Distinguishing late onset Combined Immunodeficiency from Common Variable Immunodeficiency

Published Online: August 10, 2016

Common Variable Immunodeficiency (CVID) is the most frequent primary immune deficiency in adults and is characterized by hypogammaglobulinemia and antibody production defect. Major symptoms are recurrent infections, mainly of the upper respiratory tract (Infection only group, OI), requiring immunoglobulin replacement therapy and impacting quality of life. In addition, some patients develop autoimmune or lymphoproliferative complications (Disease-related complication group, DRC) associated with increased morbidity and mortality. The major biological markers for the diagnosis of CVID associate hypogammaglobulinemia are poor vaccine response and reduced number of switch memory B-cells. However, some patients also exhibit clinical or biological evidence of T-cell defect. An updated definition of CVID has been recently proposed by the European Society of Immune Deficiency (ESID) to improve diagnosis.

In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Bertinchamp and colleagues for the DEFI study group (French national cohort of adults with primary hypogammaglobulinemia) have evaluated a new definition for CVID focusing on the exclusion of patients with a severe T-cell defect.

Using the 1999 definition, 351 patients were considered with a diagnosis of CVID. The revised 2014 ESID definition led to the exclusion of only 6 patients (2%) with a severe T-cell defect, without any impact on the survival profile of the CVID group. Based on different T-cell defect surrogate markers (opportunistic infection or a naïve CD4+ T-cell count below 20 x106/L), Bertinchamp and al. have defined a larger group of patients (n=62, 20%) with poor outcome (77% of the deaths). These patients presented with a high prevalence of autoimmune or lymphoproliferative complications and 81% of them initially belonged to the DRC group. After exclusion of these patients, considered as Late Onset Combined Immunedeficiency (LOCID), the CVID group was much more homogeneous with a similar 5-year overall survival in the IO and DRC groups (98.9% and 96.9%, respectively), whereas the overall survival in the LOCID group was only 67.9% at 5-year.

Bertinchamp and al. suggest that the definition of CVID can be improved by detecting and excluding patients with LOCID. These patients deserve specific clinical care and genetic analyses.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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