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ABS0933 (2025)
EVALUATION OF MITOCHONDRIAL DYSFUNCTION USING MT-ATP6 LEVELS IN ANCA-ASSOCIATED VASCULITIS AND IgG4-RELATED DISEASE
Keywords: Biomarkers, Prognostic factors, Diagnostic test
R. C. Kardaş1, İ. Vasi1, D. Yildirim1, B. Kaya1, R. Duran1, İ. Y. Çakir1, İ. Karaduman1, H. Küçük1, B. Göker1, M. A. Öztürk1, A. Erden1
1Gazi University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye

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 ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.


DOI: annrheumdis-2025-eular.B3553
Keywords: Biomarkers, Prognostic factors, Diagnostic test
Citation: , volume 84, supplement 1, year 2025, page 1532
Session: Across diseases (Publication Only)