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.     

Renal arterial resistive index as a noninvasive biomarker of disease activity in lupus nephritis patients

Aim of the workTo evaluate the renal resistive index (RI) in lupus nephritis (LN) patients and to study its association with clinical features, laboratory investigations and LN pathological classes in systemic lupus erythematosus (SLE) patients.Patients and methodsThe study included 45 SLE patients and 25 matched controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into LN (renal SLEDAI ≥ 4) and no-renal activity (NRA) (renal SLEDAI = 0). Ultrasound Doppler renal examination was done to measure RI. Renal biopsies were performed in 30 LN patients.ResultsThe mean age of patients was 29.8 ± 10.1 years and disease duration 4.3 ± 3.9 years. They were 40 females and 5 males (F:M 8:1). Their SLEDAI was 10.9 ± 8.2 and renal SLEDAI was 5.2 ± 5.1. They were 30 with LN and 15 NRA SLE patients. Renal RI was significantly higher in LN patients compared to NRA SLE patients and controls (0.61 ± 0.04 vs. 0.55 ± 0.01 vs. 0.55 ± 0.02; p < 0.0001). RI significantly correlated with anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity (r = 0.33, p = 0.03), 24-hour proteins in urine (r = 0.38, p = 0.01) and negatively with creatinine clearance (r = -0.33, p = 0.03). Renal RI significantly correlated with pathological classes of renal biopsy (r = 0.65, p < 0.0001). At renal RI cut-off value 0.57 renal RI can detect renal activity with sensitivity of 83.3%, specificity of 82.5%, p < 0.0001. Renal RI ≥ 0.57 had higher activity index score compared to those with normal RI (5.7 ± 0.6 vs. 9 ± 3.3, p = 0.04). Conclusion: Renal RI was significantly increased in LN compared to NRA patients and was associated with laboratory parameters and pathological classes.     

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.     

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.     

Impact of psycho-educational therapy on disease activity,quality of life,psychological status,treatment satisfaction and adherence in systemic lupus erythematosus patients

Aim of the workTo evaluate the impact of group psychotherapy and patient education on disease activity, quality of life, psychological symptoms, perceived stress, satisfaction to treatment, and medication adherence in systemic lupus erythematosus (SLE) patients.Patients and methodsThis study recruited 80 SLE patients divided equally into intervention and control groups, the intervention group received 12 sessions of group psychotherapy and patient education. SLE disease activity index (SLEDAI) was assessed. The following questionnaires were conducted: Symptom Checklist-90-Revised (SCL-90-R), perceived stress scale (PSS), Short Form 36 (SF36), Treatment Satisfaction Questionnaire for Medications (TSQM), and Medication Adherence Rating Scale-5 (MARS-5).ResultsThe mean age of the patients was 32.3 ± 7.4 years and disease duration 7.5 ± 5.7 years. They were 77 females and 3 males. At baseline, the SLEDAI, global severity index of SCL-90-R, PSS, SF36, TSQM and MARS-5 were comparable between both groups. After 3 months of the psycho-educational program, the intervention group exhibited significant improvement of SCL-90-R: anxiety (p = 0.052), depression (p = 0.002), global severity index (p = 0.001), PSS (p < 0.001), SF36 [limitations due to emotional problem (p < 0.001), emotional well-being (p < 0.001), MCS (p = 0.029), PCS (p = 0.001)], TSQM [effectiveness (p < 0.001), convenience (p = 0.026), side effects (p = 0.001), global satisfaction (p = 0.005) scores] and MARS-5 (p < 0.001) with no significant difference in SLEDAI (p = 0.802).ConclusionIntegration of a psycho-educational program in the management of SLE patients was associated with improvement of depression, anxiety, perceived stress, quality of life, satisfaction with treatment, and medication adherence, with no impact on disease activity.     

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.     

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.     

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.     

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.     

Utero-placental and cerebrovascular indices in pregnant women with systemic lupus erythematosus: Relation to disease activity and pregnancy outcome

Aim of the workTo assess maternal and fetal vascular indices in SLE patients during pregnancy, and the impact of disease activity on these vascular indices.Patients and methods30 pregnant SLE patients and 30 age -matched healthy females with uncomplicated pregnancies were assessed during the third trimester using ultrasonography (US) and Doppler study to detect fetal biometry, the uterine, umbilical (UA) and fetal middle cerebral (MCA) arterial resistance (RI) and pulsatility (PI) indices, as well as cerebro-placental ratio (CPR). Disease activity was determined using the SLE Disease Activity Index (SLEDAI).ResultsThe mean uterine artery PI, RI and the UA-PI in SLE group were significantly higher than controls (p value < 0.001), but no significant difference as regards UA-RI (p = 0.68) between both groups. There was unilateral uterine artery notch in 20% and bilateral in 6.7% while it was absent in 73.3%. The MCA-PI was significantly lower in SLE group (p = 0.003), Where the MCA-RI showed higher values than control (p < 0.001). The CPR showed a lower significant values for SLE group compared to controls (p < 0.001), while the PR interval was significantly higher in SLE group (p = 0.006). Fetal biometry showed no significant difference between two groups apart from higher abdominal circumference (AC) values in controls (p = 0.01). There was no significant correlation between abnormal vascular indices or biometric parameters and SLEDAI score (p > 0.05).ConclusionPregnancies in SLE are associated with abnormal maternal and fetal vascular indices. Doppler US can identify at-risk pregnancies and optimize the time of delivery; confirming a good pregnancy outcome.     

Effect of body weight on pain,sleep quality,and depression in patients with primary fibromyalgia syndrome

Aim of the workObesity and fibromyalgia syndrome (FMS) are two diseases, which are becoming more common and have an impact on social life. This study aimed to evaluate the effect of body weight on pain, sleep quality, and depression in patients with primary FMS and to assess its impact on the functional status.Patients and methodsThe study included 234 patients with primary FMS. The body mass index (BMI) was determined. The visual analog scale (VAS), Beck depression inventory (BDI), and the Pittsburgh sleep quality index (PSQI) were used for evaluating the patients. The Fibromyalgia impact questionnaire (FIQ) was assessed. The patients were divided into 3 groups: normal weight, overweight and obese.ResultsThe mean age of the patients was 40.3 ± 11.01 years (19–65 years); 206 (88%) were female, and 28 (22%) were males. The mean BMI was 28.8 ± 7.1 (17.7–49.1): 80 (34.2%) had a normal weight (24.4 ± 1.8), 76 (32.5%) were overweight (26.4 ± 1.6), and 78 (33.3%) were obese (37.9 ± 5.9) (p < 0.001). The FIQ, BDI, and PSQI were significantly higher in the obese patients compared to the normal and overweight (p < 0.001). The BMI, VAS, BDI, and FIQ were comparable between females and males while only the PSQI was significantly reduced in males (p = 0.004). A significant correlation was found between BMI with the PSQI, BDI, and FIQ (r = 0.11, p = 0.009; r = 0.41, p < 0.001 and r = 0.35p < 0.001 respectively).ConclusionObesity in primary FMS patients was significantly related to pain, sleep disorders, and depression. The importance of movement and weight control in FMS is emphasized.     

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.     

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.     

Coronary Vessel Wall Contrast Enhancement Imaging as a Potential Direct Marker of Coronary Involvement: Integration of Findings From CAD and SLE Patients

ObjectivesThis study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk.BackgroundCoronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall.MethodsA total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area.ResultsCoronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05).ConclusionsWe demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk.     

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.     

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.     

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.     

The association between adipokines and stigmata of atherosclerosis in patients with systemic lupus erythematosus

Aim of the workEarly cardiovascular disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The study was designed to assess the relationship between the serum levels of adipokines and atherosclerotic risk factors in SLE patients.Patients and methods56 patients and 31 control were included. Serum levels of leptin, adiponectin, traditional and new risk factors for atherosclerosis including plasma glucose levels, lipid profile, high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) and homocysteine were measured. The intima-media thickness (IMT) of the carotid was measured by ultrasonography. The SLE disease activity index (SLEDAI-2k) was assessed.ResultsThe patients mean age was 30.8 ± 9.9 years, disease duration was 55.7 ± 59.3 months and were 54 (91.5%) females and 5 (8.5%) males. Serum adiponectin levels were significantly lower in patients (3.58 ± 0.4 ng/ml) compared to control (3.9 ± 0.26 ng/ml) (p < 0.001) while leptin levels were comparable. Serum adiponectin levels correlated with triglyceride (r = 0.3, p = 0.003) and high-density lipoprotein (HDL) (r = 0.2, p = 0.04). Serum leptin significantly correlated with the BMI and total cholesterol (r = 0.43, p = 0.002 and r = 0.3, p = 0.04 respectively) as well as with the anti-double stranded deoxyribonucleic acid (anti-dsDNA) (r = 0.28, p = 0.04). There was lack of a meaningful relationship between serum adiponectin and leptin levels and disease duration or risk factors such as hsCRP, VCAM, homocysteine and IMT as well as with the SLEDAI-2k or complement.ConclusionsSerum adiponectin levels inversely correlate with HDL. A significant correlation of leptin with BMI and total cholesterol was found in SLE. None of the two adipokines were associated with atherosclerosis as assessed with the carotid IMT or with the disease activity.     

Quality of sleep in rheumatoid arthritis patients: Relationship with disease activity,depression and functional status

Aim of the workTo assess sleep quality in Egyptian patients with rheumatoid arthritis (RA) and its relationship with disease activity, depression and functional status.Patients and methodsThis cross-sectional study included 133 RA patients and 76 age and sex matched controls. Sleep using the Pittsburg Sleep Quality Index (PSQI), Beck depression inventory (BDI), functional status using health assessment questionnaire (HAQ), visual analogue scale-pain (VAS), and disease activity score (DAS28) were assessed.ResultsPatients were 125 females and 8 males with a mean age of 42.5 ± 9.5 years and disease duration of 3.9 ± 1.3 years. 76 age and sex matched control were also included. Poor sleep quality was detected in 54.1% of patients. Patients had significantly higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, day-time dysfunction domains and in terms of the total PSQI score compared to the control (p < 0.05). A significant difference was found between RA patients with poor sleep quality and those with good sleep quality as regards marital status, HAQ, erythrocyte sedimentation rate (ESR), VAS, DAS28, morning stiffness duration, anti-cyclic citrullinated peptide (anti-CCP) (p < 0.05), and the BDI (p < 0.001). The multivariate regression analysis found that disease activity, functional disability and depression were predictors for poor sleep quality (p = 0.04, p = 0.01 and p < 0.001; respectively).ConclusionThe sleep quality is impaired in RA patients. The poor sleep quality is associated with disease activity, depression and functional disability. Systemic psychiatric screening, holistic assessment and targeted interventions are required to improve sleep quality and quality of life.     

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.