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

Unlike IgG 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). 11/65 pre-immunisation and 6/10 post-immunisation samples from good responders to PnPS-serotype-specific IgG-testing, had decreased anti-PnPS IgA and/or IgM-titres. Of these, three pre-immunisation and no post-immunisation 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 (ROC-analysis of post-immunisation samples: anti-PnPS IgA+IgG AUC 0.80(95%-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, still can 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.