Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity.Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients.ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038).ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.     

Implications of blood indices in systemic lupus erythematosus patients: Two feasible determinants of disease activity and lupus nephritis

Aim of the workTo investigate whether or not neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may by indicators of disease activity in systemic lupus erythematosus (SLE) with and without lupus nephritis (LN).Patients and methodsThis research was carried out on 40 adult SLE patients (20 with LN and 20 without) and 20 controls. The NLR and PLR were calculated. The SLE disease activity index (SLEDAI) was assessed.ResultsThe mean age of the patients was 36.2 ± 7.6 years, 38 females and 2 males (F:M 19:1), with a disease duration of4.3 ± 1.2 years. The mean SLEDAI was 15.1 ± 4.7 being significantly higher in those with LN (17.5 ± 3.5) compared to those without (12.6 ± 4.6) (p = 0.001). The mean NLR (6.1 ± 2.1) and PLR (236.6 ± 86.9) were significantly increased in patients compared to the control (2.7 ± 1.2 and 125.2 ± 38.8 respectively) (p < 0.001). The NLR and PLR were both significantly related to the serum creatinine (r = 0.35, p = 0.03 and r = 0.5, p = 0.001) and SLEDAI (r = 0.36, p = 0.03 and r = 0.34, p = 0.03 respectively). NLR can significantly predict activity of SLE at cut off 5.6 with a sensitivity 80%, specificity 65% (p = 0.007) and PLR at cut off 217 with sensitivity 75%, specificity 65% (p = 0.035). The NLR can significantly predict LN at cut off 3.6 (sensitivity 80%, specificity 40%; p = 0.007) and PLR at cut off 186 (sensitivity 70%, specificity 60%; p = 0.035).ConclusionThere is a remarkable link between PLR and NLR with SLEDAI. Thus, both may serve as promising affordable indicators of inflammation in SLE. The notable relation to LN may signal renal involvement in patients with SLE.     

Serum level of CXCL 12 in patients with systemic lupus erythematosus: Is it worthy for predilection of lupus nephritis?

Aim of the workTo assess serum level of CXCL12 in systemic lupus erythematosus (SLE) patients and to study its relation to clinical features, disease activity and damage.Patients and methodsForty SLE patients and 40 controls were included. SLE disease activity index (SLEDAI) and the damage index were assessed. Serum CXCL12 level was measured using ELISA and renal biopsy done.ResultsThe mean age of the patients was 34.5 ± 10.4 years, disease duration 5 ± 5.2 years and were 38 females and 2 males (F:M 19:1). Renal biopsy was performed in 16 patients; 6 had inactive and10 active lupus nephritis (LN); 24 without signs suggestive of LN. Serum level of CXCL12 was significantly higher in patients (30.8 ± 16.9 ng/ml) than controls (20.2 ± 15.3 ng/ml) (p = 0.004). CXCL12 in patients with active LN (53.2 ± 25.3 ng/ml) was significantly elevated than those without LN (27 ± 12.5 ng/ml)(p < 0.001); and tended to be higher than those with inactive LN (34.2 ± 8.3 ng/ml)(p = 0.31). Levels were comparable between those with inactive LN and those without LN (p = 0.34). A significant correlation was found between serum CXCL12 and each of platelet count (p = 0.02), ANA titer (p = 0.007) and serum creatinine (p = 0.014). No significant correlations was found between CXCL12 and either SLEDAI (p = 0.59) or the damage index (p = 0.48). Alopecia was inversely associated with CXCL12 (p = 0.02).ConclusionCXCL12 is a potential key-player for SLE development. Adding this test to ANA, serum creatinine, platelet count and renal biopsy findings may enhance their diagnostic capacity for lupus nephritis and can help in early management and prediction of its prognosis.     

Tumor necrosis factor-α, its related immunoregulatory long non-coding RNA (THRIL) and micro-RNA 145 as potential biomarkers in lupus nephritis patients

Aim of the workTo explore the differential expression of tumor necrosis factor-α (TNF-α), its related immunoregulatory long non-coding RNA (THRIL), and microRNA145 (MIR145) in systemic lupus erythematosus (SLE) patients and their diagnostic utility in lupus nephritis (LN).Patients and methodsThe study included 60 SLE patients; 30 with LN, 30 without LN (NN), and 30 matched controls. SLE disease activity index was assessed. Serum TNF-α level was determined by enzyme linked immunosorbent assay. Serum fold change (FC) in expression of THRIL and MIR145 were assayed by real time polymerase chain reaction.ResultsThe patients mean age was 32.6 ± 6.8 years and were 52 females and 8 males (F:M 6.5:1). Serum TNF-α level was significantly higher in SLE patients (108.6 ± 47.8 pg/ml) compared to control (39.6 ± 3.7 pg/ml) (p < 0.001). THRIL expression was upregulated (8.3 ± 6.9 vs. 1.02 ± 0.06 FC, p < 0.001) and MIR145 downregulated (0.39 ± 0.36 vs. 0.92 ± 0.94 FC, p < 0.001) in SLE patients versus controls. THRIL correlated with disease activity (r = 0.27, p = 0.035) and MIR145 with C3 (r = −0.32, p = 0.04) and C4 (r = −0.36, p = 0.016) levels in SLE patients. In LN patients, TNF-α and THRIL were increased while MIR145 downregulated (p < 0.001 each) and proteinuria significantly correlated with TNF-α (r = −0.4,p = 0.028), THRIL (r = 0.48, p = 0.007) and MIR145 (-0.42, p = 0.02). In NN patients, TNF-α and THRIL (p < 0.001 both) were increased while MIR145 downregulated (p = 0.023). TNF-α (cutoff ≥ 122.5 pg/ml, AUC 0.67, p = 0.003), and MIR145 (cutoff ≤ 0.22 FC, AUC 0.71, p = 0.026) discriminated LN from NN. The combination of TNF-α and MIR145 discriminated better than either alone (AUC 0.75, p = 0.002).ConclusionTNF-α and MIR145 are potential biomarkers of LN 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.     

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p < 0.001). There were significant correlations between IL-18 and SLEDAI (p = 0.002), proteinuria (p = 0.027), renal activity score (p = 0.003) and activity index (p = 0.039) in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN.ConclusionIL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE.     

Clinical significance of interferon lambda-3 (IFNλ3)/interleukin 28B (IL28B) in systemic lupus erythematosus patients

BackgroundInappropriate and excessive activation of type I interferon (IFN) system is a key feature of systemic lupus erythematosus (SLE), and its targeting has led to important achievements in the development of novel drugs for SLE.Aim of the workTo evaluate the serum levels of interferon lambda IFNλ3 (IL28B) in Egyptian patients with SLE and investigate its potential relation with different clinical and laboratory parameters.Patients and methodsThe study included 40 SLE patients and 40 controls. The SLE disease activity index (SLEDAI) was assessed. The measurement of serum levels of IFNλ3 was performed in all participants using enzyme linked immunosorbent assay (ELISA).ResultsThe mean age of the patients was 26.8 ± 7.8 years with disease duration 5.1 ± 4.5 years and they were 35 females and 5 males. The serum levels of IFNλ3 were significantly higher in SLE patients (9.7 ± 12.47 pg/mL) compared to the control (5.13 ± 1.63 pg/mL)(p = 0.02). Significant correlations were observed between serum IFNλ3 and serositis (r = 0.35,p = 0.03), C3 consumption (r ?0.33, p = 0.04) and SLEDAI (r 0.34, p = 0.03). On multivariate regression analysis, serositis and SLEDAI (but not C3) were significant independent predictors of IFNλ3 levels (β = 0.08, p = 0.037 and β = 0.06, p = 0.014 respectively).ConclusionThe results support a possible role of IFNλ3/IL28B in the immunopathogenesis of SLE. The significant association of serum IFNλ3 with disease activity highlights the utility of IFNλ3 as a novel biomarker for monitoring disease activity and predicting severity in SLE. Further studies on IFNλ3 in SLE could be promising in the development of personalized therapy for lupus patients.     

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.     

Sexual dysfunction and physical performance in female systemic lupus erythematosus patients

Aim of the workTo investigate the sexual dysfunction in systemic lupus erythematosus (SLE) patients and its relation to physical fitness and other disease parameters.Patients and methodsThe study included 47 SLE females and 47 matched healthy controls. SLE disease activity index (SLEDAI) and systemic lupus international collaborative clinics damage index (SLICC DI) were assessed. Physical performance of the patients was assessed by the grip ability test (GAT), gait velocity test, Jebsen hand function test, fatigue severity scale (FSS) and the modified health assessment questionnaire (mHAQ). Sexual dysfunction of the patients was assessed by the sexual function index (FSFI). Depressive disorders of the patients were assessed by Beck depression inventory.ResultsThe mean age of the patients was 28.7 ± 7.2 years and disease duration 4.4 ± 2.9 years. GAT was significantly lower (43.65 vs 70.00; p = 0.001), and FSS higher (6.5 vs 1; p = 0.001) in patients compared to control. The total FSFI was significantly lower (23.41 vs 29.60; p = 0.001) and all domains scores were significantly lower except the pain domain (p = 0.001). Beck depression inventory score was higher in patients (13.29 vs 12.74; p = 0.365). SLE females with prescribed corticosteroids and azathioprine had significantly lower FSFI as compared to those without while FSFI score was higher in those receiving hydroxychloroquine. The FSFI significantly correlated with C4 level (r = 0.328, p = 0.024 and inversely with, SLEDAI (r = ?0.07, p = 0.001), FSS (r = ?0.54, p = 0.001), mHAQ (?0.37, p = 0.01) and with Beck depression inventory (r = ?0.57, p = 0.001).ConclusionMarried female patients with SLE revealed a higher degree of sexual dysfunction of all domains except pain.     

Potential role of high sensitivity cardiac troponin T in subclinical coronary atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo determine the role of high sensitivity cardiac troponin T (HS cTnT) in subclinical coronary atherosclerosis in SLE patients at an apparent low risk for CVD according to traditional risk factors.Patients and methodsThe presence of subclinical coronary atherosclerosis was assessed by non-contract coronary computerized tomography and calcium score was measured using Agatston score in 30 SLE patients asymptomatic for CVD and 30 age and sex matched apparently healthy controls. SLE disease activity index (SLEDAI) was assessed. Serum HScTnT concentration was measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean age of the patients was 33 ± 5.7 years, disease duration of 33.7 ± 22 months and mean SLEDAI 8.1 ± 5.02. The mean HS cTnT level was 12.8 ± 11.3 ng/L (1–36 ng/L). Their Framingham score was 4.8 ± 3.1 (1–12). Framingham score was low in both SLE patients (range 1–12%) and controls (1–9%) (p = 0.12). 11 (36.7%) patients, but none of the controls, had coronary artery calcification (CAC). Serum HScTnT concentration was detectable (>3 ng/L) in 16 (53.3%) patients and 2 (6.7%) control (p < 0.001). Interestingly, it was detectable in all patients with CAC, but in only 26.3% of patients without (p < 0.001). HScTnT significantly correlated with Agatston (r = 0.63, p = 0.04), with erythrocyte sedimentation rate (r = ?0.65, p = 0.03), and with C-reactive protein (r = 0.76, p = 0.03) in SLE patients with CAC.ConclusionSerum HScTnT level is high and associated with CAC in SLE patients who are at an apparently low risk for CVD according to the Framingham risk score. HS cTnT may be a useful biomarker for SLE-associated subclinical atherosclerosis.     

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.     

Clinical significance of platelet-lymphocyte ratio in systemic lupus erythematosus patients: Relation to disease activity and damage

Aim of the workTo assess platelet–lymphocyte ratio (PLR) in systemic lupus erythematosus (SLE) patients and study its clinical significance, its relation to disease activity and damage.Patients and methodsThis study included 52 adult SLE patients and 50 matched control. All patients were subjected to full clinical examination, disease activity was measured by SLE disease activity index (SLEDAI), and damage was assessed by using Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). Laboratory and immunology profiles included the complete blood count (CBC) with differential white blood cell (WBC) counts and estimation of PLR, erythrocyte sedimentation rate (ESR), liver and kidney function, alkaline phosphatase (ALP), serum calcium (Ca) and phosphorous (P), lipid profile, 24hr urinary protein, renal biopsy, anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), serum complements (C3,C4).ResultsThe mean age of SLE patients was 33.1 ± 9.2 years (20–58 years), with mean disease duration of 5.4 ± 5.02 years (0.25–20 years). The PLR was significantly higher in patients (189.9 ± 136.4; 23.9–782.9) than control (95 ± 29.9; p < 0.0001). The WBC and platelets count was comparable between patients and control (7.1 ± 1.7 x10³/mm³ and 243.4 ± 51.3 x10³/mm³; p = 0.3 and p = 0.51 respectively). The lymphocytic count was significantly lower in patient compared to control (1.9 ± 1.1 x10³/mm³ vs 2.7 ± 0.8 x10³/mm³)(p < 0.0001). PLR would significantly predict activity (p = 0.02) with a sensitivity of 94.3% and specificity of 100% at a cut-off value of 33.6. There was no association of PLR with the damage index.ConclusionPLR might be considered a valuable and un-expensive tool in assessment and prediction of SLE disease activity.     

Relation of some clinical composite indices of disease activity in rheumatoid arthritis to a simplified 12 joint power Doppler ultrasound activity index

Aim of the workTo assess the association of some clinical composite disease activity indices with a simplified 12 joint power Doppler ultrasound (PDUS) activity index in rheumatoid arthritis (RA).Patients and methodsOne hundred RA patients who fulfilled the 2010 European league against rheumatism/American college of Rheumatology (EULAR/ACR) classification criteria for RA were recruited from the Rheumatology outpatient clinic, Cairo University Hospitals. Disease activity score (DAS28), the simplified disease activity index (SDAI), clinical disease activity index (CDAI) as well as mean overall index for RA (MOI-RA) were assessed. Grey Scale Ultrasonography (GSUS) and PDUS activity assessment was performed using a simplified 12-joint score.ResultsThe 100 patients were 80 females and 20 males (F:M 4:1). Their mean age was 44.4 ± 10.8 years with disease duration of 6.3 ± 4.7 years. Rheumatoid factor was positive in 77 %. DAS28 was 4.5 ± 1.3, SDAI 27.7 ± 22.7, CDAI 17.5 ± 13.2 and MOI-RA 86.8 ± 25.1. On US, tenosynovitis was present in 10 %, irregularity in 23 % and erosion in 62 %. The mean 12-point PDUS was 3.53 ± 4.16 and the overall US score 10.34 ± 9.3. A significant correlation was found between the US findings of overall synovitis, degree of PD and US score with DAS28 (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.3, p < 0.0001) with SDAI (r = 0.3, p < 0.0001; r = 0.4,p < 0.0001; r = 0.4, p < 0.0001) and with MOI-RA score (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.4, p < 0.0001 respectively) but the highest correlations was with CDAI (r = 0.4, p < 0.0001; r = 0.5, p < 0.0001 and r = 0.4, p < 0.0001 respectively).ConclusionSimplified 12 -joint PDUS score is well correlated with activity indices in RA patients.     

Clinical significance of interleukin-36 alpha and gamma in systemic lupus erythematosus patients: Potential relation to disease activity and subclinical arthritis

Aim of the workTo assess serum of interleukin-36 alpha (IL-36α) and interleukin-36 gamma (IL-36γ) levels in systemic lupus erythematosus (SLE) patients and to explore their association with clinical and laboratory features of SLE and with ultrasound evidence of subclinical hand arthritis.Patients and methodsThe study included 84 SLE patients without overt arthritis and 84 matched controls. The serum levels of IL-36α and IL-36γ were measured and compared between patients and controls. The hands and wrists of all patients underwent musculoskeletal ultrasound evaluation for evidence of subclinical arthritis and tenosynovitis. The SLE disease activity score was assessed for all patients.ResultsThe mean of serum IL-36α (65.5 ± 38.9 pg/ml) and IL-36γ (468.9 ± 315.9 pg/ml) were significantly higher in SLE patients compared to controls (37.9 ± 17.2 pg/ml and 151.1 ± 73.4 pg/ml; p < 0.001 each). IL-36α and IL-36γ had the ability to discriminate between SLE patients and controls with an AUC of 0.69 and 0.83 respectively. Serum IL-36α was significantly correlated with SLEDAI score (p = 0.04), synovitis (p < 0.001),Us erosion score (p = 0.01) and PD signals score (p = 0.002). Serum IL-36γ was significantly correlated with serum creatinine level (p = 0.04). SLE patients with arthralgia had significantly higher IL-36α serum level than patients without (p = 0.04). SLE patients with proteinuria had significantly higher IL-36γ than those without (p = 0.04). The linear regression analysis model revealed that the US evidence of synovitis was the strongest factor associated with the serum level of IL-36α meanwhile proteinuria was the strongest factor associated with the serum level of IL-36γ.ConclusionIL-36αserum level was significantly associated with SLEDAI score, arthralgia and US evidence of subclinical arthritis. IL-36γ serum level was significantly associated with proteinuria.     

Evaluation of visfatin in patients with systemic lupus erythematosus: Correlation with disease activity and lupus nephritis

IntroductionRenal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients. The adipokine “visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease.Aim of the workTo assess serum visfatin level in SLE patients and its correlation to disease activity and lupus nephritis (LN) in these patients.Patients and methodsSerum level of visfatin using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of SLE and LN were measured in 40 SLE patients and 40 age and sex matched healthy controls. Disease activity and renal involvement were assessed using SLE Disease Activity Index (SLEDAI) and Renal SLEDAI respectively further dividing patients into active versus inactive and LN versus non-LN respectively. Renal biopsies were taken from LN subgroup and were classified according to the modified WHO classification.ResultsA significantly higher serum visfatin level was found on comparing SLE patients (mean 109 ± 180 ng/ml, median18) with controls (mean 9.4 ± 11 ng/ml, median2.5) with statistically highly significant difference (z = 5.2, P < 0.001). Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173 ± 111 ng/ml, median 14) and inactive patients (mean 139 ± 88 ng/ml, median 5) (z = 2.1, P < 0.05) as well as between patients with LN (mean 226 ± 180 ng/ml, median18) and patients with no LN (mean 101 ± 140 ng/ml, median 8(2-229)) (z = 2.1, P < 0.05). Visfatin had a highly significant positive correlation with disease duration (r = 0.48, P < 0.001), SLEDAI (r = 0.62, P < 0.001) as well as ESR, CRP and, renal score (r = 0.45, 0.35, and 0.65, respectively) while inverse correlation with estimated GFR (r = ?0.614) and C3 and C4 titre (r = ?0.26, r = ?0.35, respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE and LN 83% and 85%, respectively.ConclusionSerum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score and GFR decline. Further prospective studies are required to confirm visfatin as a destructive mediator of predictive and prognostic value in active lupus nephritis.     

Programmed death 1 (PD-1) serum level and gene expression in recent onset systemic lupus erythematosus patients

Aim of the workTo investigate the potential association of protein programmed death 1 (PD-1) serum level and its gene expression inrecent onset systemic lupus erythematosus (SLE) patients and study its association with the disease activity.Patients and methodsThe study included 80 recently diagnosed SLE patients and 80 healthy controls. SLE disease activity index (SLEDAI) was assessed. The serum level of soluble (sPD-1) was assessed by enzyme linked immunosorbent assay (ELISA) and its gene expression level was evaluated by real time-polymerase chain reaction (RT-PCR).ResultsThey were 68 females and 12 males (F: M 5.7:1) with age 30.8 ± 8.7 years and disease duration of 3.2 ± 1.7 months. The sPD-1 and PD-1 gene expression level (folds) were significantly elevated in patients (1280.6 ± 1448.1 pg/ml and 0.3 ± 0.06 folds) than controls (109.1 ± 11.9 pg/ml and 0.03 ± 0.008 folds) (p < 0.001). A significant correlation was found between sPD-1 and hematuria, pyuria, fever and C3 level (p = 0.01, p = 0.001, p = 0.02, and p = 0.03 respectively), and between PD-1gene expression and psychosis and fever (p = 0.03, p = 0.014). No significant correlation was found between SLEDAI and PD-1 gene expression or sPD-1 level (p = 0.1, p = 0.23 respectively). No significant correlation was found between sPD-1 and PD-1 gene expression levels and the autoantibodies.ConclusionPD-1 gene expression as well as the serum level of sPD-1 are elevated significantly in recent onset SLE patients denoting that they may have a role in the pathogenesis of the disease while there was no relation to the disease activity. This biomarker may be potentially promising for the development of a novel lupus immunotherapy by targeting the PD-1 pathway.     

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.     

Patterns of microRNAs 142-3p, 106a, 17 and 20a expression in patients with systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) is a connective tissue disorder which involves immune system dysregulation. Micro-ribonucleic acids (MiRNAs) up and down regulation are implicated in its development.Aim of the workTo examine the expression levels of certain miRNAs (miR-17, miR-20a, miR-106a, and miR-142-3p) in SLE patients and to investigate which miRNAs are involved in the pathogenesis of SLE, in order to be used as diagnostic or prognostic biomarkers.Patients and methods60 patients and 60 matched control were included. SLE disease activity index 2000 (SLEDAI-2 K) was assessed. Assessment of serum miRNAs was done using real-time quantitative polymerized chain reaction.ResultsThe median age of patients was 29.5 years (24–32) and they were 59 females and 1 male with a median disease duration of 24 (20–48) months and SLEDAI of 5.5 (2.3–9). miR-17a, miR-142, miR-20a and miR-106a were significantly lower in patients (22.5 ± 2.2; 22.8 ± 2.2; 23.4 ± 2.4 and 22.6 ± 2.2) compared with control (23.8 ± 2.1; 24.7 ± 2.2; 25.1 ± 2.4 and 24.4 ± 2.3) (p = 0.002, p < 0.001, p < 0.001 and p < 0.001 respectively). The 4 markers significantly correlated with the SLEDAI (p = 0.002; p = 0.002; p = 0.004 and p = 0.001 respectively). The diagnostic capability of miR-142, miR-20a and miR-106a in predicting SLE showed a specificity of 95%, 98% and 90% at cut-off values of >22.6, >22.1 and >22.8 respectively; area under the curve was 67, 72, 70 and 76% at p-values p = 0.19, p < 0.001, p < 0.001, p < 0.001 respectively.ConclusionMiR-17, miR-142-3p, miR-20a, and miR-106a have a diagnostic value in SLE and may serve as a therapeutic target for treatment. The studied markers were also related to the disease activity.