Serum amyloid A-to-albumin ratio as a potential biomarker to predict the activity, severity, and poor prognosis of systemic lupus erythematosus.

OBJECTIVES: To evaluate the predictive value of serum amyloid A-to-albumin ratio (SAR) for active systemic lupus erythematosus (SLE), severe active SLE, and poor prognosis of SLE. METHODS: One hundred and eighty-six patients with SLE undergoing treatment in our hospital were selected. The demographic characteristics, clinical data, and disease prognosis of all patients were collected and analyzed. RESULTS: There were significant differences in SLEDAI, total glyceride (TG), serum amyloid A (SAA), SAR, urinary microalbumin-to-creatinine ratio (ACR), erythrocyte sedimentation rate (ESR), albumin (ALB), complement 3 (C3), anti-dsDNA, anti-Sm positive rate, and anti-dsDNA positive rate between active SLE and stable SLE patients. TG, SAR, C3, ACR, and positive anti-dsDNA were independent influencing factors of active SLE, and the odds ratio (OR) values were 2.342, 10.921, 0.832, 1.451, and 2.476, respectively. The area under curves (AUCs) of SAA, ALB, and SAR for predicting active SLE and severe active SLE were 0.743, 0.724, 0.787, 0.711, 0.686, and 0.733, respectively. The AUC of SAR for predicting the poor prognosis of active SLE was 0.719. High SAR, high ACR, low C3, and positive anti-dsDNA were high risk factors for poor prognosis. Kaplan-Meier (K-M) survival analysis showed that patients with high SAR, high ACR, low C3, and positive anti-dsDNA had shorter continuous remission time than that with low SAR, low ACR, high C3, and negative anti-dsDNA. CONCLUSION: SAR had high predictive value for active SLE, severe active SLE, and poor prognosis of SLE. High SAR may be a potential marker for predicting the activity and prognosis of Chinese patients with SLE.

PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus.

BACKGROUND: To assess the value of peptidoglycan recognition protein 2 (PGLYRP2) in assessing the disease activity and lipid metabolism in patients with systemic lupus erythematosus (SLE). METHODS: SLE patients with stable disease (n = 15), active lupus nephritis (LN) (n = 15) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (n = 15) admitted to Northern Jiangsu People's Hospital (Jiangsu, China) in 2019-2020 were recruited. In addition, volunteers with matched age and sex (n = 15) were enrolled as controls. The level of PGLYRP2 in the serum and its expression in peripheral blood mononuclear cells (PBMCs) were measured. The link between PGLYRP2 level and clinical parameters (including lipid profile) was described. RESULTS: Serum PGLYRP2 level in SLE cases exceeded that in healthy volunteers (3938.56 ± 576.07 pg/mL), and significantly higher in active LN (5152.93 ± 446.13 pg/mL) and NP-SLE patients (5141.52 ± 579.61 pg/mL). As shown by quantitative real-time PCR results, the expression of PGLYRP2 in PBMCs of SLE patients with active LN and NP-SLE surpassed that in healthy volunteers (P < 0.01). Receiver operating characteristic (ROC) curves demonstrated that PGLYRP2 was capable of distinguishing stable SLE from active LN (AUC = 0.841, 95%CI = 0.722-0.960, P = 0.000). PGLYRP2 level positively correlated with SLEDAI of SLE patients (r = 0.5783, P < 0.01). Moreover, its level varied with serological and renal function parameters (complement 3, complement 4, estimated glomerular filtration rate and 24-h urine protein) and immunoglobulin A (IgA) of SLE. A potential correlation between PGLYRP2 level and lipid profile (HLD-c, Apo-A1 and Apo B/A1) was determined in SLE patients. The linear regression analysis indicated SLEDAI as an independent factor of PGLYRP2 level, with a positive correlation in between (P < 0.05). CONCLUSIONS: Serum PGLYRP2 level significantly increases in SLE patients, and is positively correlated to SLEDAI. Moreover, serum PGLYRP2 level is correlated with renal damage parameters and the abnormal lipid profile of SLE. PGLYRP2 could be used to predict SLE activity, dyslipidemia and cardiovascular disease risks in SLE patients.

Dysregulated serum lipid profile and its correlation to disease activity in young female adults diagnosed with systemic lupus erythematosus: a cross-sectional study.

BACKGROUND: Recent studies showed that dyslipidemia could be a critical factor in the progression of cardiovascular disease in systemic lupus erythematosus (SLE). The aim of the present study was to describe the relationship between serum lipid profile and SLE disease activity in young female adults with SLE. METHODS: Seventy-one female subjects diagnosed with SLE aged 20~30 years were enrolled. Serum lipid profile including TC, TG, HDL-C, LDL-C, VLDL-C, Apo A, Apo B, and Apo E were evaluated between control and young female SLE patients. Univariate correlation analyses were performed to explore the correlation between serum lipid levels and SLE disease activity. RESULTS: Our results showed that TG and VLDL-C levels were significantly increased in young female SLE as compared to control, with TC, HDL-C, LDL-C, Apo A, and Apo B significantly reduced. Meanwhile, univariate correlation analyses showed negative correlations between SLE disease activity index and HDL-C, LDL-C, Apo A, and Apo B; with positive correlations between SLE disease activity index and TG and VLDL-C. CONCLUSION: Serum lipid profile was significantly dysregulated in young female SLE patients. Moreover, SLE disease activity was correlated to the serum lipid levels, supporting the notion that the young patients with SLE might also have a higher risk of cardiovascular disease.

Organ system improvements in Japanese patients with systemic lupus erythematosus treated with belimumab: A subgroup analysis from a phase 3 randomized placebo-controlled trial.

Objectives: To assess the effects of belimumab on disease activity across multiple organ domains in Japanese patients from the Phase 3 randomized, double-blind, North-East Asia study, BEL113750 (NCT01345253).Methods: Patients, aged ≥18 years, with American College of Rheumatology-defined systemic lupus erythematosus (SLE) and a Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥8 at screening, on stable SLE treatment, were randomized 2:1 to receive intravenous belimumab 10 mg/kg or placebo, plus standard of care, on Days 0, 14, and 28, then 4-weekly until Week 48. Patients were assessed for SELENA-SLEDAI and British Isles Lupus Assessment Group (BILAG) organ system improvement/worsening between baseline and Week 52.Results: Sixty patients (belimumab, n = 39; placebo, n = 21) were enrolled in Japan. Improvement was seen in a greater proportion of belimumab patients, compared with placebo, in most SELENA-SLEDAI and BILAG domains (significant for the mucocutaneous domain). Worsening occurred in SELENA-SLEDAI hematologic and renal systems (<7% both treatments) and in a number of BILAG systems: <11% (placebo) and <8% (belimumab), although the small sample size should be noted.Conclusion: Organ system improvements were seen in more Japanese belimumab-treated than placebo-treated patients, providing further evidence supporting belimumab use in Japanese patients with SLE.

High levels of circulating cell-free DNA are a biomarker of active SLE.

BACKGROUND: High levels of circulating cell-free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Comparative groups comprised 22 nonpregnant and 36 pregnant women with SLE (test groups) and 60 nonpregnant and 199 pregnant women with no history of SLE (control groups). The levels of cfDNA in plasma were quantitated by a fluorometric dsDNA assay. RESULTS: Compared to controls, the median levels of cfDNA were significantly higher in nonpregnant SLE patients (7.38 ng/mL vs 4.6 ng/mL, P = 0.033) and in pregnant SLE patients (7.65 ng/mL vs 5.25 ng/mL, P = 0.003). Based on SLE disease activity index (SLEDAI) scores, the median cfDNA levels were significantly higher in patients with active disease (4 < SLEDAI < 15) compared with patients with inactive disease (SLEDAI < 4) (13.58 ng/mL vs 6.72 ng/mL, P = 0.01). While there was a trend of increased cfDNA levels with higher SLEDAI scores (R2  = 0.3, P < 0.001), we found no association of increased cfDNA levels with nephritis, skin manifestations, multiorgan inflammations or with other inflammatory markers such as decreased C3 and C4 levels or increased anti-ds DNA antibodies. CONCLUSIONS: Our results suggest that in addition to classical SLE serological markers, measurement of circulating plasma cfDNA levels has potential as a useful biomarker for assessing SLE disease activity in patients and monitoring treatment.

Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex, incompletely understood, etiology. Several genetic and environmental factors are suspected to be involved in its aetiology. Oxidative stress may be implicated in the pathogenesis of SLE and may be affected by trace element status. Zinc (Zn), copper (Cu) and selenium (Se) are essential components of several anti-oxidative enzymes and are also involved in several immune functions. The current study aimed to assess the relationship between serum concentrations of these trace elements and the clinical disease activity of SLE assessed using the SLE disease activity index (SLEDAI). Serum concentrations of albumin (Alb) (p = 0.001), Se (p = 0.001), Zn (p = 0.001) and the Zn to Cu ratio (Zn/Cu R) (p = 0.001) were lower in patients with SLE than the age- and sex-matched healthy controls. However, only Alb (p = 0.001) and Cu (p = 0.03) were negatively correlated with disease activity, which was supported by regression analysis. In summary, lower serum values of Alb, Zn, Se and Zn/Cu R were found in SLE patients compared with healthy controls; however, in addition to serum Alb concentrations, serum Cu concentrations were also negatively correlated with lupus disease activity.

Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus.

BACKGROUND: The interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients. METHODS: We have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children's Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity. RESULTS: The TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE. CONCLUSION: The detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.

Significance of Interleukin 23 in Systemic Lupus Patients: Relation to Disease Activity and Damage Indices.

Background: Dysregulation of both cellular and humoral immune responses is central in systemic lupus erythematosus (SLE) pathogenetic mechanisms. Proinflammatory cytokines, such as interleukin 23 (IL23), and their roles in promoting such dysregulation have recently been highly considered. This research compared IL23 serum levels in 85 Egyptian SLE patients and 85 healthy controls. Then, IL23 level was correlated to various SLE disease parameters, disease activity, and damage indices. Results: IL23 serum levels were significantly elevated in SLE patients versus healthy individuals. Furthermore, IL23 levels were positively correlated with SLE disease activity index (SLEDAI) and were positively correlated with arthritis, seizures, consumption of complements (C3, C4), and with parameters of nephritis (hematuria, pyuria, casts, and proteinuria). A positive correlation was also found between IL23 levels and oral prednisolone dose. Conclusion: IL23 has higher levels in the serum of SLE patients, and is correlated to activity of the disease, especially lupus nephritis. Further researchis needed to explore its exact role in SLE pathogenesis and whether it can be considered a potential biomarker or therapeutic target in SLE.

Impact of anxiety and depression on disease activity and quality of life in patients with lupus nephritis.

Background of the Study: Lupus is an autoimmune disease that affects multiple body systems and requires long-term treatment. The multisystem effect of this disease and long treatment may cause anxiety and depression in patients with lupus nephritis (LN) and ultimately deteriorate their quality of life and also affects the activity of the disease. Aim of the Study: This study aims to assess anxiety, depression, and quality of life in patients with LN and their relationship with disease activity. Material and Methods: A descriptive cross-sectional study was conducted to assess anxiety, depression, and quality of life among patients with LN. A total enumerative technique was used for the recruitment of 100 patients and data collected using standardized tools were analyzed. Results: The results of the study showed that the majority of patients (60.0%) with LN had moderate anxiety and most of them (61.0%) had moderate depression that affected their quality of life and impacted the disease activity index in lupus. Conclusion: LN patients experience significant levels of anxiety and depression, which deteriorates their quality of life and negatively impacts disease activity. Active surveillance for these conditions and early diagnosis might help in the improvement of health-related outcomes in such patients.

Appraising SARS-CoV-2 infections after full mRNA COVID-19 vaccination in patients with systemic lupus erythematosus (SLE).

The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects - both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.

Impacts of FcγRIIB and FcγRIIIA gene polymorphisms on systemic lupus erythematous disease activity index.

OBJECTIVE: Systemic lupus erythematous (SLE) disease is a chronic autoimmune disease with unknown etiology that can involve different organs. Polymorphisms in Fcγ receptors have been identified as genetic factors in susceptibility to SLE. This study was aimed to investigate effects of two single nucleotide polymorphisms (SNPs) within FcγRIIB and FcγRIIIA genes on systemic lupus erythematous disease activity index (SLEDAI) in an Iranian population. RESULTS: Our findings indicated TT and GG genotypes were the common genotypes of FcγRIIB and FcγRIIIA SNPs in SLE patients, respectively. There were no significant differences in genotype and allele frequencies of FcγRIIB and FcγRIIIA SNPs in SLE and healthy subjects. However, the frequencies of genotypes and alleles of FcγRIIB and FcγRIIIA SNPs were significantly associated with some clinical manifestations used to determine SLEDAI (P < 0.001-0.5).

Early left ventricular remodeling and subclinical cardiac dysfunction in systemic lupus erythematosus: a three-dimensional speckle tracking study.

The article aimed to detect the early cardiac dysfunction in patients with systemic lupus erythematosus (SLE) and predict the relationships between the strain parameters and the disease activities. Three-dimensional speckle-tracking echocardiography was performed to measure left ventricular (LV) structures and global strains on 63 subjects (41 SLE patients with preserved EF and 22 healthy controls). The SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and all the SLE patients were further divided into two subgroups according to disease severity. SLEDAI scores 0-8 were defined as group A, 9-20 were defined as group B. Results indicated that all components of left ventricle global strain [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS)] were significantly reduced in SLE patients. GLS, GRS, GCS had positive correlation with LVEF respectively (r = 0.619, 0.845, 0.91, absolute value, all P < 0.05). The E/e', LVEDVI, LVESVI, LVM, LVMI were increased in all SLE patients (all P < 0.05). In subgroups, GLS and GRS were decreased in group B. Multiple linear regressions analysis indicate that the SLEDAI score was a predictive factor for damage of GLS and GRS. These results indicate that myocardial damage and LV remodeling still occur in SLE patients even with normal EF. The severe disease activity followed with worsening myocardial injury. SLE disease activity might be a potential driver of LV damages.

Association between changes in gene signatures expression and disease activity among patients with systemic lupus erythematosus.

BACKGROUND: We assessed the stability of BAFF, interferon, plasma cell and LDG neutrophil gene expression signatures over time, and whether changes in expression coincided with changes in SLE disease activity. METHODS: Two hundred forty-three patients with SLE were evaluated for disease activity, serological parameters and peripheral blood gene signatures in clinic visits (2 or more per patient) that occurred between 2009 and 2012. Levels of the BAFF gene transcript, plasma cell signature, Interferon (IFN) signature and the low density granulocytes (LDG)-associated neutrophil gene signature were assessed in PAX-gene-preserved peripheral blood by global microarray. The stability of repeated measures of gene expression was quantified using intra-class correlation coefficients. SLE disease activity was measured using the Physicians Global Assessment and the SELENA-SLEDAI index and its components. Using a mixed effects regression model we assessed: 1) the association between a patient's average gene signature expression over time and disease activity, and 2) the association between a patient's changes in gene expression over time and changes in disease activity. RESULTS: Gene expression signatures showed more within-person stability than systolic blood pressure. The IFN signature exhibited the most stability. Patients with high levels of BAFF and IFN transcripts tended to have significantly higher levels of musculoskeletal disease, skin disease, anti-dsDNA, and erythrocyte sedimentation rate, and lower levels of complement. However, changes in BAFF or IFN gene signatures were not associated with changes in disease activity. Similar associations were seen between the LDG gene signature and disease activity. However, when LDG increased, complement tended to increase. Patients with high levels of plasma cell gene signature tended to have higher levels of anti-dsDNA and lower levels of complement. However, unlike the other gene signatures, changes in plasma cell gene signature significantly coincided with changes in anti-dsDNA and complement. CONCLUSIONS: The gene expression signatures were relatively stable within patients over time. BAFF and interferon gene expression were markers of patients with generally higher disease activity, but changes in these gene signatures did not coincide with changes in disease activity. Plasma Cell gene signature expression tracked with the traditional SLE serologic markers of anti-dsDNA and complement.

Trace Elements Associated with Systemic Lupus Erythematosus and Insulin Resistance.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of multifactorial origin. Studies have shown that trace elements such as zinc and copper may help maintain optimum function of the immune system and metabolism, while toxic metals such as lead may increase systemic autoimmunity. The current study aimed to assess the relationship between serum concentration of lithium (Li), vanadium (V), copper (Cu), zinc (Zn), molybdenum (Mo), cadmium (Cd), and lead (Pb) and SLE diagnosis, disease activity measured by SLE disease activity index (SLEDAI) and insulin resistance (IR). This case-control, cross-sectional study included 225 patients, 120 healthy controls, and 105 SLE patients. Serum concentration of Li, V, Cu, Zn, Mo, Cd, and Pb was measured. Serum concentrations of V (p < 0.001), Zn (p < 0.001), and Pb (p < 0.001) were lower and Mo (p < 0.001) and Li (p < 0.001) were higher in patients with SLE compared to healthy controls. SLE diagnosis was associated with higher serum Li (p < 0.001) concentration and lower V (p < 0.001), Zn (p = 0.003), and Pb (p = 0.020). Toxic metals and trace elements were not associated with disease activity. Levels of Cd were higher in patients with IR (p = 0.042). There was no significant association between IR and the other metals. The results indicate that SLE patients have different profiles of trace elements and toxic metals compared to healthy controls. While some toxic metals and trace elements were found to be associated with SLE diagnosis, they had no effect on disease activity and IR.

RasGRP3 in peripheral blood mononuclear cells is associated with disease activity and implicated in the development of systemic lupus erythematosus.

This study examined the relationship between the expression of Ras guanyl nucleotide-releasing protein 3 (RasGRP3) and disease activity in systemic lupus erythematosus (SLE) and explored the possible mechanisms in MRL/lpr mice. We detected the expression of RasGRP3 in peripheral blood mononuclear cells (PBMCs) of SLE patients (n=26) and healthy controls (n=20) by employing RT-PCR and studied the association between the mRNA expression of RasGRP3 in PBMCs and the clinical findings. We also measured the protein level of RasGRP3 in PBMCs by Western blotting (n=10). In addition, we isolated the B cells from PBMCs with magnetic bead separation and determined the RasGRP3 expression by RT-PCR (n=10). Furthermore, we extracted spleen B cells from MRL/lpr mice and knocked down RasGRP3 by siRNA transfection to study the role of RasGRP3 in the pathway of B cell receptor (BCR) activation and the production of pro-inflammatory cytokines. Compared with healthy volunteers, the expression of RasGRP3 was significantly elevated in PBMCs and purified B cells from SLE patients. The mRNA expression of RasGRP3 in PBMCs was positively correlated with SLE disease activity index (SLEDAI). Moreover, silencing RasGRP3 could inhibit Akt and Erk1/2 activation in marginal zone (MZ) and follicular (FO) B cells of MRL/lpr mice. Additionally, the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), was decreased whereas activation of caspase-3 cleavage was induced in vitro. In conclusion, over-expression of RasGRP3 is associated with disease activity and might be involved in the pathogenesis of SLE.

The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.

The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials.

Pattern of systemic lupus erythematosus in Egyptian patients: the impact of disease activity on the quality of life.

INTRODUCTION: Systemic lupus erythematosus (SLE) afflicts young people disproportionately, often at a crucial time in their lives when they are trying to establish relationships, start families and launch careers. As a result, persons with SLE may experience a wide range of physical and psychosocial problems that are not always fully captured by descriptions of the disease's physiological consequences alone. METHODS: In order to characterize the spectrum of the effects of SLE with regards to disease activity and its impact on the quality of life (QoL), a case control study involving 59 SLE Egyptian patients (mean age 28.6 years, 94.9% females) and 20 healthy controls was undertaken. Disease activity was measured by SLE Disease Activity Index (SLEDAI), and quality of life was measured by Short Form-36 health questionnaire (SF-36). RESULTS: Mucocutaneous and hematological manifestations were present in most of the patients and arthralgia in half of them. All domains of SF-36 including general health, physical functions, physical limitations, energy/fatigue, emotional well-being, pain, social functions, and health changes were significantly lower in SLE patients compared to controls. Except for emotional limitations, all domains were correlated with disease activity and low in class IV-V lupus nephritis. CONCLUSION: Physicians should focus on QoL and how to improve it; health education regarding the negative impact of disease activity on the patients should be given attention. The results of QoL studies help physicians to understand and provide better support to SLE patients beside rapid meticulous control of disease activity.