Truly selective primary IgM deficiency is probably very rare

SUMMARY

Isolated decreased serum-IgM has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary center population studied so far. Also, many papers on IgM-deficiency have included patients with more abnormalities than just IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies ESID (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and retrospectively analyzing all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands (1-July-2005 to 23-March-2016; n=8,049 IgM<0.4g/l; n=2,064 solitary [IgG+IgA normal/IgM<age-matched reference]). 359/2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45/359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only 6/261 (2%) literature cases and 3/45 (7%) cases from our cohort completely fulfilled the ESID criteria; 63/261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG-subclasses and/or vaccination responses were lacking in 192/261 (74%) literature cases and 42/45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to fully explore its clinical consequences. The ESID online Registry would be a good tool for this. This article is protected by copyright. All rights reserved.