial dysfunction in BD.

Serum Soluble CD163 and its association with various disease parameters in patients with systemic sclerosis.

OBJECTIVE: Cluster of differentiation 163 (CD163) is a receptor that binds haptoglobin-hemoglobin complexes and is mainly expressed on macrophages and monocytes. As a result of shedding, the extracellular portion of CD163 circulates in the blood as a soluble CD163 (sCD163). This study aimed to measure serum sCD163 levels in patients with systemic sclerosis (SSc) and to assess its association with the clinical, laboratory, and radiological features of the disease. MATERIAL AND METHODS: We measured serum sCD163 levels in 24 patients with SSc and in 30 healthy controls. Complete history of the patients was recorded and thorough clinical, rheumatological, and dermatological examinations were performed. For SSc, the skin thickness score was scored according to the modified Rodnan skin score method and pulmonary involvement was assessed in all patients using high-resolution computed tomography and by performing pulmonary function tests. RESULTS: The mean serum sCD163 levels in patients with diffuse and limited SSc (61.64±19.57 and 60.8±21.43 ng/mL, respectively) demonstrated a highly statistically significant increase compared with the mean serum levels in healthy controls (36.97±16.37 ng/mL) (p<0.001). Patients with SSc having elevated serum sCD163 levels had significantly higher pulmonary artery systolic pressure (PASP) than those with normal serum sCD163 levels (p<0.05). Furthermore, the serum sCD163 levels were significantly correlated with PASP (r=0.53, p<0.05) in patients with SSc. The mean serum sCD163 level in patients with SSc having digital ulceration (DU) (70.82±18.3 ng/mL) demonstrated a statistically significant increase (p<0.05) compared with that in SSC patients without DU (53.23±18.09 ng/mL). CONCLUSION: The elevated serum sCD163 levels in patients with SSc and its association with pulmonary hypertension suggest a possible role of macrophages in the pathogenesis and vascular involvement of SSc.

Interleukin-18 gene polymorphisms in systemic lupus erythematosus: relation to disease status.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by loss of self-tolerance causing immune-mediated tissue destruction and various clinical presentations Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. This study investigates polymorphisms of the IL-18 gene in SLE patients at positions -607 and -137 of the promoter to elucidate their possible roles in the activity and severity of this disease. Fifty SLE patients and fifty unrelated healthy control group were included. AII SLE patients underwent thorough clinical examination and SLE disease activity assessment using SLEDAI. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR analysis were used to genotype the DNA samples for SNP-607and SNP-137, while plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay. The frequency of SNP-607/CC genotype showed significant increase (P < 0.05), while genotype SNP-607/CA showed significant decrease (P < 0.05) in SLE patients as compared to the control group. Significantly elevated levels of plasma IL-18 were found in patients compared to controls (P < 0.001) and those with genotype CC at -607 demonstrated the highest IL-18 level (331.74 +/- 36.48 pg/mL). Serum IL-18 levels showed significant positive correlations with the ESR 1st hr. (r = 0.89), protein/creatinine ratios (r = 0.88), anti-dsDNA titers (r = 0.44) and SLEDAI scores (r = 0.91). In contrast, significant negative correlations were found with HB% r = -0.68, creatinine clearance (r = -0.87) and C3 (r = -0.81). In addition, a statistically significant association was found between IL-18 of CC -607 genotype and lupus nephritis, arthritis and immunological disorders. In conclusion, IL-18 promoter gene polymorphisms at position -607 may contribute to SLE activity and accelerate SLE development by enhancing production of IL-18 protein in SLE patients.