Lupus

The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking.

To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE.

Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (¹⁴C-Phospolipid, ³H-Cholesteryl ester, ³H-Triglyceride, and ¹⁴C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants.

Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0 mg/dL; p < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99 mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18 mg/dL; p < .05, 75.05 ± 22.52 vs 96.05 ± 25.63 mg/dL; p < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70 mg/dL; p < .05, 75.05 ± 22.52 vs 88.53 ± 20.24 mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p = .066) were similar among groups.

The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.

Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of belimumab for SLE patients are not clear. Therefore, this meta-analysis is integrating the efficacy and safety of belimumab for patients with SLE.

PubMed, EMBASE, and Cochrane Library were searched for randomized clinical trials (RCTs) that studied the efficacy and safety of belimumab plus standard therapy before November 1, 2021. Data were pooled using the random-effects model and are expressed as risk ratios (RRs) or mean difference (MD) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I².

Seven RCTs with 3,009 participants were included in this meta-analysis. Belimumab showed significantly decreased at least a 4-point improvement in Safety of Estrogen in Lupus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score than placebo (RR, 1.32; 95% CI, 1.21–1.44; p < 0.001). However, belimumab significantly reduced the prednisone dose by 50% or more than placebo (RR, 1.59; 95% CI, 1.17–2.15; p = 0.003) and belimumab significantly increased the 36 Physical Component Summary (PCS) score (MD, 1.60; 95% CI, 0.30–2.90; p = 0.02). Regarding adverse events, there was no significant difference between the belimumab group and the control group.

The results suggest that belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients.

The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity.

The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger’s regression analysis were used to assess publication bias. Q statistics and I² test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model.

Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE.

IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.

We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity.

Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0–3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification.

The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group.

Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.

Although the significance of inflammatory cytokines and chemokines in the pathogenesis of SLE is well established, the findings showed diversity and implied that combining different biomarkers could be useful in monitoring disease activity or organ involvement. Despite the potentially high prevalence of lung involvement in SLE, only a few studies have investigated for lung biomarkers.

The aim of this study was to assess the value of Chemokine Ligand 21 (CCL 21) and Interferon gamma–induced protein 10 (IP10) as serum biomarkers for pulmonary involvement in SLE and their correlation with disease activity, organ involvement, pulmonary function tests (PFTs), and chest CT findings.

Sixty SLE patients and 30 age- and sex-matched controls were enrolled into this study. All patients underwent serological tests, PFTs, and chest CT examination. The serum levels of CCL21 and IP10 were analyzed, and their correlations with PFTs and CT were explored.

SLE patients with pulmonary involvement had higher serum CCL21 and IP10 levels compared to those without pulmonary involvement which in turn had higher levels than the controls. There were strong negative correlations between CCL21 and IP10 and FEV1, FVC, and DLCO. There were also strong correlations between both biomarkers and HRCT and pulmonary damage, but no correlation with other disease manifestations. Serum level of 2095 pg/mL for CCL21 and 7185 pg/mL for IP10 could detect pulmonary involvement in SLE with a sensitivity of 83.7% and a specificity of 94.1%. Both biomarkers performed equally well in detecting SLE pulmonary involvement with a strong agreement between them (κ = 0.86, p < .001), but CCL21 was better correlated with PFT abnormalities.

Both CCL21 and IP10 are serum biomarkers to detect pulmonary involvement in SLE with high sensitivity and specificity. CCL21 correlates better with PFT abnormalities.

To examine the long-term renal outcomes of systemic lupus erythematosus (SLE) patients with transient proteinuria.

The medical records of SLE patients who showed improvement in proteinuria (urine protein/creatinine ratio < 500 mg/g) after receiving corticosteroid therapy without immunosuppressants were reviewed.

A total of 38 patients (mean creatinine: 0.74 ± 0.33 mg/dl) showed an improvement of proteinuria (1361 ± 1053 mg/g to 289 ± 125 mg/g) after receiving corticosteroid therapy alone for a median of 25 days (IQR, 10–55). After follow-up (median, 23 months [IQR, 15–121]), 25 (65%) patients maintained the resolution of proteinuria without renal dysfunction. The remaining 13 (34%) patients experienced a relapse of proteinuria during a median follow-up of 13.9 months from baseline (IQR, 1.6–25). There was no significant difference in the baseline laboratory data according to the occurrence of proteinuria relapse, but longer SLE disease duration at baseline was associated with the risk of proteinuria relapse (HR, 1.007; p = 0.033). Of the patients who underwent renal biopsy with proteinuria relapse, class II (53%) lupus nephritis was the most common pathology. None progressed to end-stage renal disease during an additional long-term further follow-up of median 33 months (IQR, 22–49) after proteinuria relapse.

Two-thirds of SLE patients who showed improvement in proteinuria after corticosteroid alone maintained the non-proteinuric state without renal dysfunction. Thus, performing a kidney biopsy at the first onset of proteinuria could be delayed in patients who show an improvement in proteinuria after treatment with corticosteroids.

Although liver dysfunction is not considered the main organ involvement in Systemic Lupus Erythematosus (SLE), the frequency of liver dysfunction or abnormal liver enzyme values may be observed in 50–60% of patients. The aim of this study was to assess fatty liver and liver fibrosis in SLE patients using Fibroscan as well as determine associated factors such as immunosuppressive medications.

Sixty SLE patients and 30 healthy controls were included. Patients with HBV, HCV or cirrhosis, malignancy, cardiac disease, or patients on dialysis were excluded. All participants underwent Fibroscan measurements.

The prevalence of fatty liver disease was similar between SLE patients and healthy controls (21.7 vs 26.7%, p = .597). Liver fibrosis was also similar between the two groups (26.7 vs 10.0%, p = .069). Since the majority of SLE patients were female, we performed a subgroup analysis in female patients (n = 51) and controls (n = 25). Fatty liver disease was similar between female SLE patients and controls (23.5 vs 24.0%, p = .964). However, liver fibrosis in female patients with SLE was increased compared to female controls (29.4 vs 4.0%, p = .011) and was associated with age (Exp (B) 95% CI: 1.083 (1.006–1.166), p = .034) and low-dose cumulative glucocorticoid use (Exp (B) 95% CI: 14.116 (1.213–164.210), p = .034).

The prevalence of fatty liver was similar between SLE patients and controls, while liver fibrosis was increased in the female patient group as compared to controls. Furthermore, liver fibrosis was associated with age and low dose cumulative glucocorticoid use. Interestingly, fatty liver did not precede liver fibrosis in the majority of cases, contrary to what is observed in the general population. Larger studies are needed to confirm our findings and determine whether immunosuppressive use has any impact on the development of liver fibrosis in SLE patients.

Anemia is common in patients with juvenile systemic lupus erythematosus (jSLE). While autoimmune hemolytic anemia (AIHA) is the only etiology included in the classification criteria, the etiology of anemia in jSLE may be diverse. We aimed to investigate the etiology of anemia in jSLE and the relationship between anemia and disease characteristics at onset and during the follow-up period.

Patients diagnosed with jSLE who met the Systemic Lupus Erythematosus International Collaborating Clinics classification criteria between January 2012 and December 2020 were retrospectively analyzed.

Hematologic involvement was observed in 70% of the patients. Anemia was the most common cytopenia among patients (60%). Anemia of chronic disease (ACD) and AIHA were the most common etiological factors, both observed in 23% of patients. Patients with anemia had a significantly higher rate of positive ds-DNA antibody and higher erythrocyte sedimentation rate (ESH) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. ESH, serum ferritin, and SLEDAI scores negatively correlated with hemoglobin levels in patients with anemia. Iron deficiency was the sole etiology of new-onset anemia. Patients with new-onset anemia during the follow-up period had significantly lower hemoglobin values at onset and a higher rate of renal involvement.

Anemia in jSLE is mostly AIHA and ACD, but iron deficiency is not rare. The severity of inflammation is associated with the severity of anemia. During the follow-up period, iron deficiency was the predominant cause of anemia, especially in patients with lower hemoglobin concentrations at onset and renal involvement.

The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to differ from that of adult-onset SLE.

We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset SLE in a cohort of Indonesian patients at tertiary care centers.

This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017. The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old) (Group 1) and adult-onset SLE (≥18 years old) (Group 2).

Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20% (174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients: hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001) were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in childhood-onset group (11.5% vs 7.0%, p = 0.208).

Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the need for more aggressive management approach to childhood-onset patients with SLE.