Systemic Lupus Erythematosus Disease Damage Research Articles

Mean Platelet Volume Is Related to Cumulative Disease Damage in Patients with Systemic Lupus Erythematosus.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.

Vascular Endothelial Growth Factor and Its Soluble Receptor in Systemic Lupus Erythematosus Patients.

Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.

IgG1 antibodies against phosphorylcholine are associated with protection in SLE and atherosclerosis: potential underlying mechanisms

Abstract Background The risk of cardiovascular disease (CVD) and atherosclerosis is very high in SLE. This is a clinical problem, and could also shed light on immunity and atherosclerosis in general. IgM antibodies against phosphorylcholine (anti-PC) may be protective in atherosclerosis, cardiovascular disease (CVD) and systemic lupus erythematosus (SLE). We here study IgG1 and IgG2 anti-PC, with focus on atherosclerosis and SLE. Methods We determined anti-PC by ELISA in 116 SLE-patients and 110 age- and sex-matched controls. For functional studies, we used three in-house generated, fully human monoclonal IgG1 anti-PC (A01, D05, E01). Apoptosis was induced in Jurkat T-cells and pre-incubated with A01, D05, E01 or isotype control IgG1 and effects on efferocytosis by human macrophages studied. Anti-PC peptide/protein characterization was determined using a proteomics de novo sequencing approach. Results IgG1 but not IgG2 anti-PC levels were higher among SLE patients (p=0.02). IgG1 anti-PC was negatively associated with SLICC and SLEDAI (OR: 2,978 CI: 0.876–10.098, OR: 5.108 CI 1.3 20.067 respectively) and negatively associated with CVD, atherosclerotic plaques and echolucent (potentially vulnerable plaques) but the association for the two former was not significant after controlling for confounders. D05 had maximum effect on macrophage efferocytosis efficiency, followed by A01 and E01. The monoclonal antibodies showed differential binding specificity to PC and PC associated neo-epitopes. Peptide analysis showed difference in the CDR3 region of the three anti-PC IgG1 clones which are crucial for recognition of PC on apoptotic cell surface and other neo-epitopes. Conclusion Anti-PC IgG1 is negatively associated with disease activity, and disease damage in SLE, but the negative association with CVD is also dependent on confounding risk factors. One potential underlying mechanism could be increased clearance of dead cells. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swedish Heart and Lung Foundation, Reumatikerfonden

Immunoglobulin G1 Antibodies Against Phosphorylcholine Are Associated With Protection in Systemic Lupus Erythematosus and Atherosclerosis: Potential Underlying Mechanisms.

ObjectiveImmunoglobulin M antibodies against phosphorylcholine (anti‐PCs) may be protective in atherosclerosis, cardiovascular disease (CVD), and systemic lupus erythematosus (SLE). We study immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) anti‐PCs, with a focus on atherosclerosis and SLE.MethodsWe determined anti‐PCs by using the enzyme‐linked immunosorbent assay in 116 patients with SLE and 110 age‐ and sex‐matched controls. For functional studies, we used three in‐house–generated, fully human monoclonal IgG1 anti‐PCs (A01, D05, and E01). Apoptosis was induced in Jurkat T cells and preincubated with A01, D05, E01, or IgG1 isotype control, and effects on efferocytosis by human macrophages were studied. Anti‐PC peptide/protein characterization was determined using a proteomics de novo sequencing approach.ResultsIgG1, but not IgG2, anti‐PC levels were higher among patients with SLE (P = 0.02). IgG1 anti‐PCs were negatively associated with Systemic Lupus International Collaborating Clinics (SLICC) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (odds ratio [OR]: 2.978 [confidence interval (CI): 0.876‐10.098] and OR: 5.108 [CI 1.3‐20.067], respectively) and negatively associated with CVD, atherosclerotic plaques, and echolucent plaques (potentially vulnerable plaques), but the association for the two former was not significant after controlling for confounders. D05 had a maximum effect on macrophage efferocytosis efficiency, followed by A01 and E01. The monoclonal antibodies showed differential binding specificity to PC and PC‐associated neoepitopes. A peptide analysis showed a difference in the complementarity‐determining region 3 of the three IgG1 anti‐PC clones that are crucial for recognition of PC on apoptotic cell surfaces and other neoepitopes.ConclusionIgG1 anti‐PCs are negatively associated with disease activity and disease damage in SLE, but the negative association with CVD is also dependent on confounding risk factors. One potential underlying mechanism could be increased clearance of dead cells.

FRI0284 High prolactin levels are independently associated with damage accrual in systemic lupus erythematosus patients.

BackgroundHigh prolactin (PRL) levels have been reported in systemic lupus erythematosus (SLE) patients to be associated with disease activity; they have also been described in patients with chronic diseases like...

SP0139 Predictors for Outcome of Juvenile SLE

Approximately 20% of patients withy systemic lupus erythematosus (SLE) have disease which begins in childhood. Several series have reported that childhood-onset SLE (cSLE) is often more severe than adult disease...

The Prevalence of Low Bone Mineral Density in Brazilian Patients With Systemic Lupus Erythematosus and Its Relationship With the Disease Damage Index and Other Associated Factors

The aim of this study was to examine the prevalence of osteoporosis, osteopenia, and bone mineral density (BMD) less than the expected range based on age in patients with systemic lupus erythematosus (SLE) in a tropical region of Brazil and the relationship between reduced BMD and several associated factors, especially the SLE disease damage index (SDI). We scored 159 patients with creatinine clearance of 60mL/min or more for SDI, which was modified by excluding the osteoporosis item. For postmenopausal women and men older than 50yr, T-scores identified osteopenia (<−1.0 and >−2.5) and osteoporosis (≤−2.5). For all patients, a Z-score of −2.0 or less identified BMD less than the expected range for age. Other variables that influence BMD were studied. The prevalence of osteoporosis, osteopenia, and BMD less than the expected range for age was 28%, 54%, and 29.6%, respectively. The Z-scores were significantly lower in patients with a modified SDI≥1 (mean±standard deviation [SD]=−1.45±1.18) compared with patients with a modified SDI=0 (mean±SD=−0.94±1.01; p=0.01). The lowest Z-score had a significant association with postmenopausal status (p=0.038) and significant correlations with the duration of glucocorticoid (GC) usage (p=0.033, r=−0.17), the cumulative amount of GC (p=0.000, r=−0.28), and parathyroid hormone levels (p=0.003, r=−0.24). A multiple linear regression revealed that the modified SDI (p=0.003) and the cumulative amount of GC (p=0.006) had significant independent associations with the lowest Z-score. In conclusion, a BMD less than the expected range for age occurs frequently in Brazilian patients with SLE independent of the renal failure. The patients with greater SDIs had lower Z-scores, which suggests a direct association between chronic inflammation from disease and a reduced BMD.

Association of N‐terminal pro–brain natriuretic peptide with cardiac disease, but not with vascular disease, in systemic lupus erythematosus

Association of N‐terminal pro–brain natriuretic peptide with cardiac disease, but not with vascular disease, in systemic lupus erythematosus

Brief index of lupus damage: A patient‐reported measure of damage in systemic lupus erythematosus

To develop and test the Brief Index of Lupus Damage (BILD), an interviewer-administered measure of damage in systemic lupus erythematosus (SLE), for use in epidemiologic studies in which administration of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) by trained physicians is not possible or feasible. In addition, we compared the BILD to another recently developed patient-reported measure, the Lupus Damage Index Questionnaire (LDIQ), which was designed as a written survey. A sample of 81 patients from 2 university-affiliated SLE clinics was used to test the criterion validity of the BILD and the LDIQ. A second sample, the Lupus Outcomes Study (n = 728), was used to ascertain the construct validity of the BILD. We found good agreement between most BILD items and corresponding SDI items, and moderately high overall Spearman's rank correlations for SDI with BILD (0.64) and with LDIQ (0.54). BILD scores were higher among older individuals, those with longer disease duration, and those with higher mean disease activity in the preceding 4 years. In addition, higher BILD scores were associated with poorer self-rated health and functional status, greater unemployment and work disability, and increased health care utilization. We developed and performed a preliminary validation study demonstrating content, criterion, and construct validity of a new practical patient-reported instrument of SLE disease damage. Although further studies are needed to examine reliability and to document psychometric properties in other populations, the BILD appears to represent a promising tool for studies of SLE outside the clinical setting.