Associations between disease factors and clinical outcomes in common variable immunodeficiency: a systematic literature review.

Common variable immunodeficiency (CVID) is associated with diverse clinical manifestations. This systematic review aimed to explore associations between disease factors and clinical outcomes in patients with CVID. Eligible studies included patients with CVID and reported associations between disease factors and clinical outcomes (e.g., autoimmune cytopenia, bronchiectasis, infections, lung damage, malignancy, and mortality). Quality assessment was conducted using the Newcastle-Ottawa Scale. Thirty-nine studies met inclusion criteria. The occurrence of lymphadenopathy or splenomegaly was associated with an increased risk of autoimmune cytopenia and lung damage specific to granulomatous-lymphocytic interstitial lung disease; splenomegaly was associated with increased risk of bronchiectasis. Higher levels of switched memory B (smB) cells and marginal zone B cells were associated with reduced risks of lung damage; higher levels of smB cells were associated with a reduced risk of autoimmune cytopenia. Elevated CD21low B cells were associated with increased risks of autoimmune cytopenia, lung damage, and infections. Higher total B cells were associated with lower risk of bronchiectasis and mortality. These findings suggest specific relationships are present between lymphoproliferation markers and B-cell subsets and clinical outcomes in CVID. Limitations including heterogeneity in study designs and low- to moderate-quality evidence underscore the need for additional research to validate these associations.