Abstract Rationale Primary antibody deficiencies are the most common innate errors of immunity, particularly common variable immunodeficiency. Many patients develop pulmonary complications, especially infections and bronchiectasis, but some present with interstitial lung disease (ILD), termed GLILD. Because of its rarity, clinical, radiologic, pathologic, and functional characterization remains limited. We aimed to describe the features of GLILD patients from a single tertiary center and explore factors associated with lung function impairment. Methods We conducted a cross-sectional analysis of 25 adults with GLILD followed at a tertiary ILD clinic. Diagnosis was established by multidisciplinary consensus. Variables included demographics, extrapulmonary manifestations, immunoglobulin levels, CT classification (Galant-Swafford et al., 2024), and pulmonary function. Group comparisons used t-tests/ANOVA, and linear and logistic regressions were performed for FVC (L), DLCO %pred, and FVC ≤ 75 %. Results Mean age was 38.3 ± 16.1 years; 80 % were female. Median time since CVID diagnosis was 6 years (IQR 3-10) and since GLILD diagnosis 2 years (IQR 1-4). Extrapulmonary findings included lymphadenopathy (80 %), splenomegaly (76 %), and cytopenias (44 %). Most received IgG replacement (92 %) and about half were on immunomodulatory therapy (IT). CT patterns were GLILD-compatible (52 %), typical (40 %), and favoring alternative diagnosis (8 %). Mean FVC %pred was 76 ± 24 %, and DLCO %pred (n = 13) 60 ± 26 %. Treated patients had significantly lower FVC (L) (2.33 ± 1.0 vs 3.40 ± 0.9, p = 0.007), FVC % (64 ± 24 vs 89 ± 18 %, p = 0.004), and DLCO % (48.8 ± 16 vs 78.4 ± 30.9 %, p = 0.021). CT classification was not associated with function (p 0.4). In linear regression including CT classification, bronchiectasis, and treatment, IT remained independently associated with lower DLCO % (p = 0.041; R² = 0.42). In logistic regression, time since GLILD diagnosis correlated with FVC ≤ 75 % (OR 1.59, 95 % CI 1.02-2.59, p = 0.039), with a trend for lower FVC in treated patients (OR 8.08, p = 0.056). Conclusion In this single-center cohort, GLILD patients showed typical features—female predominance, lymphadenopathy, and splenomegaly. Those on immunosuppressive therapy had markedly reduced FVC and DLCO, even after adjustment, suggesting more advanced disease. CT classification did not correlate with function. Longer GLILD duration associated with FVC ≤ 75 % indicates possible progressive impairment. These findings highlight the need for longitudinal studies to clarify its natural history and treatment response. This abstract is funded by: None
Amaral et al. (Fri,) studied this question.