SummaryCommon variable immune deficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults. The standard of care is intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (scIG) therapy. The cause of CVID is currently unknown, and there is no universally accepted definition of CVID. This creates problems in determining which patients will benefit from IVIG/scIG treatment. In this paper, we review the difficulties with the commonly used European Society of Immune Deficiencies (ESID) and the Pan American Group for Immune Deficiency (PAGID) definition of CVID. We propose new criteria for the diagnosis of CVID, which are based on recent scientific discoveries. Improved diagnostic precision will assist with treatment decisions including IVIG/ scIG replacement. We suggest that asymptomatic patients with mild hypogammaglobulinaemia are termed hypogammaglobulinaemia of uncertain significance (HGUS). These patients require long-term follow-up, as some will evolve into CVID.

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information. Here, we compare the revised European society of immune deficiencies (ESID) registry (2014) criteria with the diagnostic criteria of Ameratunga et al. (2013) and the original ESID/pan American group for immune deficiency (ESID/PAGID 1999) criteria. The ESID/PAGID (1999) criteria either require absent isohemagglutinins or impaired vaccine responses to establish the diagnosis in patients with primary hypogammaglobulinemia. Although commonly encountered, infective and autoimmune sequelae of CVID were not part of the original ESID/PAGID (1999) criteria. Also excluded were a series of characteristic laboratory and histological abnormalities, which are useful when making the diagnosis. The diagnostic criteria of Ameratunga et al. (2013) for CVID are based on these markers. The revised ESID registry (2014) criteria for CVID require the presence of symptoms as well as laboratory abnormalities to establish the diagnosis. Once validated, criteria for CVID will improve diagnostic precision and will result in more equitable and judicious use of intravenous or subcutaneous immunoglobulin therapy.

RESPONSE TO: Kumar R, Bhatia A. Common variable immunodeficiency in adults: current diagnostic protocol and laboratory measures. Expert Rev. Clin. Immunol. 10(2), 000-000 (2014).

The C104R mutation does not correlate with the clinical phenotypes in this family.