Mortality in Antinuclear Antibody-Positive Patients with and Without Rheumatologic Immune-Related Disorders: A Large-Scale Population-Based Study.
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All Authors
Shani, U.
David, P.
Balassiano Strosberg, I.
Regev, O.
Yihia, M.
Ben-Shabat, N.
McGonagle, D.
Weinstein, O.
Amital, H.
Watad, A.
LTHT Author
David, Paula
McGonagle, Dennis
Watad, Abdulla
McGonagle, Dennis
Watad, Abdulla
LTHT Department
NIHR Leeds Biomedical Research Centre
Rheumatology
Musculoskeletal
Rheumatology
Musculoskeletal
Non Medic
Publication Date
2025
Item Type
Journal Article
Language
Subject
Subject Headings
Abstract
Background & Objectives : To explore the potential association between positive ANA serology and all-cause mortality in a large cohort of patients, including those with and without rheumatological conditions and other immune-related diseases. Material and Methods: A retrospective cohort study analyzed all-cause mortality among 205,862 patients from Clalit Health Services (CHS), Israel's largest health maintenance organization (HMO). We compared patients aged 18 and older with positive ANA serology (n = 102,931) to an equal number of ANA-negative controls (n = 102,931). Multivariable Cox regression models were used to assess hazard ratios (HR) for mortality, adjusting for demographic and clinical factors. Results: ANA positivity was strongly associated with increased mortality (adjusted HR [aHR] 4.62; 95% CI 4.5-4.7, p < 0.001). Significant predictors of mortality included male gender (39.2% vs. 24.4%, p < 0.001), older age at testing (72.4 +/- 13.0 vs. 50.1 +/- 17.3 years, p < 0.001), and Jewish ethnicity (89.6% vs. 83.2%, p < 0.001). Certain ANA patterns, such as mitochondrial (and dense fine speckled (DFS-AC2)), were highly predictive of mortality, with aHRs of 36.14 (95% CI 29.78-43.85) and 29.77 (95% CI 26.58-33.34), respectively. ANA-positive patients with comorbid rheumatological immune-related disorders (RIRDs) demonstrated a higher survival rate compared to those without such a condition (aHR 0.9, 95% CI 0.86-0.95, p < 0.001). This finding remained significant after adjusting for several parameters, including age. Conclusions: ANA positivity is associated with increased all-cause mortality, particularly in individuals without rheumatologic disorders, after adjusting for confounders such as age. This may indicate occult malignancies, cardiovascular pathology, or chronic inflammatory states, necessitating more vigilant surveillance.
Journal
Medicina (Kaunas, Lithuania)