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.     

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.     

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.     

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.     

Disease damage in systemic lupus erythematosus patients: Disease activity,male gender and hypertension as potential predictors

Aim of the work: To identify factors associated with damage in systemic lupus erythematosus (SLE) patients. Patients and methods: Based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI) patients were divided into 2 groups; patients with damage (SDI ≥ 1) and without (SDI = 0). Groups were compared regarding demographic features, co-morbidities, cumulative clinical features, treatment and assessment of the modified SLE disease activity index (M?SLEDAI) at baseline and every 6 months till the end of follow up.Results: The study included172 patients; 152 (88.4%) females and 20 (11.6%) males with a mean age of 35.5 ± 8.6 years and disease duration of9.8 ± 1.2 years.Eighty-five (49.4%) patients had damage with a mean SDI of 1.04 ± 1.36. The musculoskeletal, renal and neuropsychiatric systems were damaged in 17.4%, 12.8% and 10.4% of patients, respectively. A comparison between patients with and without damage identified male gender (p = 0.001); older age (p = 0.002), age at onset (p < 0.001); hypertension (p = 0.001); renal (p = 0.007) and neuropsychiatric involvement (p = 0.019); vasculitis (p = 0.044); M?SLEDAI last-visit (p = 0.004), average M?SLEDAI (p = 0.007), number and frequency of visits with active disease (p < 0.001 for both); number of flares (p = 0.001); use and cumulative dose of pulse steroids (p < 0.001 and p = 0.042, respectively), overall cumulative steroid dose (p = 0.007), cyclophosphamide use (p < 0.001), hydroxychloroquine dose (p = 0.029) and less use of leflunomide(p = 0.01) as factors associated with damage. On multivariate regression, the association between damage and male gender (p = 0.02), hypertension (p = 0.016) and number of visits with active disease (p = 0.002) was retained. Conclusion: Male gender, hypertension and prolonged disease activity in SLE contribute to damage occurrence.     

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.     

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.     

Impact of antiphospholipid syndrome on disease characteristics and outcome in patients with systemic lupus erythematosus

Aim of the workTo assess the impact of antiphospholipid syndrome (APS) on systemic lupus erythematosus (SLE) clinical characteristics and disease outcome.Patients and methods216 SLE patients were classified according to the presence of APS into: SLE group (n = 109) and SLE-APS (n = 107). Evaluation of clinical, laboratory tests, immunological tests, SLE disease activity index 2000 (SLEDAI-2 K) and SLE damage index (SDI) were done.ResultsThe 216 patients mean age was 32.1 ± 8.4 years and the F:M was 8.4:1. There was a significantly higher frequency of abortion, neurological and cardiac manifestations (p < 0.001, p = 0.008, p = 0.016 respectively) in SLE-APS group. The SDI was significantly higher in SLE-APS patients (p < 0.001) with special attention to the presence of cerebrovascular accident (CVA) (p = 0.01), pulmonary hypertension (p = 0.04), cardiomyopathy (p = 0.034) and venous thrombosis (p < 0.0001). The frequency of thrombosis and active SLEDAI-2 K visits were significantly related to higher damage in SLE-APS (p < 0.001 and p < 0.001 respectively). Damage in SLE group was associated with hypocomplementemia (p = 0.015) and thrombosis (p = 0.049). Factors associated with damage in all SLE patients were male gender (p = 0.024), serositis (p = 0.02), neurological involvement (p < 0.001), thrombotic events (p < 0.001), cumulative doses of oral (p = 0.02) and pulse (p = 0.004) steroids and frequency of cyclophosphamide (CYC) use (p = 0.003). Predictors of damage included male gender, APS, neurological manifestations, use of steroids and CYC (p = 0.045, OR = 8.5; p < 0.0001, OR = 4.3; p = 0.001, OR = 6.3; p = 0.047, OR = 1.03; p = 0.005, OR = 2.96, respectively).ConclusionAPS adversely affect SLE disease course with prominent impact on end organ damage especially cerebral, cardiopulmonary and vascular events denoting the need for strict control of disease activity and early diagnosis.     

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.     

Audiologic evaluation in systemic lupus erythematosus patients and impact of hydroxychloroquine therapy

Aim of the work: To evaluate the hearing function in systemic lupus erythematosus (SLE) patients and assess the impact of chronic use of hydroxychloroquine (HCQ). Patients and methods: This study was conducted on 48 SLE patients and 12 matched controls. The SLE disease activity index (SLEDAI) was assessed. Otological manifestations and extended high frequency audiometry were assessed. SLE patients were divided into those receiving HCQ (n = 36) and those not (n = 12). Results: The mean age of the patients was 39.5 ± 9.7 years, 40 females and 8 males, median disease duration was 7 (1.5–20) years. The median (interquartile range) SLEDAI was 4 (2.75). The median daily dose of those receiving HCQ was 400 mg. There was a significant difference regarding patients reported otological manifestations such as tinnitus (p = 0.02), vertigo (p = 0.002) and hearing impairment (p = 0.04) compared to controls but not for deafness or ear buzzing in one or both ears. There was a significant decrease in the hearing threshold frequencies between patients and controls (p < 0.001). Those receiving HCQ showed more hearing impairment at frequency 9000 and 20,000 Hz than those not (p = 0.004, p < 0.001 respectively). The otological manifestations were comparable between those receiving HCQ and those not. There was no difference between those receiving 400 mg/day (n = 31) HCQ and those receiving 200 mg/day (n = 5) Conclusion: Otological symptoms and sensorineural hearing loss are frequent among SLE patients. Chronic administration of HCQ may have an ototoxic effect.     

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.     

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

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

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.     

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.     

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.     

Hospitalization and outcome of systemic lupus erythematosus patients admitted to the Rheumatology ward of Kasr Al-Ainy University Hospital

Aim of the workTo determine the frequency, causes and disease features affecting outcome of hospitalized systemic lupus erythematosus (SLE) patients, length of hospital stay and the risk factors.Patients and methods132 SLE patients accounting for 167 hospitalizations were recruited from the Rheumatology outpatient clinic, Faculty of Medicine, Cairo University Hospitals during 2019. SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC-DI) were assessed. Data concerning admission was recorded.ResultsThe mean age of the patients was 31.4 ± 10.7 years and disease duration of 91.5 ± 84.3 months. Their mean SLEDAI was 8.7 ± 7.2 and SLICC-DI was 0.87 ± 1.2. The frequency of hospitalization was 167/1456 follow up visits (11.5%): 127 single admissions and 40 recurrent admissions. 137 hospital admissions were females and 30 males (F:M 4.6:1).The most common causes of hospitalization were disease activity in 115/167 hospital admissions (68.9%), infection in 39/167 (23.4%), comorbidities in 33/167 (19.8%). Outcome of hospitalization was improvement in 154/167 (92.2%), morbidity in 7/167 (4.2%), and mortality in 5/167 (3%). Readmission occurred in 40/167 (24%). Higher SLEDAI and gastrointestinal involvement were risk factors for longer hospital stay (p = 0.001 and p = 0.003 respectively). Morbidity was related to higher SLEDAI and SLICC-DI while mortality was related to prolonged azathioprine intake and cardiovascular involvement.ConclusionDisease flare and infection were the most common causes of hospitalization among SLE patients. Higher disease activity and damage as well as cardiovascular involvement were the factors associated with worse outcome. Higher SLEDAI and gastrointestinal involvement were risk factors for longer hospital stay.     

Impact and associations of lymphopenia in a cohort of Egyptian systemic lupus erythematosus patients: Potential link to complement (C3) and corticosteroids

Aim of the workTo investigate the relation between lymphopenia and clinical disease activity, disease associated end organ damage, laboratory markers and medications received in systemic lupus erythematosus (SLE) patients. Another objective was to investigate the prognostic value of lymphopenia.Patients and methodsThe medical records of 698 SLE patients under follow-up at the Rheumatology clinics of Cairo and KafrElsheikh University hospitals were revised. Demograghic and laboratory data, SLE disease activity index (SLEDAI), damage index and drug history were assessed.ResultsMean age of 28.4 ± 8.8 years (12–60 years), they were 640 females and 58 males (F:M 11:1) and a disease duration of 6.2 ± 4.7 (0.1–31 years). The study included 674 adults and 24 juvenile cases. 280 (40%) had lymphopenia. Patients with lymphopenia had significantly consumed complement 3 (C3) (p < 0.001), C4 (p = 0.002) and anticardiolipin IgG (p = 0.05). Patients with lymphopenia had a significantly higher incidence of infections (p < 0.001), antiphospholipid antibodies (p = 0.014), frequent intake of cyclophosphamide (p = 0.001), pulse steroid therapy (p < 0.001) and other drugs (p = 0.009) including IVIG and plasmapheresis. Univariate regression model revealed the predictive potential of consumed C3, anticardiolipin IgG, cyclophosphamide, pulse steroid therapy, steroids > 40 mg/day, infections, antiphospholipids for associated lymphopenia. On multivariate analysis only consumed C3 (p = 0.008) and pulse steroid therapy (p = 0.036) remained as independent risk factors for lymphopenia.ConclusionLymphopenia may be more than a hematological finding in SLE patients that was found to be associated with complement consumption, high steroid doses and cyclophosphamide administration, infections and antiphospholipids. The key independent risk factors for lymphopenia are pulse steroid and C3.