Elevated soluble intercellular adhesion molecule-1 levels in patients with systemic lupus erythematosus: relation to insulin resistance

OBJECTIVE: Intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin supergene family and play a central role in cell-to-cell and in cell-to-extracellular matrix-mediated immune responses. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variety of immunological abnormalities. The relationship between soluble adhesion molecules and insulin resistance has been observed in different populations. However, the association of circulating levels of soluble cell adhesion molecules with insulin resistance and/or hyperinsulinemia in patients with SLE has not been extensively established. METHODS: We evaluated the relationship of soluble ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) to insulin resistance in 68 patients with SLE and 34 age-matched healthy controls. RESULTS: Patients with SLE had significantly higher fasting insulin levels, homeostasis model assessment insulin resistance (HOMA-IR), HOMA beta-cell, and plasma levels of sICAM-1 and sVCAM-1 than controls. SLE patients with HOMA-IR in the top quartile had the highest plasma levels of sICAM-1. However, there was no statistical difference in plasma levels of sVCAM-1 between patients in the respective quartiles of insulin sensitivity-related variables. Plasma levels of sICAM-1, but not sVCAM-1, were significantly correlated with fasting insulin (r = 0.327, p = 0.006), HOMA-IR (r = 0.278, p = 0.022), and HOMA beta-cell (r = 0.359, p = 0.003). In addition, fasting insulin was responsible for sICAM-1 variability in patients with SLE. CONCLUSION: The elevation of plasma levels of sICAM-1 was associated with a status of insulin resistance in patients with SLE.     

Serum L-ficolin levels in patients with systemic lupus erythematosus

Objective

L-ficolin plays an important role in innate immunity and is involved in apoptosis. The objective of this study was to investigate the relationship between serum L-ficolin levels and clinical manifestations in patients with systemic lupus erythematosus (SLE).

Methods

Serum L-ficolin levels were determined by enzyme-linked immunosorbent assay in 66 SLE patients and 50 healthy controls.

Results

Median serum L-ficolin levels were 5.0 and 8.7?μg/ml in SLE patients and controls, respectively (p?=?0.0001). There were no significant differences in serum L-ficolin levels between the active disease group [SLE Disease Activity Index (SLEDAI) >6] and the inactive disease group (SLEDAI <5). Decreased serum L-ficolin levels were associated with thrombocytopenia (median of with vs. without thrombocytopenia 3.4 vs. 5.3?μg/ml, p?=?0.008). There were no correlations between serum L-ficolin levels and SLEDAI, serum C3, or serum C4 levels.

Conclusion

The association between L-ficolin and thrombocytopenia suggests a pathogenic role for L-ficolin in thrombocytopenia in SLE.     

Altered coronary vasomotor function in young patients with systemic lupus erythematosus

OBJECTIVE: Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. METHODS: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. RESULTS: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION: These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.     

Serum L-ficolin levels in patients with systemic lupus erythematosus

Abstract

Objective L-ficolin plays an important role in innate immunity and is involved in apoptosis. The objective of this study was to investigate the relationship between serum L-ficolin levels and clinical manifestations in patients with systemic lupus erythematosus (SLE).

Methods Serum L-ficolin levels were determined by enzyme-linked immunosorbent assay in 66 SLE patients and 50 healthy controls.

Results Median serum L-ficolin levels were 5.0 and 8.7 μg/ml in SLE patients and controls, respectively (p = 0.0001). There were no significant differences in serum L-ficolin levels between the active disease group [SLE Disease Activity Index (SLEDAI) > 6] and the inactive disease group (SLEDAI < 5). Decreased serum L-ficolin levels were associated with thrombocytopenia (median of with vs. without thrombocytopenia 3.4 vs. 5.3 μg/ml, p = 0.008). There were no correlations between serum L-ficolin levels and SLEDAI, serum C3, or serum C4 levels.

Conclusion The association between L-ficolin and thrombocytopenia suggests a pathogenic role for L-ficolin in thrombocytopenia in SLE.     

Serum interferon levels in patients with systemic lupus erythematosus

Levels of interferon (IFN) were measured in 81 serum samples from 23 patients with systemic lupus erythematosus (SLE) by a plaque-reduction method and correlated retrospectively with clinical records of disease activity, anti-DNA binding, and serum complement measurements. IFN titers were found to correlate with both clinical disease activity and anti-DNA binding, but no relation was found to serum complement. Most (76.6%, 31 of 41) serum samples obtained during periods of active disease contained measureable amounts of IFN, but only 9.1% (2 of 22) of results of tests on samples obtained during periods of disease quiescence were positive (P less than 0.005). Of samples with clearly elevated anti-DNA binding (greater than 40%), 69.7% (23 of 33) had positive results for IFN, but 57.1% (8 of 14) had negative results when the anti-DNA binding was normal (less than 20%) (P less than 0.005). Measurement of serum IFN titers in patients with SLE, therefore, provides another serologic marker of disease activity. Contrary to the findings of previous studies, the IFN found in the present study was characterized as IFN-alpha, or Type I IFN, on the basis of acid stability and neutralization by antibody to IFN-alpha. Of interest are the questions raised about the origin of IFN in the sera of patients with SLE and what role IFN might have in the pathogenesis of the autoimmune disease in view of the many documented immunomodulating effects of IFN.     

Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydroxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metabolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P less than 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.     

High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus

OBJECTIVE: To examine low-density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE). METHODS: Fifty-nine SLE patients and 59 healthy, age-matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A-I, and fatty acids were also measured. RESULTS: Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high-density lipoprotein cholesterol (HDL-C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL-C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels. CONCLUSION: SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.     

Type B insulin resistance in a systemic lupus erythematosus patient

In type B insulin resistance and acanthosis nigricans, the insulin resistance is due to the presence of anti‐insulin receptor antibody 1. Approximately one‐third of patients with these antibodies have an associated illness such as systemic lupus erythematosus (SLE) or Sjögren's syndrome. This report describes a case wherein the patient had presented with uncontrolled diabetes and required > 3000 units of human insulin to control hyperglycemia. She also had features of SLE. There was complete recovery following treatment with steroids.     

Metabolic syndrome and insulin resistance comorbidity in systemic lupus erythematosus

Objective

The aim of the present study was to assess the effect of metabolic syndrome (MetS) and insulin resistance comorbidity on the carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE) patients and their relationship to clinical manifestations, disease activity, and damage.

Methods

The study included 92 SLE patients (mean age 30.18?±?8.27 years) and 30 matched controls. Disease activity and damage were assessed by the SLEDAI and SLICC indices, respectively. The Health Assessment Questionnaire II (HAQII) and Quality of Life (QoL) index were evaluated in the patients. Levels of insulin, glucose, and creatinine and the lipid profile were measured in patients and controls. Insulin sensitivity was estimated using the homeostatic model assessment index (HOMA-B) for beta cell function and (HOMA-IR) for peripheral tissue insulin resistance. The carotid IMT was measured by ultrasonography.

Results

The SLE patients had high HOMA-IR and HOMA-B. The IMT was significantly increased (0.82±?0.29 mm) compared to the controls (0.45±?0.2 mm).The HOMA-IR, SLEDAI, SLICC, HAQII, and IMT were significantly higher and the QoL lower in those with MetS (n?=?34) compared to those without (n?=?58), while the HOMAB was comparable. There was a significant correlation between the IMT and the SLEDAI, SLICC, and WHR.

Conclusion

Insulin sensitivity and IMT are altered in SLE patients, especially those with MetS comorbidity with an associated increase in disease activity and damage. Effective management of MetS would help control SLE activity, damage, and the future development of cardiovascular events especially in the absence of symptoms of cardiovascular disease.     

Platelet bound IgG levels in patients with systemic lupus erythematosus

Platelet bound IgG (PBIgG) measured by antiglobulin consumption assay was compared with indices of clinical and laboratory disease activity in 37 nonthrombocytopenic patients with systemic lupus erythematosus. There was no correlation with clinical disease activity. When patients with a PBIgG level over 50 ng/10(7) platelets were compared to those with normal PBIgG levels (less than 20 ng/10(7) platelets), however, they had a significantly higher DNA binding level (p less than 0.05). In 17 patients there was no correlation between PBIgG levels and circulating immune complexes as measured by the Raji cell assay. Ten patients with PBIgG levels over 50 ng/10(7) platelets were followed for a mean of 23 months (5-26 months). None developed thrombocytopenia.     

Raised serum APRIL levels in patients with systemic lupus erythematosus

OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both. METHODS: Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.     

Elevated apolipoprotein-B levels in corticosteroid-treated patients with systemic lupus erythematosus

Patients treated with corticosteroids often have a dyslipoproteinemia characterized by elevated plasma levels of triglyceride and low density lipoprotein cholesterol and/or decreased levels of the high density lipoprotein2 fraction of high density lipoprotein cholesterol. This study was undertaken to determine if such patients also have elevated apolipoprotein-B (apoB) levels and/or abnormalities of the activities of the triglyceride lipases in postheparin plasma. Plasma lipoprotein levels and the postheparin activities of hepatic lipase and lipoprotein lipase were measured in 28 women with systemic lupus erythematosus (SLE) who were treated with prednisone, 10 women with SLE not treated with prednisone, and 15 normal women. The prednisone-treated group had higher mean plasma levels of triglyceride [2.06 +/- 1.3 (+/- SD) vs. 1.15 +/- 0.35 and 0.95 +/- 0.46 mmol/L; P less than 0.01], low density lipoprotein cholesterol [3.41 +/- 1.4 (+/- SD) vs. 2.79 +/- 0.67 and 2.84 +/- 0.70 mmol/L; P less than 0.01], and apoB [1.16 +/- 0.35 (+/- SD) vs. 0.82 +/- 0.13 and 0.76 +/- 0.22 g/L] than the other 2 groups. Forty-three percent of the prednisone-treated group had apoB levels of 1.20 g/L or more compared to 7% of normal subjects and none of the untreated SLE group (P less than 0.05). However, of the 12 prednisone-treated patients with elevated plasma apoB levels 5 had normal plasma lipid levels. There were no differences in the postheparin lipase activities among the 3 groups. These data indicate that corticosteroid-treated patients have elevations in apoB as well as hyperlipidemia. The lipoprotein abnormalities may explain the increased risk of atherosclerosis reported in these patients.     

Elevation of plasma interleukin-18 concentration is associated with insulin levels in patients with systemic lupus erythematosus

We previously reported that systemic lupus erythematosus (SLE) patients have a higher risk of insulin resistance and abnormal insulin secretion. Recent studies demonstrated that interleukin (IL)-18, a novel pro-inflammatory cytokine, may be involved in triggering the inflammatory processes in SLE and the concentrations of circulating IL-18 in SLE patients were significantly higher than those in healthy subjects. IL-12 has a synergistic effect with IL-18, and both cytokines are inducers of interferon (IFN)-gamma. The objective of this study was to identify the effect of fasting insulin levels on circulating concentrations of IL-18, IL-12 and IFN-gamma in patients with SLE. Plasma levels of proinflammatory Th-1 cytokines were determined by enzyme-linked immunosorbent assay in a total of 70 female SLE patients and 34 age-matched healthy females. Insulin resistance (IR) and secretion were evaluated by homeostasis model assessment (HOMA). All patients were further classified into subgroups based on the quartiles of fasting insulin levels. SLE patients with fasting insulin levels in the top quartile compared with other quartiles had significantly higher plasma levels of IL-18. The presence of insulin auto-antibodies (IAA) in SLE patients had no influence on plasma levels of IL-18. In addition, fasting insulin levels and HOMA IR were positively correlated with IL-18 in all SLE patients, respectively. In conclusion, elevated circulating IL-18 concentrations corresponded with increases in fasting insulin levels and the status of insulin resistance in patients with SLE.     

IgG subclass serum levels in systemic lupus erythematosus patients

IgG subclass levels of sera from 105 patients with systemic lupus erythematosus (SLE) were determined by immunonephelometric assay. Patients were divided into two groups according to clinical activity of the disease: active disease and remission. Forty-five normal controls were also measured. We found a significant increase of IgG1 (p = 0.000), IgG2 (p = 0.000), and IgG3 (p = 0.000) in SLE sera, while IgG4 (p = 0.494) values did not differ significantly from those of controls. When patients were divided according to clinical activity, decrease of IgG3 concentration was observed in the patients in remission. In contrast, the concentrations of IgG1, IgG2, and IgG4 subclass were similar between the two groups (p > 0.05). Our data suggest that differential increase of IgG subclasses during the course of SLE may be of relevance to the pathogenesis of the disease.     

Altered frequencies of memory B cells in new-onset systemic lupus erythematosus patients

Clinical Rheumatology - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, characterized by B cell hyperactivity and pathogenic autoantibodies formation. The objective of...     

Clinical significance of plasma presepsin levels in patients with systemic lupus erythematosus

Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE.

Methods: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels.

Results: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p?=?.0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r =?–0.4454, p =?.0430), CH50 (r =?–0.4502, p =?.0406) and positively with SLEDAI-2K (r =?0.4801, p =?.0237).

Conclusion: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.