Leukocyte mitochondrial DNA copy number is a potential non-invasive biomarker for psoriasis

Abstract

Abnormalities in the mitochondria have been linked to psoriasis, a chronic immune-mediated inflammatory skin disease. The mitochondrial DNA (mtDNA) is present in thousands of copies per cell and altered mtDNA copy number (mtDNA-CN), a common indicator of mitochondrial function, has been proposed as a biomarker for several diseases including autoimmune diseases. In this case–control study, we investigated whether the mtDNA-CN is related to psoriasis, correlates with the disease duration and severity, and can serve as a disease biomarker. Relative mtDNA-CN as compared with nuclear DNA was measured by a quantitative real-time polymerase chain reaction in peripheral blood buffy coat samples from 56 patients with psoriasis and 44 healthy controls. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of mtDNA-CN as a biomarker. We found that the mtDNA-CN was significantly decreased in patients with psoriasis compared to healthy controls (93.6±5.3 vs. 205±71; P = 0.04). Sub-group analyses with stratification of patients based on disease duration under or over 10 years and disease severity indicated that the mtDNA-CN was significantly lower in patients with longer disease duration (74±4.3 in disease duration >10 years vs. 79±8.3 in disease duration <10 years, P = 0.009), and higher disease severity (72±4.3 in moderate-to-severe index vs. 88.3 ± 6 in mild index, P = 0.017). Moreover, the mtDNA-CN was negatively correlated with the disease duration and disease severity (r = -0.36, P = 0.006; r = -0.41, P = 0.003 respectively). The ROC analysis of mtDNA-CN showed an area under the curve (AUC) of 0.84 (95% confidence interval: 0.69–0.98; P = 0.002) for differentiating patients from healthy controls. Our study suggests that low mtDNA-CN may be an early abnormality in psoriasis and associates with the disease progression. Our study also suggests that mtDNA-CN may be a novel blood-based biomarker for the early detection of psoriasis.

Comprehensive analysis of mitochondrial DNA variants, mitochondrial DNA copy number and oxidative damage in psoriatic arthritis

“…no. 51304; Qiagen GmbΗ) according to the manufacturer's instructions as previously described ( 24 ). Briefly, a mixture of 200 µl buffy coat, 20 µl protease and 200 µl lysis buffer was incubated at 56˚C for 10 min and then centrifuged at 20,000 x g for 1 min at 4˚C.…”

Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature

“…A 2022 study also found that the mtDNA copy number is a potential biomarker for psoriasis [ 58 ]. In the case–control study, mtDNA copy number was significantly decreased in patients with psoriasis compared to healthy controls.…”

“…Sub-group analysis revealed that mtDNA copy number was significantly lower in patients with a longer psoriasis diagnosis and significantly lower in patients with higher disease severity. The study suggests that mtDNA copy number can be a non-invasive biomarker for early detection of psoriasis [ 58 ].…”

Mitochondria–Melanocyte cellular interactions: An emerging mechanism of vitiligo pathogenesis

“…41 In another study, a low mtDNA copy number was suggested to be utilized as a blood-based biomarker for early psoriasis diagnosis. 42 Therianou at el isolated mtDNA from serum of psoriasis patients, whereas few studies also report that damage to mitochondria could actually benefit these patients. Similarly, in androgenetic alopecia, increased H 2 O 2 enhances TGF-β expression, hair follicle inhibitory factors, senescence and inhibits migration.…”

“…Mitochondrial dysfunction and ROS are reported to be a deciding factor in psoriasis pathogenesis 40 as even demonstrated by Hamanaka et al in his study where TFAM cKO mice were observed with compromised keratinocytes differentiation 41 . In another study, a low mtDNA copy number was suggested to be utilized as a blood‐based biomarker for early psoriasis diagnosis 42 . Therianou at el isolated mtDNA from serum of psoriasis patients, whereas few studies also report that damage to mitochondria could actually benefit these patients.…”