Comparison of Diagnostic Criteria for Common Variable Immunodeficiency Disorder

Abstract

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.

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

“…5 About 15 years later, two different revisions of the ESID/PAGID 1999 criteria were made: the Ameratunga 2013 criteria 6 and the revised ESID registry 2014 criteria. 7 Remarkably, both revisions proposed reduced (switched) memory B cells as an alternative criterion for impaired vaccine responses. 7 The revised ESID registry 2014 criteria additionally stated that both IgG and IgA must be decreased to confer a diagnosis of CVID.…”

“…7 Remarkably, both revisions proposed reduced (switched) memory B cells as an alternative criterion for impaired vaccine responses. 7 The revised ESID registry 2014 criteria additionally stated that both IgG and IgA must be decreased to confer a diagnosis of CVID. 7 However, not all practitioners agree on the obligatory decrease in IgA.…”

T-Cell Abnormalities in Common Variable Immunodeficiency

“…+ T cells at 2-6 years <25%, 6-16 years <20%, >16 years <10%; and (3) absence of T-cell proliferation [18]. CVID patients who experience profound T-cell deficiency are considered to have combined immunodeficiency (CID) [19,20].…”

Flow Cytometry, a Versatile Tool for Diagnosis and Monitoring of Primary Immunodeficiencies

“…This is an example of an elderly female patient with a history of being a carrier for XL-CGD and who has an affected male offspring demonstrating age-related extreme skewing of lyonization with a DHR flow pattern similar to that seen in a male patient with XL-CGD. cluding susceptibility to sinopulmonary infections, granulomatous disease, lymphoproliferation, and autoimmunity (in subsets of patients) (88)(89)(90). Attempts have been made over the past decade or longer to classify CVID patients based on differences in peripheral B cell subsets, and some of these have provided clinical correlations, which may have prognostic value in subgroups of patients (91)(92)(93)(94)(95)(96)(97)(98).…”

“…Attempts have been made over the past decade or longer to classify CVID patients based on differences in peripheral B cell subsets, and some of these have provided clinical correlations, which may have prognostic value in subgroups of patients (91)(92)(93)(94)(95)(96)(97)(98). B cell subset analysis, in particular evaluation of memory B cells and switched memory B cells, has been incorporated into the newer diagnostic criteria as an accessory criterion (88), as the majority of CVID patients have impaired peripheral B cell differentiation and reduced class-switched memory B cells. Most clinical laboratories that offer B cell subset immunophenotyping include assessment of various memory B cell subsets, including marginal zone B cells (…”