Background: Mitochondrial ATP Synthase 6 (MT-ATP6), a subunit of mitochondrial ATP synthase, is essential for cellular energy production and serves as a marker of mitochondrial dysfunction. Although mitochondrial dysfunction has been implicated in autoimmune diseases, its role in ANCA-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) remains unclear. This study investigates serum MT-ATP6 levels in AAV and IgG4-RD patients and examines their relationship with disease activity and clinical parameters.
Objectives: To evaluate serum MT-ATP6 levels in AAV and IgG4-RD patients compared to healthy controls and to analyze their association with disease activity, clinical features, and laboratory markers.
Methods: This retrospective study included 37 AAV patients, 21 IgG4-RD patients, and 21 healthy controls. Serum MT-ATP6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) for AAV and the IgG4-Related Disease Responder Index (IgG4-RI) for IgG4-RD. Clinical parameters included constitutional symptoms, renal and pulmonary involvement, while laboratory data included CRP, hemoglobin, and creatinine levels. Diagnostic performance was evaluated using ROC curve analysis.
Results: Baseline characteristics are summarized in Tables 1 and 2. Serum MT-ATP6 levels were significantly lower in AAV (median: 155.0 ng/L, IQR: 130.2–188.6) and IgG4-RD (median: 156.2 ng/L, IQR: 133.4–174.6) patients compared to healthy controls (median: 223.3 ng/L, IQR: 148.2–1237.0; p = 0.013). No significant differences were observed between AAV and IgG4-RD patients. MT-ATP6 levels showed no significant correlation with disease activity (BVAS or IgG4-RI), demographic factors, clinical features, or laboratory markers. ROC analysis demonstrated moderate diagnostic accuracy, with AUC values of 0.722 (p = 0.005) for AAV and 0.711 (p = 0.019) for IgG4-RD.
Conclusion: Patients with AAV and IgG4-RD exhibit reduced MT-ATP6 levels, indicating mitochondrial dysfunction independent of disease activity. MT-ATP6 demonstrates moderate diagnostic potential; however, further longitudinal studies are required to validate its clinical utility and explore its role in the pathogenesis and management of autoimmune diseases.
REFERENCES: NIL.
Characteristics of ANCA-associated vasculitis patients.
Diagnosis, n (%) | AAV (n=37) | ||
---|---|---|---|
GPA | 28 (75.7) | ||
EGPA | 6 (16.2) | ||
MPA | 3 (8.1) | ||
Gender , n (%) | |||
Female | 15 (40.5) | ||
Male | 22 (59.5) | ||
Age at diagnosis , mean ± SD (min-max) | 50.0 ± 12.3 (22-74) | ||
Exitus , n (%) | 3 (8.1) | ||
Follow-up duration , months, median (IQR) | 52.3 (11.2-109.7) | ||
Active disease , n (%) | 11 (29.7) | ||
Clinical , n (%) | |||
Constitutional | 5 (13.5) | ||
Cutaneous | 2 (5.4) | ||
Mucosal/Ocular | 5 (13.5) | ||
ENT | 8 (21.6) | ||
Pulmonary | 6 (16.2) | ||
Cardiac | 1 (2.7) | ||
Abdominal | 1 (2.7) | ||
Renal | 7 (18.9) | ||
Nervous System | 1 (2.7) | ||
Active (n=11) | Inactive (n=26) | P | |
BVAS , median (IQR) | 19 (12-24) | 0 (0) | <0.001 |
Laboratory | |||
CRP, mg/L, median (IQR) | 83.1 (13.7-100.0) | 3.35 (3.3-8.2) | <0.001 |
Hb, g/dL, mean ± SD | 10.1 ± 2.2 | 13.4 ± 2.4 | <0.001 |
WBC, 10³/mcL, median (IQR) | 10.4 (7.0-12.0) | 7.5 (6.4-9.5) | 0.065 |
NLR, median (IQR) | 6.6 (3.75-8.5) | 2.7 (2.2-3.75) | 0.001 |
SII, median (IQR) | 1991 (1106-3492) | 678 (522-1123) | 0.001 |
SIRI, median (IQR) | 2.96 (1.56-3.40) | 1.56 (1.23-2.97) | 0.087 |
Ferritin, mcg/L, median (IQR) | 223 (111.5-843.5) | 55.6 (24.1-93.4) | 0.043 |
Albumin, mg/dL, median (IQR) | 3.6 (3.1-3.9) | 4.6 (4.275-4.8) | <0.001 |
Creatinine, mg/dL, median (IQR) | 1.82 (1.22-2.92) | 0.95 (0.76-1.36) | 0.040 |
eGFR, mL/min/1.73 m², median (IQR) | 40 (23-62) | 84.5 (58.5-98.25) | 0.051 |
Proteinuria, mg/day, median (IQR) | 313 (175-1402) | 157 (108-322) | 0.034 |
MT-ATP6, ng/L, median (IQR) | 152.3 (126.5-201.7) | 160.1 (148.6-171.2) | 0.761 |
Characteristics of IgG4-related disease patients.
IgG4-RD (n=21) | |||
---|---|---|---|
Gender , n (%) | |||
Female | 10 (47.6) | ||
Male | 11 (52.4) | ||
Phenotype , n (%) | |||
Pancreatic-biliary-hepatic | 1 (4.8) | ||
RPF-aortitis | 9 (42.9) | ||
Head and neck limited | 5 (23.8) | ||
Mikulicz-systemic | 3 (14.3) | ||
Other | 3 (14.3) | ||
Age at diagnosis , mean ± SD (min-max) | 51.2 ± 14.2 (20-71) | ||
Follow-up duration , months, median (IQR) | 14.0 (0.1-65.0) | ||
Exitus , n (%) | 1 (4.8) | ||
Active disease , n (%) | 10 (47.6) | ||
IgG4-RD responder index | |||
Activity, median (IQR) | 3 (3-4) | ||
Damage, median (IQR) | 0 (0-0.5) | ||
Active (n=10) | Inactive (n=11) | P | |
IgG4-RD RI activity , median (IQR) | 3 (3-4) | 0 (0) | <0.001 |
Laboratory | |||
CRP, mg/L, median (IQR) | 9.6 (3.9-32.2) | 3.3 (2.85-3.7) | 0.005 |
Hb, g/dL, mean ± SD | 13.2 ± 2.3 | 13.8 ± 1.6 | 0.493 |
WBC, 10³/mcL, median (IQR) | 7.6 (6.7-9.5) | 6.9 (6.0-7.9) | 0.282 |
NLR, median (IQR) | 2.2 (1.2-4.6) | 2.0 (1.7-2.2) | 0.512 |
SII, median (IQR) | 703 (491-1558) | 509 (395-594) | 0.114 |
SIRI, median (IQR) | 1.21 (0.85-3.94) | 1.19 (0.80-1.54) | 0.557 |
Ferritin, mcg/L, median (IQR) | 43.5 (20-176) | 33 (6-75) | 0.556 |
Albumin, mg/dL, median (IQR) | 4.4 (3.9-4.6) | 4.6 (4.2-4.7) | 0.426 |
Creatinine, mg/dL, median (IQR) | 0.75 (0.63-0.96) | 0.91 (0.70-1.09) | 0.349 |
MT-ATP6, ng/L, median (IQR) | 139.9 (130.0-239.2) | 169 (150.5-175.3) | 0.223 |
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (