The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency

Background: Recurrent lower respiratory tract infections caused by encapsulated bacteria might cause permanent organ damage in patients with common variable immunodeficiency (CVID). Despite the profound hypogammaglobulinemia, some patients do not experience bacterial pneumonia. We have shown that IgM memory B cells and natural antibodies play an important role in the defense against encapsulated bacteria. Objective: In this study we addressed the question of whether the apparent paradox of patients with severe hypogammaglobulinemia but no increased frequency of respiratory infections can be explained by the presence of IgM memory B cells and anti-pneumococcal polysaccharide (anti-PnPS) IgM. Methods: We measured the frequency of memory B cells and the levels of anti-PnPS IgM antibodies in 26 patients with CVID with recurrent bacterial pneumonia and bronchiectasis (group 1) and 22 who never had pneumonia and showed no lung lesions (group 2). An additional 6 patients had a clinical history of recurrent pneumonia without lung abnormalities at computed tomographic scanning. Results: Patients of group 1 lacked IgM memory B cells and failed to produce anti-PnPS IgM antibodies, and those of group 2 had a normal frequency of IgM memory B cells and produced anti-PnPS IgM antibodies. Conclusions: IgM memory B cells and anti-PnPS IgM antibodies protect patients with CVID from bacterial pneumonia. Evaluation of these 2 parameters discriminates patients with low or high risk of recurrent infections caused by encapsulated bacteria and low or high risk of bronchiectasis. Identification of high-risk individuals at diagnosis might help in the planning of a more effective therapeutic strategy and prevent permanent organ damage.