Beta Cell Function is Disrupted in Patients with Systemic Lupus Erythematosus

Abstract Introduction To investigate how markers of beta cell secretion (proinsulin-processing metabolites) are expressed in systemic lupus erythematosus (SLE) patients and their potential relation to features associated with the disease such as activity or damage. Methods 144 SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analyzed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors. Results Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy (beta coef. 0.19 [95%CI 0.07–0.30], p= 0.002) or not (beta coef. 0.09 [95%CI 0.01–0.17), p= 0.025). Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids (beta coef. 0.08 [95%CI 0.03–0.12], p= 0.001). SLE damage score was associated with higher serum levels of intact (beta coef. 0.51 [95%CI 0.17–0.86] pmol/l, p= 0.004) and split proinsulins (beta coef. 1.65 [95%CI 0.24–3.06] pmol/l, p= 0.022) after multivariable analysis, including disease duration and prednisone use. Conclusion Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.

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Higher Prevalence and Degree of Insulin Resistance in Patients with Rheumatoid Arthritis than in Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.200435 ◽

2020 ◽

pp. jrheum.200435

Author(s):

Juan C. Quevedo-Abeledo ◽

Hiurma Sánchez-Pérez ◽

Beatriz Tejera-Segura ◽

Laura de Armas-Rillo ◽

Soledad Ojeda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Insulin Resistance ◽

Beta Cell ◽

Lupus Erythematosus ◽

Beta Cell Function ◽

Cell Function ◽

Multivariable Analysis ◽

Model Assessment ◽

Systemic Lupus

Objective Since insulin resistance (IR) is highly prevalent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we aimed to determine whether differences in IR between the two conditions exist. Methods Cross-sectional study that encompassed 413 non-diabetic subjects, 186 SLE and 227 RA. Glucose, insulin and C-peptide serum levels, as well as IR by the homeostatic model assessment (HOMA2) were studied. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients with SLE and RA, and also to determine if IR risk factors or disease-related characteristics are differentially associated with IR in both populations. Results The insulin:C-peptide molar ratio was upregulated in RA compared to SLE patients (beta coef. 0.009 [95%CI 0.005-0.014], p=0.000) after multivariable analysis. HOMA2 indexes related to insulin sensitivity were found to be lower (HOMA2-S% beta coef. -27 [95%CI -46- -9], p=0.004) and beta cell function showed higher IR indexes (HOMA2-B% beta coef. 38 [95%CI 23-52], p=0.000) in RA than in SLE patients after multivariable analysis. RA patients more often fulfilled the definition of IR than those with SLE (odds ratio 2.15 [95%CI 1.25-3.69], p=0.005). The size effect of IR factors on IR indexes was found to be equal in both diseases. Conclusion IR sensitivity is lower and beta cell function is higher in RA than in SLE patients. The fact that traditional IR factors have an equal effect on IR in both SLE and RA supports the contention that these differences are related to the diseases themselves.

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Serum Levels of Soluble Fractalkine in Patients with Systemic Lupus Erythematosus

Bulletin of Egyptian Society for Physiological Sciences ◽

10.21608/besps.2013.35098 ◽

2013 ◽

Vol 33 (1) ◽

pp. 73-84 ◽

Cited By ~ 1

Author(s):

Dalia Shaheen ◽

Hisham Habib ◽

Doaa Shahin

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Serum Levels ◽

Systemic Lupus

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FRI0152 PULMONARY HYPERTENSION IN NEWLY DIAGNOSED SPANISH PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM THE RELES COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4906 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 660.2-660

Author(s):

J. Álvarez Troncoso ◽

Á. Robles Marhuenda ◽

F. Mitjavila Villero ◽

F. J. García Hernández ◽

A. Marín Ballvé ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Pulmonary Hypertension ◽

Lupus Erythematosus ◽

Multivariable Analysis ◽

Systolic Pressure ◽

High Morbidity ◽

Inception Cohort ◽

Systemic Lupus ◽

Factors Associated ◽

Pulmonary Arterial

Background:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan involvement. Pulmonary hypertension (PH) is an uncommon manifestation with high morbidity and mortality whose characteristics, prevalence and evolution in SLE are not completely defined.Objectives:Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to to identify the factors associated with pulmonary hypertension (PH) in systemic lupus erythematosus (SLE).Methods:Prospective observational study on a multicenter Spanish inception cohort. Patients with SLE, diagnosed by the American College of Rheumatology (ACR) criteria, since January 2009, who had at least one transthoracic echocardiogram (TTE) performed were selected. Demographic data, diagnostic criteria, follow-ups, treatments and SLEDAI were analyzed.Results:Of 289 patients diagnosed with SLE with TTE performed, 15 (5.2%) patients were identified to have PH. Mean age was 56,9±7,7 years, of which 93,3% (14) were women and 80% (12) Caucasian. The ACR score at diagnosis was 4.66. Mean SLEDAI was 15. Only 5 patients had dyspnea at the time of diagnosis. Mean pulmonary arterial systolic pressure was 49.2±5.6 mmHg. Among the PH, 4 patients had pericarditis (26.6%), 3 (20%) valvulopathies (1 antiphospholipid syndrome), 1 patient pulmonary embolism and 1 shrinking lung. Multivariable analysis indicated that pericarditis (odds ratio (OR)=2.53), and valvulopathies (OR 8.96) were independently associated with the development of PH in SLE. Having PH was associated with older age at diagnosis (p<0.001), more dyspnea (p<0.001), higher ESR (p=0.007), more serositis (p<0.001), higher SLEDAI (p=0.011), higher SLICC (p <0.001), higher number of admissions (p=0.006) and higher mortality (p=0.003).Conclusion:PH in SLE is a serious comorbidity with high mortality. In the RELES cohort it was associated with increased disease activity, pericarditis and valvulopathies. Performing TTE in patients with SLE may favor early diagnosis and treatment.References:[1]Kim JS, Kim D, Joo YB, et al. Factors associated with development and mortality of pulmonary hypertension in systemic lupus erythematosus patients.Lupus. 2018;27(11):1769–1777.[2]Bazan IS, Mensah KA, Rudkovskaia AA, et al. Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.Respir Med. 2018;134:42–46.Disclosure of Interests:Jorge Álvarez Troncoso: None declared, Ángel Robles Marhuenda: None declared, Francesca Mitjavila Villero: None declared, Francisco José García Hernández: None declared, Adela Marín Ballvé: None declared, Antoni Castro Consultant of: Actelion pharmaceuticals, GSK, MSD., Gonzalo Salvador Cervelló: None declared, Eva Fonseca: None declared, Isabel Perales Fraile: None declared, Guillermo Ruiz-Irastorza: None declared

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Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-021-87024-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Danielle Perez-Bercoff ◽

Hélène Laude ◽

Morgane Lemaire ◽

Oliver Hunewald ◽

Valérie Thiers ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cell Death ◽

Lupus Erythematosus ◽

Immunosuppressive Treatment ◽

Elevated Serum ◽

Serum Levels ◽

Chronic Inflammatory Disease ◽

Mrna Levels ◽

Systemic Lupus ◽

Inflammatory Conditions

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.

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Serum levels and gene polymorphisms of angiopoietin 2 in systemic lupus erythematosus patients

Scientific Reports ◽

10.1038/s41598-020-79544-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jia-Min Wang ◽

Wang-Dong Xu ◽

Zhi-Chao Yuan ◽

Qian Wu ◽

Jie Zhou ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Gene Polymorphisms ◽

Serum Levels ◽

Healthy Individuals ◽

Systemic Lupus ◽

Potential Biomarker ◽

Angiopoietin 2 ◽

Inflammatory Autoimmune Diseases

AbstractThis study aimed to discuss association between serum Angiopoietin2 (Ang2) levels, Ang2 gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility. It was carried out by 235 SLE, 342 other inflammatory autoimmune diseases patients and 380 healthy individuals. Serum Ang2 levels was examinated by ELISA, and Ang2 rs12674822, rs1823375, rs1868554, rs2442598, rs3739390 and rs734701 polymorphisms were genotyped using KASP. Increased Ang2 concentrations in SLE patients were observed compared with healthy controls and patients with other inflammatory autoimmune diseases. For allelic contrast, except for rs1823375 (P = 0.058) and rs2442598 (P = 0.523), frequencies of alleles for other polymorphisms were significantly different between SLE patients and controls. Genotypes for rs12674822 (TT), rs1868554 (TT, TA and TT+TA), rs734701 (TT) were negatively correlated with SLE susceptibility (OR = 0.564 for rs12674822; OR = 0.572, OR = 0.625, OR = 0.607 for rs1868554; OR = 0.580 for rs734701). Patients carrying rs1868554 T allele and rs3739390 G allele were more likely to develop hematuria (P = 0.039; P = 0.003). The G allele frequencies of rs12674822 and rs2442598 were higher in SLE patients with proteinuria (P = 0.043; P = 0.043). GC genotype frequency of rs3739390 was higher in patients with ds-DNA (+) (P = 0.024). In summary, SLE had increased serum Ang2, which may be a potential biomarker, and the polymorphisms correlated with SLE.

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Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Mediators of Inflammation ◽

10.1155/2015/328078 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Conti Fabrizio ◽

Ceccarelli Fulvia ◽

Perricone Carlo ◽

Massaro Laura ◽

Marocchi Elisa ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Renal Involvement ◽

Serum Levels ◽

Activity Measurement ◽

Systemic Lupus ◽

Before And After ◽

Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

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