Invasive pneumococcal disease unmasks monoclonal immunoglobulins and antibody deficiencies: a multicenter prospective study in adults

Immunoglobulins (Ig) are essential for protection against invading pneumococci but are not routinely analyzed in patients with invasive pneumococcal disease (IPD). In this prospective study, we assessed the prevalence of monoclonal Ig (M protein) and analyzed Ig concentrations in sera from 156 adult IPD patients (median age 70 years). Patients were sampled during acute infection (n = 153) and in the convalescence phase 2-4 months after acute infection (n = 76). Sixty-four sex- and age-matched individuals without IPD served as controls. During infection, M protein was detected in 22% (31/141) of patients without previously known hematological malignancy as compared with 5% of the controls (p = 0.002). Seven of these patients were subsequently diagnosed with a hematological malignancy, including multiple myeloma, Waldenstrom macroglobulinemia, and mantle cell lymphoma. Another 12 patients were diagnosed with monoclonal gammopathy of undetermined significance (MGUS). Convalescence levels of IgA, IgG2, or IgG4 were below the reference intervals in 16-20% of patients and 0-2% of controls. Three patients were diagnosed with a primary Ig deficiency, and seven patients started Ig replacement therapy. Our findings suggest that assessment of M protein and Ig levels could be considered in adults with IPD, as an episode of IPD may unmask a previously undiagnosed B-cell malignancy or immunodeficiency.