Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

Abdelal, Ibrahim Tharwat; Zakaria, Mohammad A; Sharaf, Doaa M.; El-Akad, Ghada M

doi:10.1016/j.ejr.2016.06.005

Cited by 22 publications

(29 citation statements)

References 33 publications

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“…In this study, we found the expression of CXCR4, CCR7, CD83, 86 and IFN-α were up-regulated in RA serum-stimulated DCs and this effect was inhibited by HCQ, indicating that some substances in RA serum induced DC activation were blocked by HCQ. As TLR9 is a cytosolic DNA sensor, we hypothesized cell-free DNA in serum of RA patients, which is largely attributed to the excessive DNA released by numerous dead cells or incomplete clearance of apoptotic cells [ 35 , 36 ], enters into the cytoplasm when binding to antimicrobial peptide LL37, auto-antibodies or HMGB1 and triggers TLR9 and then induces activation of DCs in patient [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

The mechanisms of hydroxychloroquine in rheumatoid arthritis treatment: Inhibition of dendritic cell functions via Toll like receptor 9 signaling

Han¹,

Li²,

He³

et al. 2020

Biomedicine & Pharmacotherapy

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Graphical abstract DCs act as sentinels for the immune system. DCs capture antigens locally and become mature, characterized by up-regulation of chemokine receptors (CCR7 and CXCR4), adhesion molecule (L-selectin), co-stimulator molecules (CD40, CD80 and CD86) and MHC II. Under high concentration of CCL21 in draining lymph nodes (LNs), mature DCs traffic to LNs via afferent lymph vessels and present antigens to T cells, resulting in the development of arthritis. HCQ impaires DC maturation via blocking TLR9 signaling, retrains DC migration to LNs, and prevents the initiation and progression of RA.

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Section: Discussionmentioning

confidence: 99%

The mechanisms of hydroxychloroquine in rheumatoid arthritis treatment: Inhibition of dendritic cell functions via Toll like receptor 9 signaling

Han¹,

Li²,

He³

et al. 2020

Biomedicine & Pharmacotherapy

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“…14 In Egyptian SLE patients, cell-free DNA, but not anti-dsDNA, correlated with disease activity. 35…”

Section: Discussionmentioning

confidence: 99%

Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to disease manifestations, damage and antiphospholipid antibodies

Gheita

Abaza

Hammam

et al. 2018

Lupus

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Background Attempts are ongoing to unveil unresolved queries about anti-double-stranded deoxyribonucleic acid (anti-dsDNA), their precise pathogenic effects and to what extent blocking them would be a useful therapeutic goal. Objectives The aim of the present study was to determine the anti-dsDNA antibodies titre in systemic lupus erythematosus (SLE) patients and investigate their relation to the disease characteristics, activity, damage and antiphospholipid autoantibodies (aPL). Methods Seventy female SLE patients and 35 age- and sex-matched controls were included. The anti-dsDNA level and aPL were measured. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) were assessed. Results The mean age of the patients was 27.5 ± 5.1 years, disease duration 7.7 ± 5.4 years, and SLEDAI and SLICC/ACR-DI scores were 6.8 ± 8.04 and 1.2 ± 1.3, respectively. Anti-dsDNA was positive in 61.4% of the patients and the titre (133.2 ± 100.5 IU/ml) was significantly higher compared to controls (22.03 ± 17.2 IU/ml) ( p < 0.0001). The anti-dsDNA level was significantly increased in those with musculoskeletal manifestations ( p = 0.007) and positive anti-β2 glycoprotein (anti-β2GP) ( p = 0.037) and decreased in those with neuropsychiatric manifestations ( p = 0.004) and those receiving cyclophosphamide (CYC) ( p = 0.013). The anti-dsDNA level tended to be higher in active patients. The anti-dsDNA titre significantly correlated with the erythrocyte sedimentation rate ( p = 0.001), anticardiolipin IgG and IgA antibodies ( p = 0.008) and anti-β2GP IgG ( p = 0.03) and IgA ( p = 0.002) and inversely with the total leucocytic count ( p < 0.0001) and SLICC/ACR-DI ( p = 0.001). Conclusion Anti-dsDNA is remarkably increased in SLE patients especially those with musculoskeletal manifestations and aPL. A protective role seems likely in those with neuropsychiatric manifestations and those receiving CYC and may form a shield against disease tissue damage.

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“…Once neutrophils expel the NETs, NETs can be found in the plasma as cf-dsDNA [ 38 , 39 ]. Interestingly, while NET formation is thought to be beneficial to wound health by sequestering and destroying pathogens [ 17 , 22 ], at the same time it has been demonstrated to slow the process of wound healing [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, however, we observed no correlation between plasma cf-dsDNA and obesity or insulin resistance in total joint arthroplasty subjects. Notably, while the assessment of cf-dsDNA is objective and quantitative [ 40 ], it is not specific, and can be increased in a variety of conditions including cancer [ 38 ], systemic lupus erythemus [ 39 ] and rheumatoid arthritis [ 39 ], and even independent of NET formation [ 41 ]. Although we account for many of these conditions in our study’s exclusion criteria, since cf-dsDNA can be present independent of NET formation whether there is any correlation between the measured NETs and HOMA-IR or BMI remains unanswered.…”

Section: Discussionmentioning

confidence: 99%

Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report

et al. 2021

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While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.

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Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

Cited by 22 publications

References 33 publications

The mechanisms of hydroxychloroquine in rheumatoid arthritis treatment: Inhibition of dendritic cell functions via Toll like receptor 9 signaling

The mechanisms of hydroxychloroquine in rheumatoid arthritis treatment: Inhibition of dendritic cell functions via Toll like receptor 9 signaling

Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to disease manifestations, damage and antiphospholipid antibodies

Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report

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