scholarly journals Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus

2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Johannes Hartl ◽  
Lee Serpas ◽  
Yueyang Wang ◽  
Ali Rashidfarrokhi ◽  
Oriana A. Perez ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Severity ◽  
Lupus Erythematosus ◽  
Total Plasma ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Free Dna ◽  
Circulating Microparticles ◽  
Associated Proteins

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3-sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis

2018 ◽  
Vol 37 (11) ◽  
pp. 3025-3032 ◽  
Author(s):  
Arwa Mohammad Hassan ◽  
Nessma Mohamed Ahmed Farghal ◽  
Doaa Salah Hegab ◽  
Wesam Salah Mohamed ◽  
Hend Hassan Abd-Elnabi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Severity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Juvenile Systemic Lupus Erythematosus

scholarly journals Comparative analysis of neutrophil gelatinase-associated lipocalin and other laboratory markers for lupus nephritis: a cross-sectional investigation

2016 ◽  
Vol 54 (2) ◽  
pp. 240-245 ◽  
Author(s):  
Sonia L La’ulu ◽  
Brenda B Suh-Lailam ◽  
K Wayne Davis ◽  
Joely A Straseski ◽  
Anne E Tebo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Immunofluorescence Assay ◽  
Igg Antibodies ◽  
Systemic Lupus ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Double Stranded Dna ◽  
Neutrophil Gelatinase

Background Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. This study evaluates the prevalence and correlation between neutrophil gelatinase-associated lipocalin and other biomarkers associated with renal involvement in systemic lupus erythematosus. Methods Paired serum and urine specimens from 50 suspected systemic lupus erythematosus patients, characterized by antinuclear antibodies detected by indirect immunofluorescence assay and varying positive concentrations of anti-double stranded DNA antibodies by Crithidia luciliae immunofluorescence assay, were investigated. Of these 50 patients, 18 were identified with renal involvement based upon laboratory serology. Patients and healthy control serum samples ( n = 50) were also evaluated for high avidity double stranded DNA IgG antibodies, anti-C1q IgG antibodies, and serum creatinine. The prevalence and relationship between biomarkers were evaluated using statistical methods. Results Serum and urine neutrophil gelatinase-associated lipocalin concentrations were significantly elevated in patients compared to controls, with a prevalence of 24% and 36%, respectively. These concentrations were also more markedly increased in systemic lupus erythematosus patients with renal involvement than those without. Spearman’s correlations between neutrophil gelatinase-associated lipocalin and other biomarkers tested ranged from 0.06 to 0.66 in all patients. Combined concordance as determined by Cronbach alpha coefficient between biomarkers was reduced from 0.71 to 0.58 (serum) and 0.62 (urine) when neutrophil gelatinase-associated lipocalin was removed. Conclusions Neutrophil gelatinase-associated lipocalin concentrations are elevated and demonstrate variable associated with other laboratory markers for renal involvement in systemic lupus erythematosus. Prospective longitudinal studies are needed to determine the optimal biomarker combinations for use in routine management of systemic lupus erythematosus patients at-risk for lupus nephritis.

Lack of Association of C-C Chemokine Receptor 5 Δ32 Deletion Status with Rheumatoid Arthritis, Systemic Lupus Erythematosus, Lupus Nephritis, and Disease Severity

2010 ◽  
Vol 37 (11) ◽  
pp. 2226-2231 ◽  
Author(s):  
HENK A. MARTENS ◽  
SACHA GROSS ◽  
GERRIT van der STEEGE ◽  
ELISABETH BROUWER ◽  
JO H.M. BERDEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Severity ◽  
Chemokine Receptor ◽  
Lupus Erythematosus ◽  
Disease Susceptibility ◽  
Systemic Lupus ◽  
Genotype Frequencies ◽  
Chemokine Receptor 5

Objective.C-C chemokine receptor 5 (CCR5) plays an important role in inflammation. A 32 base-pair (Δ32) deletion in the CCR5 gene leads to a nonfunctional receptor. This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases. We investigated whether the Δ32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is associated with disease severity.MethodsDNA samples from 405 RA patients, 97 SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the CCR5 Δ32 deletion. Differences in genotype frequencies were tested between patients and controls. Association of genotypes with disease severity was analyzed.ResultsGenotype frequencies of each group were in Hardy-Weinberg equilibrium. The genotype frequencies of patients did not differ significantly from controls (CCR5/Δ32, Δ32/Δ32: RA 18.3% and 1.2%, respectively; SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there was a trend for lower Δ32 deletion allele frequency in LN patients compared to controls (p = 0.08). There was no significant association between the CCR5 status and disease severity in RA, SLE, or LN.Conclusion.Although an association with LN cannot be excluded, the CCR5 Δ32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect of the Δ32 deletion on disease severity was demonstrated.

scholarly journals Anti-Double-Stranded DNA Isotypes and Anti-C1q Antibody Improve the Diagnostic Specificity of Systemic Lupus Erythematosus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Jia ◽  
Lingling Zhao ◽  
Chunyan Wang ◽  
Jin Shang ◽  
Yi Miao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Specificity ◽  
Systemic Lupus ◽  
Double Stranded Dna

Objectives. We aimed to evaluate the value of immunoglobulin (Ig) G, IgM, and IgA isotypes of anti-double-stranded DNA (anti-dsDNA) and anti-C1q antibody in diagnosing systemic lupus erythematosus (SLE) patients and elucidate their association with disease activity and lupus nephritis. Methods. Blood samples were obtained from 96 SLE patients, 62 other autoimmune disease patients, and 60 healthy blood donors. Anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody were measured by enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to the SLE Disease Activity Index score. Results. When specificity was greater than 90%, the sensitivity of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody in diagnosing SLE was 75%, 45%, 33%, and 49%, respectively. The prevalence of anti-dsDNA IgG (p=0.002), anti-dsDNA IgA (p=0.028), and anti-C1q antibody (p=0.000) in active cases was significantly higher than those in inactive ones. In addition, the presence of anti-C1q antibody was associated with renal involvement (p=0.032). Anti-dsDNA IgM showed no significant association with disease activity, but it was inversely linked with lupus nephritis (p=0.005). When anti-dsDNA IgG and IgA and anti-C1q were combined to evaluate SLE disease activity, the specificity reached the highest level (90%). When anti-C1q positive was accompanied by anti-dsDNA IgM negative, the specificity of diagnosing lupus nephritis was up to 96%. Conclusions. This study demonstrated the role of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody alone or combination in diagnosing SLE. Anti-dsDNA IgG and IgA and anti-C1q were shown to be associated with disease activity, while anti-dsDNA IgM and anti-C1q were associated with lupus nephritis. When the related antibodies were combined, the diagnostic specificity was significantly higher.

Negative Double Stranded DNA and Anti-Smith Antibodies in Lupus Nephritis

2012 ◽  
Vol 4 (2) ◽  
pp. 55-57
Author(s):  
Gagangeet Sandhu ◽  
Anip Bansal ◽  
Aditi Ranade ◽  
Ritu Aggarwal ◽  
Gopal Narayanswami ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Drug Induced ◽  
Serological Screening ◽  
Double Stranded Dna ◽  
Dsdna Antibodies

Systemic lupus erythematosus (SLE) is an autoimmune disease in which auto-antibodies are generated against a variety of intracellular antigens. Anti-Smith (Sm) and anti-double stranded DNA (dsDNA) antibodies in particular are considered to be nephritogenic and their role and correlation with lupus nephritis (LN) has been well established. We present here a case in which the patient had diffuse proliferative full house severe LN, yet negative ds-DNA and anti-Sm antibodies. Although extremely rare, a few subsets of patients with drug-induced LN (hydralazine) have been described in the literature to have negative dsDNA and anti-Sm antibodies on serological screening. Our patient, however, had no evidence of drug induced LN. On further review, and similar to our case, we found only 6 additional well documented cases of non-drug induced severe LN with negative dsDNA antibodies.

Receptor for advanced glycation end products (RAGE) polymorphisms are associated with systemic lupus erythematosus and disease severity in lupus nephritis

Lupus ◽  
2012 ◽  
Vol 21 (9) ◽  
pp. 959-968 ◽  
Author(s):  
HA Martens ◽  
HLA Nienhuis ◽  
S Gross ◽  
G van der Steege ◽  
E Brouwer ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Severity ◽  
Advanced Glycation End Products ◽  
Lupus Erythematosus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Systemic Lupus ◽  
Glycation End Products ◽  
End Products

Objective: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. Methods: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: −429 T/C, −374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. Results: The C allele of −429 T/C, the T allele of −374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE −429 T/C, the A allele of −374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. Conclusion: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.

Systemic lupus erythematosus multiorgan flare with quiescent serologic markers

2021 ◽  
Vol 14 (3) ◽  
pp. e239048
Author(s):  
Jennifer Jane Gile ◽  
Jaskanwal Deep Singh Sara ◽  
Michael R Mueller
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Normal Complement ◽  
Lupus Flare ◽  
Double Stranded Dna ◽  
Serologic Markers ◽  
Heterogeneous Nature ◽  
Degrees Of Severity

Systemic lupus erythematosus (SLE) can affect almost every organ with differing degrees of severity. Typically, SLE activity is associated with hypocomplimentaemia and elevated double-stranded DNA (dsDNA) levels. We describe a case of a severe multiorgan lupus flare including lupus cerebritis, autoimmune haemolytic anaemia, lupus nephritis and lupus myopericarditis with normal complement and dsDNA levels. This highlights the importance of understanding the heterogeneous nature of SLE flares.

scholarly journals Lupus Nephritis in a 2.5 Year Old Girl- An Uncommon Presentation

1970 ◽  
Vol 28 (1) ◽  
pp. 59-62
Author(s):  
H Rahman ◽  
A Begum ◽  
RR Roy ◽  
R Siddique ◽  
K Alam ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Serum Complement ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Serum Complement Level ◽  
Complement Level ◽  
Uncommon Presentation ◽  
Class Iv

Systemic lupus erythematosus (SLE) is very rare and difficult to diagnose before 5 years of age. We are reporting a case of SLE at 2.5- year who presented with recurrent episodes of fever, haematuria , proteinuria and rash . Diagnosis of SLE was confirmed by reduced serum complement level and positive anti double stranded DNA (anti ds DNA). Class IV histological type of Lupus nephritis was evaluated by renal biopsy DOI: 10.3329/jbcps.v28i1.4647 J Bangladesh Coll Phys Surg 2010; 28: 59-62

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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