Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN. AIM OF WORK: Investigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology. PATIENTS AND METHODS: A case-control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated. RESULTS: Urinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005). CONCLUSION: Urinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4. Key Points • Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients. • It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN. • A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN. • Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.

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.

Anti-vinculin antibodies as a novel biomarker in Egyptian patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder that causes vasculopathy and scarring, most commonly in the lungs and skin, but it can also affect other organs. Endothelial vinculin plays a critical role in angiogenesis regulation. Therefore, vinculin overexpression in SSc may give rise to anti-vinculin antibodies, which may contribute to the development of SSc vasculopathy. The current research aims to (1) determine whether anti-vinculin autoantibodies play a significant role in the diagnosis of SSc and (2) compare anti-vinculin serum levels between two scleroderma patient populations, namely, pulmonary artery hypertension (PAH)-predominant and interstitial pulmonary fibrosis (IPF)-predominant groups. METHODS: This research included 140 participants categorized into three groups: group I-patients with PAH-predominant; group II-patients with ILD-predominant; group III-the control group. Anti-vinculin antibodies were detected in serum samples collected from all participants using ELISA. All subjects underwent high-resolution computed tomography (CT), diffusing capacity for carbon monoxide, and pulmonary function tests. RESULTS: Patients in group I (PAH-predominant group, N = 35) were 41.3 [± 11.4] years old, with 80% being women. Patients in group II (ILD-predominant group, N = 35) were 41.0 [± 11.5] years old. The SSc group showed significantly higher anti-vinculin antibody levels than the control group (P < 0.001). The PAH-predominant group demonstrated significantly higher anti-vinculin antibody levels and anti-vinculin positivity than the ILD-predominant group. CONCLUSION: Anti-vinculin antibodies in the blood appear to be diagnostic biomarkers for scleroderma. Furthermore, they shed light on some novel perspectives on the pathophysiology of specific lung fibrotic changes. Key Points • This study included two groups of systemic sclerosis patients (PAH-predominant group, ILD-predominant group) as well as a control group to investigate the significance of anti-vinculin antibodies in such cases. • Our results have demonstrated that anti-vinculin antibodies can play a significant role in diagnosing and monitoring systemic sclerosis disease.

Role of PTPN22 1858 C/T Polymorphisms in Juvenile Idiopathic Arthritis in Egyptian Patients.

Juvenile idiopathic arthritis (JIA) the most common chronic arthropathy of childhood is a diverse group of chronic arthritis diseases. The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T and B cells. This study aimed to study PTPN gene polymorphism in JIA. The study included 60 children with JIA and 40 age and sex matched healthy children as controls. Patients and control groups were subjected to PTPN gene polymorphism analysis. Our findings indicated a significant difference in PTPN22 polymorphism between JIA patients and the control group (P = 0.021). Different PTPN genotypes were studied in relation to patient's age, sex and relevant laboratory data. It was concluded that PTPN22 polymorphism is different in JIA patients than healthy controls. T allele is associated only in cases with JIA and it may be considered as risk allele for certain JIA subtypes.

Correlations between ultrasonographic findings, clinical scores, and depression in patients with knee osteoarthritis.

OBJECTIVE: This study aimed to explore correlations between the presence of depression, clinical scores, and ultrasonographic (US) grading in osteoarthritis (OA) patients and to clarify if depressive symptoms might cause a discrepancy between US findings and clinical scores. MATERIAL AND METHODS: Two hundred patients with primary knee OA and 100 healthy hospital volunteers of the same age and sex not complaining of knee troubles participated in this study. We evaluated depressive symptoms in all participants using the Beck Depression Inventory (BDI) scale. Thorough clinical examination was performed, including assessment using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) for disability. All patients underwent US examination of their affected knees. RESULTS: Depression was detected in 60 patients with knee OA (30%) and in 5 controls (5%). The mean of BDI score was 12.8±12.2 in OA patients and 5.8±3.2 in controls, and this difference was statistically significant (p=0.03). Correlations of BDI with both body mass index (BMI) (p=0.04) and Numerical Rating Scale of Pain (NRSP) score (p=0.006) were significant, while correlations of BDI with both the ages of our patients (p=0.74) and their disease duration (p=0.88) were insignificant. There were statistically significant correlations between patients' disease duration and US measurements regarding osteophyte length, lateral femoral cartilage thickness, medial femoral cartilage thickness, and thickness of the quadriceps tendon despite of the presence of insignificant correlations between disease duration and both the effusion volume and volume of Baker's cysts. There were statistically significant correlations between patients' disease duration and US measurements except for effusion volume and volume of Baker's cysts. There were statistically significant correlations between the NRSP score in OA patients and BDI (p=0.006) and all US measurements apart from lateral femoral cartilage thickness, medial femoral cartilage thickness, and thickness of quadriceps tendon. There were statistically significant correlations between BDI in OA patients and the WOMAC (p=0.005), Kellgren-Lawrence (KL) grading (p=0.034), and US grading (p=0.041). CONCLUSION: The presence of knee effusion, Baker's cysts, osteophytes, and high BMI have a great impact on the pain and disability associated with OA. Higher clinical scores, radiographic scores, and US scores correlate with the emergence of depression in OA patients.

Decrease of serum biomarker of type II Collagen degradation (Coll2-1) by intra-articular injection of an autologous plasma-rich-platelet in patients with unilateral primary knee osteoarthritis.

OBJECTIVE: This study aimed to evaluate the effect of one dose of intra-articular injection of (PRP) in the knee joint on a specific osteoarthritis (OA) serum biomarker of cartilage degeneration, Collagen 2-1 (Coll2-1), over a short period of 3 months. The aim extended to clarify the effect of PRP on the functional status of the osteoarthritic knee joint. MATERIAL AND METHODS: Sixty patients with primary unilateral knee OA were enrolled in this study. They were subdivided according to Kellgren-Lawrence grading scale (KL) into (Group I): including patients with KL grade < 3 and (Group II): including patients with KL grade ≥3. Patients were asked to complete the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score. PRP was prepared and injected immediately into the affected knee. Serum Coll2-1 (S.Coll2-1) concentration was measured by enzyme-linked immunosorbent assay (ELISA) kit pre and 3 months after PRP injection. RESULTS: Significant reduction in S.Coll2-1 concentration in primary knee OA patients; (p<0.001) and (p<0.05) in group I and group II respectively as well as significant improvements in WOMAC total and WOMAC sub-scores values were noted after single intra-articular PRP injection with maximal functional improvements were achieved after 3 months (p<0.001). Mild cases experienced favorable results with no remarkable adverse reactions were observed. CONCLUSION: Reduction in specific OA biomarker S.Coll2-1 following intra-articular PRP injection emphasize that PRP could be a promising safe and tolerable effective therapeutic option which improves function from basal states in primary knee OA patients.

Serum calreticulin as a novel biomarker of juvenile idiopathic arthritis disease activity.

OBJECTIVE: This study aimed to investigate the relations between calreticulin (CRT) serum level and both disease activity and severity parameters in juvenile idiopathic arthritis (JIA). MATERIAL AND METHODS: In this study, 60 children with JIA and 50 age-and-sex-matched healthy subjects were enrolled. The assessment of the disease activity was done using juvenile arthritis disease activity score 27 (JADAS-27). The assessment of disease severity was done via gray-scale ultrasonography (US) and power Doppler US (PDUS). Enzyme-linked immunosorbent assay (ELISA) was used to assay the serum level of human CRT. RESULTS: The mean serum CRT levels in JIA patients was 8.6±1.2 ng/mL and showed a highly significant increase (p=0.001) as compared to the mean serum levels in the controls (5.02±0.77 ng/mL). There were statistically significant positive correlations between the serum CRT levels and disease duration, tender joint count, swollen joint count, visual analog scale, erythrocyte sedimentation rate, JADAS-27, C-reactive protein, rheumatoid factor titer, and ultrasonographic grading for synovitis and neovascularization. CONCLUSION: Elevated serum CRT levels in JIA patients and its correlations with JIA disease activity and severity parameters signified that CRT might be used as a novel biomarker for disease activity and severity in JIA.

Expression of IL-23 mRNA in Systemic Lupus Erythramtosus Patients: Relation with Disease Activity.

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. Cytokine-mediated immunity involved in the pathogenesis of SLE. Recently, IL-23 was proposed to play a crucial role in mediating tissue inflammation and autoimmunity. The present work was aimed to investigate the relation between levels of IL-23 mRNA and disease activity in patients with SLE and in those with renal involvement. In this work, blood samples from 45 adult patients with SLE and 20 healthy controls were collected. Patients were divided into 3 groups. Group I consisted of 16 patients with active SLE with nephritis. Group II consisted of 13 patients with active SLE without nephritis. Group III consisted of 16 patients with inactive SLE based on the SLE disease activity index (SLEDAI). The IL-23 mRNA relative concentration was detected by Quantitative Reverse transcriptase- polymerase Chain Reaction (RT-PCR). IL-23 mRNA expression level in blood was eleven times higher in SLE patients without activity while in active SLE patients with and without nephritis showed 34 fold and 17 fold higher IL-23 mRNA expression respectively compared to healthy control. IL-23 mRNAs levels were significantly higher in patients with SLE compared with healthy controls (P < 0.001). Patients with active disease showed higher IL-23 mRNAs compared with those with inactive disease as well as healthy controls (P < 0.001). IL-23 levels were significantly higher in SLE patients with renal involvement compared with those without renal disease (P < 0.001). It is concluded that IL-23 has a role in the development and pathogenesis of SLE & lupus nephritis.

Interleukin-18 promoter polymorphisms in Egyptian patients with rheumatoid arthritis.

The aim of this study was to investigate the association of interleukin-18 (IL-18) promoter single nucleotide polymorphisms (SNPs) at - 607 and - 137 regions with risk for rheumatoid arthritis (RA) and their association with activity and severity of the disease. The study included 80 RA patients and 80 age and sex matched healthy subjects. Forty RA patients and 40 control subjects were randomly chosen to measure their serum IL-18 levels. IL-18 SNPs at - 607 and - 137 regions were analyzed using polymerase chain reaction-sequence specific polymorphism (PCR-SSP) analysis. The frequency of -137CC genotype was significantly lower in RA patients than controls (OR = 0.23, 95% CI 0.07-0.72, p = 0.012), while the -607C/A genotypes (CC, CA, AA) showed insignificant differences between patients and controls. No association was found between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (HB), DAS 28 and X ray grades and -607C/A and - 137G/C genotypes. Serums levels of IL-18 were not significantly different among individuals with different IL-18 -607 and -137 genotypes. It is concluded that RA is negatively associated with IL-18 -137CC SNP, and that IL-18 607-SNPs may not be a risk factors for RA in Egyptian patients with no specific genotype association with disease activity or severity. No specific genotype was associated with higher IL-18 serum levels.