Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus

Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.

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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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Serum levels of soluble programmed cell death protein 1 and soluble programmed cell death protein ligand 2 are increased in systemic lupus erythematosus and associated with the disease activity

Lupus ◽

10.1177/0961203320916517 ◽

2020 ◽

Vol 29 (7) ◽

pp. 686-696

Author(s):

Shinya Hirahara ◽

Yasuhiro Katsumata ◽

Hidenaga Kawasumi ◽

Yashushi Kawaguchi ◽

Masayoshi Harigai

Keyword(s):

Systemic Lupus Erythematosus ◽

Cell Death ◽

Programmed Cell Death ◽

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Dsdna Antibodies ◽

Cell Death Protein

Objective Programmed cell death protein 1 (PD-1) pathway plays important roles in systemic lupus erythematosus (SLE). We aimed to elucidate the association of serum soluble PD-1 (sPD-1) and related molecules with SLE and to explore their usefulness as biomarkers. Methods We retrospectively measured the serum levels of sPD-1, soluble PD-ligand 1 (sPD-L1), soluble PD-ligand 2 (sPD-L2) and interleukin (IL)-21 by ELISA in SLE patients, systemic sclerosis patients and healthy controls. Repeat sera samples were also obtained post treatment. Results The serum levels of sPD-1 and sPD-L2 in SLE patients with high disease activity were significantly higher than those in SLE patients with low disease activity, systemic sclerosis patients and healthy controls ( n = 58, 15, 20 and 21, respectively; p < 0.001). However, the serum levels of sPD-L1 and IL-21 were not elevated in SLE patients. The serum levels of sPD-1 and sPD-L2 were higher among active SLE patients who tested positive for anti-dsDNA antibodies than in those who tested negative ( p = 0.002 and <0.001, respectively). There were moderate correlations between the serum levels of sPD-1 and sPD-L2 and the SLE Disease Activity Index 2000 scores, the titres of anti-dsDNA antibodies and the serum levels of complements. Furthermore, the serum levels of sPD-1 and sPD-L2 decreased significantly in accordance with disease amelioration following treatment ( p < 0.001). Conclusion The present study demonstrated the association of serum sPD-1 and sPD-L2 with SLE and suggests their usefulness as disease activity biomarkers for SLE.

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Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.150486 ◽

2016 ◽

Vol 43 (9) ◽

pp. 1657-1664 ◽

Cited By ~ 5

Author(s):

Claudia Mora ◽

Jorge Medina-Rosas ◽

Ana Maria Santos ◽

Diego A. Jaimes ◽

Ana M. Arbeláez ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Serum Levels ◽

High Avidity ◽

Systemic Lupus ◽

Care Clinic ◽

Dsdna Antibodies

Objective.There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales.Methods.All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured.Results.Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains.Conclusion.R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

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Anti-GAPDH Autoantibody Is Associated with Increased Disease Activity and Intracranial Pressure in Systemic Lupus Erythematosus

Journal of Immunology Research ◽

10.1155/2019/7430780 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Jingjing Sun ◽

Xue Li ◽

Haotian Zhou ◽

Xiaoyun Liu ◽

Jingjing Jia ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Intracranial Pressure ◽

Disease Activity ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Elevated Serum ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Systemic Lupus ◽

Cerebrovascular Lesions

Objective. Systemic lupus erythematosus (SLE) is an immune disease characterized by multiorgan involvement. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating complications of SLE, which lacks efficient diagnostic biomarkers. The recent studies on the anti-GAPDH autoantibodies suggested its potential pathogenic roles in NPSLE. However, the clinical relevance of the anti-GAPDH autoantibodies in patients with SLE is still elusive. In this study, we sought to determine the serum levels of the anti-GAPDH autoantibodies in patients with SLE to investigate the clinical significance of the anti-GAPDH autoantibodies in SLE. Methods. Concentrations of the glyceraldehyde 3-phosphate dehydrogenase autoantibodies (anti-GAPDH autoantibodies) in the serum of 130 SLE patients and 55 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Among the 130 SLE patients, 95 were SLE patients without neuropsychiatric symptoms and 35 had NPSLE. White blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), IgG, IgA, IgM, anti-dsDNA, C3, C4, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF, anti-cardiolipin (Acl), ANA, AnuA, anti-SSA, anti-SSB, β2-GPI, urinalysis, and 24 h urine protein were measured by standard laboratory techniques. Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores were evaluated accordingly. Results. The serum levels of the anti-GAPDH autoantibodies were significantly elevated in the SLE patients, especially in the patients with NPSLE (P=0.0011). Elevated serum anti-GAPDH was correlated with increased SLEDAI-2K (P=0.017), ESR, IgG, and IgM and associated with increased intracranial pressure and incidence of cerebrovascular lesions, but it was protective for seizure disorder incidence. Conclusions. Serum anti-GAPDH autoantibody was increased in both groups of SLE patients with or without neuropsychiatric symptoms and associated with disease severity. It could become an indicator of tissue damages in the brain for the future clinical practice.

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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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Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis

Lupus ◽

10.1177/0961203317707828 ◽

2017 ◽

Vol 26 (13) ◽

pp. 1448-1456 ◽

Cited By ~ 4

Author(s):

K C Maloney ◽

T S Ferguson ◽

H D Stewart ◽

A A Myers ◽

K De Ceulaer

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Renal Biopsy ◽

Diagnostic Criteria ◽

Lupus Erythematosus ◽

Antinuclear Antibodies ◽

Damage Index ◽

Systemic Lupus ◽

Dsdna Antibodies

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0–32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0–9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.

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