Truly selective primary IgM deficiency is probably very rare

Area of Science:

• Immunology
• Clinical Medicine

Background:

• Isolated decreased serum-immunoglobulin (IgM) is linked to infections, atopy, and autoimmunity.
• Previous studies may overestimate clinical problems due to studying tertiary center populations and including patients with broader immune abnormalities.

Purpose of the Study:

• To investigate the prevalence and diagnostic certainty of truly selective primary IgM deficiency (true sIgMdef) based on European Society for Immunodeficiencies (ESID) criteria.
• To assess the clinical relevance of isolated decreased serum IgM.

Main Methods:

• Literature review of 261 patients with primary decreased serum-IgM.
• Retrospective analysis of 8049 patients with decreased serum-IgM in a Dutch teaching hospital, focusing on 2064 with solitary IgM deficiency.
• Review of medical charts for 45 persistent cases from the hospital cohort.

Main Results:

• True sIgMdef is rare, meeting ESID criteria in only 2% of literature cases and 7% of hospital cases.
• A significant proportion of literature cases (24%) had other immunological abnormalities, meeting criteria for unclassified antibody deficiencies (unPAD).
• Diagnosis was often uncertain due to missing data on IgG subclasses and/or vaccination responses (74% of literature cases, 93% of hospital cases).

Conclusions:

• The study suggests that true selective primary IgM deficiency is likely very rare.
• Determining the clinical relevance of decreased serum IgM presents a diagnostic challenge.
• A larger cohort of true sIgMdef patients is required, and the ESID online Registry could aid this research.