Review Article

DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

Table 1

Evidence of increased DNA damage in systemic lupus erythematosus.

Type of sample/originStudy groupsMethodological strategyMain findingsReference

(i) Urine
(ii) Venous blood
(iii) Peripheral blood mononuclear cells
(i) SLE patients
(ii) RA patients
(iii) Healthy individuals
(i) Determination of 8-oxodG levels in urine and DNA of immune complexes.
(ii) Quantification of DNA base products in monocytes under oxidative stress (H2O2) and irradiated with UV
(i) 8-oxodG levels were 103 times lower in urine and higher in DNA associated with circulating immune complexes (plasma) in SLE patients (0.38–3.6 pmol 8-oxodG/mg DNA) compared to patients with RA and healthy subjects.
(ii) In response to H202, SLE cells showed a rapid conversion of dG to 8-oxodG as well as cells from healthy individuals. However, the rate of removal of the damaged base and viability decreased in SLE cells ().
[4, 35]

(i) Peripheral blood mononuclear cells(i) SLE patients
(ii) Patients with SLE and aggregated CVD (cases)
(iii) Patients with SLE without aggregated CVD (controls)
(iv) Healthy individuals
(i) Comet assay.
(ii) Determination of MDA level
(iii) Determination of SOD activity
(i) Increased DNA damage in SLE patients cells compared to healthy individuals
(ii) Plasma increase of MDA in SLE patients compared to healthy subjects ()
(iii) Decrease of SOD activity in SLE patients compared to healthy individuals ()
(iv) Less SOD activity in cases with SLE compared to SLE control patients
[69]

(i) Freshly isolated neutrophils
(ii) Cultured neutrophils
(i) SLE patients
(ii) RA patients
(iii) Healthy individuals
(i) Comet assay
(ii) Apoptosis evaluation by binding to Annexin V and cell morphology
(iii) Repair rates of oxidative DNA damage by formamidopyrimidine DNA glycosylase incorporation in the comet assay
(i) Greater damage in nuclear DNA in neutrophils isolated and cultured from SLE patients ( and 27.3%, resp.) compared to RA patients (, , and 19.3%, , resp.) and healthy individuals (, , and 18.7%, , resp.).
(ii) Higher levels of circulating apoptotic neutrophils in SLE patients compared to RA patients and healthy individuals
(iii) Altered ability to repair oxidized DNA in neutrophils in 3 of 5 patients with SLE
[66]

(i) Peripheral blood mononuclear cells(i) SLE patients
(ii) Healthy individuals
(i) Determination of DNA damage and induction of apoptosis in PBMCs exposed to melphalan and cisplatin by quantifying H2AX foci by immunofluorescence and comet assay(i) Increase in intrinsic DNA damage in SLE patients’ cells compared to healthy individuals’ cells (Olive Tail Moment units of 15.8 ± 2.3 versus 3.0 ± 1.4 in comet assay )
(ii) Lower doses of melphalan and cisplatin (9.9 ± 4.8 or 29.8 ± 8.3 μg/ml, resp.) are required to cause apoptosis in SLE cells compared to control cells (32.3 ± 7.7 or 67.7 ± 5.5 μg/ml, resp.)
(iii) Greater double-strand DNA breaks in SLE patients’ cells than in healthy individuals’ cells ()
(iv) In SLE patients, double-stranded DNA levels correlated with apoptosis levels ().
[127]

(i) Peripheral blood mononuclear cells(i) SLE patients
(ii) Healthy individuals
(i) Determination of oxidative lesions in mtDNA by PCR.(i) Higher levels of mtDNA damage in SLE patients compared to healthy individuals (0.41 lesions/10 kb/string versus 0.10 lesions/10 kb/strand; ).
(ii) SLE patients without major organ affection showed a 20% increase in mtDNA injury levels compared to healthy controls (0.489 lesions versus 0.101; ).
(iii) SLE patients with major organ affection showed a tendency to have lower levels of mtDNA.
(iv) The disease degree damage correlated negatively with mtDNA levels ().
(v) The number of mtDNA lesions correlated positively with the duration of the disease ().
[70]

DNA: deoxyribonucleic acid; mtDNA: mitochondrial DNA; RA: rheumatoid arthritis; PBMC: peripheral blood mononuclear cells; CVD: cardiovascular disease; SLE: systemic lupus erythematosus; MDA: malondialdehyde; PCR: polymerase chain reaction; UV: ultraviolet radiation; SOD: superoxide dismutase; 8-oxodG: 8-hydroxy-2-deoxyguanosine.