Levels of immunoglobulin isotypes in serum and respiratory samples of patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

COPD is a disease of progressive and irreversible airflow obstruction, with exacerbations (AECOPD) often triggered by infection. Immunoglobulins play an important role in immune defense and immune regulation, however their role in COPD is poorly understood. Therefore, the purpose of our systematic review and meta-analysis was to assess serum, sputum, and bronchoalveolar lavage (BAL) levels of IgG, IgG subclasses, IgA, and IgM in COPD, and the association between immunoglobulins and key clinical outcomes. EMBASE and Ovid MEDLINE were searched from inception to April 2024. Study screening and extraction were completed by two independent reviewers. Non-randomized studies assessing immunoglobulin levels were included. Data was analyzed using RevMan 5. Our search identified 1897 studies; 36 were included in meta-analysis. Compared with healthy controls, individuals with COPD showed elevated secretory IgA levels (Standard Mean Difference (SMD) 1.68 [95% Confidence Interval (CI), 0.78, 2.59], N = 2). IgG2 was significantly lower in COPD compared to controls [SMD − 0.91 (-1.24, -0.58)]. There was no significant SMD in other IgG subclasses, serum IgG, IgM, or BAL IgA. Serum IgG and subclass levels did not differ between stable and AECOPD (SMD 0.10 [-0.61, 0.81]). Compared to COPD with normal IgG, the COPD-low IgG group had increased risk of COPD admissions (OR 1.32 [95% CI, 1.11, 1.56]), lower FEV1/FVC % (SMD − 2.26[-3.3, -1.14] and FVC (SMD − 0.31[-0.58, -0.05]). Systemic steroid use trended higher in COPD-low IgG (OR 2.32[0.94, 5.72]). There was no difference in 1-year mortality. In conclusion, serum IgG2 was lower in COPD and low IgG was associated with increased COPD-related admissions. These findings support further investigation of IgG as a potential biomarker and therapeutic target in COPD.