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 Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qingjun Pan ◽  
Linjie Guo ◽  
Jing Wu ◽  
Jun Cai ◽  
Huanjin Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Inflammatory Response ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Clinical Parameters ◽  
Newly Diagnosed ◽  
Systemic Lupus ◽  
Novel Therapeutic

In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P<0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r=0.61,P<0.05;r=0.40,P<0.05; andr=0.54,P<0.05, resp.) and negatively correlated with 24-hour urinary protein (r=0.49,P<0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P<0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r=0.34,P<0.05;r=0.51,P<0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for 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

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients

Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 587-598
Author(s):  
Vinod Umare ◽  
Vandana Pradhan ◽  
Sneha Dadheech ◽  
Anjali Rajadhyaksha ◽  
Kanjaksha Ghosh ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Odds Ratio ◽  
Disease Susceptibility ◽  
Clinical Manifestations ◽  
Interleukin 10 ◽  
P Value ◽  
Promoter Polymorphisms ◽  
Systemic Lupus ◽  
Genotype Frequencies

Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value <0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p < 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p < 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value <0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.

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 &gt;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.

scholarly journals Rapidly progressive lupus nephritis associated with golimumab in a patient with systemic lupus erythematosus and rheumatoid arthritis

Lupus ◽  
2016 ◽  
Vol 26 (4) ◽  
pp. 447-448 ◽  
Author(s):  
Y Saka ◽  
Y Taniguchi ◽  
Y Nagahara ◽  
R Yamashita ◽  
M Karasawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Systemic Lupus

scholarly journals Investigation of rs531564 Polymorphism in the Primary MicroRNA-124 Gene in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: Association with Disease Susceptibility and Clinical Characteristics

2021 ◽  
Author(s):  
Mehdi Hassani ◽  
Mohammad Dehani ◽  
Maryam Zare Rafie ◽  
Emran Esmaeilzadeh ◽  
Saeideh Davar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Control Group ◽  
Systemic Lupus ◽  
Reactive Protein ◽  
Genotype Frequencies ◽  
Dsdna Antibody ◽  
Microrna 124

MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk. In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method. Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001). Our findings propose a considerable association between rs531564 polymorphism in the pri-miR124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.

scholarly journals Chemokines and Chemokine Receptors in the Development of Lupus Nephritis

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Xiaofeng Liao ◽  
Tharshikha Pirapakaran ◽  
Xin M. Luo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Chemokine Receptor ◽  
Lupus Erythematosus ◽  
Chemokine Receptors ◽  
Leukocyte Recruitment ◽  
Systemic Lupus ◽  
Receptor System ◽  
Multiple Organs

Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN.

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.

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