Serum IgM and Soluble IL-2 Receptor as Predictors of Granulomatous-Lymphocytic Interstitial Lung Disease in CVID

Introduction with Aim Granulomatous-lymphocytic interstitial lung disease (GLILD) develops in 10–30% of patients with common variable immunodeficiency (CVID) as a consequence of immune dysregulation. Therefore, immunoglobulin (Ig) M, produced by apoptosis-resistant plasmablasts in extrafollicular sites in the lungs, and serum soluble interleukin-2 receptor (sIL-2R), shed by activated T lymphocytes, can both be elevated. The aim of this study was to evaluate whether these biomarkers are associated with higher risk of GLILD development. Materials and Methods A retrospective single-center case-control study was conducted comparing CVID patients with GLILD (n = 9) and without GLILD (n = 13). Concentrations of IgM (normal/elevated normal vs. low/undetectable) were compared between the groups using Fisher’s exact test. Due to technical limitations, the concentration of sIL-2R was measured only in several patients. Results No statistically significant association was found between GLILD and IgM concentration (normal/elevated normal vs. low/undetectable) (p = 0.66), although patients with normal/elevated normal IgM levels had twofold higher odds of having GLILD (odds ratio [OR] 2; 95% confidence interval [CI] 0.36–11.2). The wide CI suggests the main limitation of our study: the small sample size (22 CVID patients in total). Preliminary data also showed that sIL-2R concentrations were significantly elevated in patients with GLILD (mean 1,059 IU/mL, normal <350 IU/mL). Conclusion Even though statistical significance was not shown, the results illustrate that elevated IgM levels may be associated with an increased risk of GLILD, suggesting a potential role for IgM in disease pathogenesis. Furthermore, higher sIL-2R levels reinforce the concept of immune dysregulation as a key feature of this CVID phenotype. Larger, multicenter studies with greater sample sizes are needed to clarify this potential association. If confirmed, longitudinal monitoring of these biomarkers could contribute to the earlier identification of CVID patients at higher risk of developing GLILD.