The clinical relevance of IgM and IgA anti‐pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency

Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)‐antibodies, PnPS IgA and IgM‐antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA‐PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti‐PnPS IgM and IgA‐assays in patients with suspected primary immunodeficiency in a large teaching hospital in ’s‐Hertogenbosch, the Netherlands. Serotype‐specific‐PnPS IgG assays were performed; subsequently, 23‐valent‐PnPS IgG assays (anti‐PnPS IgG assays), and later anti‐PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre‐ and six of 10 post‐immunization samples from good responders to PnPS serotype‐specific IgG testing had decreased anti‐PnPS IgA and/or IgM titres. Of these, three pre‐ and no post‐immunization samples were from patients previously classified as ‘no PAD’. Determination of anti‐PnPS IgA and IgM in addition to anti‐PnPS IgG did not reduce the need for serotype‐specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post‐immunization samples: anti‐PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63–0.97; anti‐PnPS IgM + IgG AUC 0.80, 95% CI = 0.62–0.98; anti‐PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51–0.91; anti‐PnPS IgG AUC = 0.93, 95% CI = 0.85–1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype‐specific PnPS IgG can still display impaired anti‐PnPS IgM and IgA responses, and that the additional measurement of anti‐PnPS IgA and IgM could not reduce the need for serotype‐specific IgG testing. Future studies are needed to investigate the clinical relevance of potential ‘specific IgA or IgM antibody deficiency’ in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.