High-Titer Antinuclear Antibody Defines a Distinct IgG4-Related Disease Subset With Predilection for Lung and Kidney Involvement

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.

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.

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.

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.