High‐Titer Antinuclear Antibody Defines a Distinct IgG4‐Related Disease Subset With Predilection for Lung and Kidney Involvement
Jie Zhang, Yurong Zhao, Yiwen Wang, Chao Xue, Lidong Hu, Jianglin Zhang, Jian ZhuObjective
This study investigated whether antinuclear antibody (ANA) positivity identifies a distinct clinical phenotype in IgG4‐related disease (IgG4‐RD), characterized by specific organ involvement patterns.
Methods
We conducted a cohort study of patients diagnosed with IgG4‐RD (2016–2024). Based on indirect immunofluorescence (IIF) results, patients were categorized as ANA‐negative (titer ≤ 1:100) or ANA‐positive, with the latter further stratified by titer: group 1 (moderate titer, 1:320) and group 2 (high titer, ≥1:1000). We comprehensively compared demographics, organ involvement, and laboratory profiles across groups. Multivariable logistic regression was used to quantify associations.
Results
Among 278 patients, 38 (13.7%) were ANA‐positive ( n = 19 per titer‐based subgroup). ANA patterns differed: granular in group 1 versus homogeneous/granular homogeneous in group 2. Only patients in group 2 (high‐titer ANA) demonstrated a significantly elevated risk of lung and kidney initial onset and involvement compared to ANA‐negative patients. This group also exhibited marked hypocomplementemia. The adjusted odds ratios for lung and kidney involvement in group 2 were 10.18 (95% CI: 3.590–28.876) and 4.42 (95% CI: 1.605–12.151), respectively. No such associations were found in group 1.
Conclusion
IgG4‐RD combined with high‐titer ANA (≥1:1000), mainly presenting as homogeneous type or homogeneous granular type, characterized by a heightened propensity for lung and kidney, initial onset and involvement, and hypocomplementemia. Routine ANA testing and careful assessment of pulmonary and renal systems are warranted in these patients.