Common Variable Immune Deficiency in Children—Clinical Characteristics Varies Depending on Defect in Peripheral B Cell Maturation

Abstract

Common variable immune deficiency (CVID) is a heterogeneous disease associated with ineffective production of antibodies. It is usually diagnosed in adulthood, but a variable proportion of children develop CVID. Early identification of patients with potentially worse prognosis may help to avoid serious complications. The goal of this study was to associate the clinical phenotype of patients with early onset CVID with peripheral B-cell maturation profile. Four color flow cytometry was used to define distribution of peripheral B-cell subsets in 49 children with early-onset CVID. All clinical data were extracted from medical records. A proportion of patients demonstrated diminishing with time total B-lymphocytes pool, beyond physiological age-related changes. Irrespective from duration of the follow-up period the B-cell maturation profile in individual patients remained unchanged. We identified six different aberrant peripheral B cell maturation profiles associated with different clinical characteristics. Patients with an early B-cell maturation block earlier required replacement therapy and were at significantly greater risk of enteropathy, granuloma formation, cytopenia, and lymphoproliferation. B-cell maturation inhibited at the natural effector stage was associated with higher risk of autoimmune manifestations other than autoimmune cytopenia. Prevalence of male patients was observed among patients with B-cell maturation inhibited at naïve B-cell stage. In conclusion, the diagnostic process in patients with suspected early-onset CVID shall include routine analysis of peripheral B-cell maturation to provide surrogate markers identifying patients at greater risk of developing certain complications.

International Consensus Document (ICON): Common Variable Immunodeficiency Disorders

“…243,244 Furthermore, recurrent infections, chronic inflammation, chronic nutritional deficits, and associated gastrointestinal abnormalities may pose threats to optimal growth in children. Bronchial hyperreactivity associated with allergen sensitization may be seen in some children with CVID.…”

B‐cell subpopulations in children: National reference values

“…Since 2008, several studies have highlighted the importance of age‐specific reference intervals for the correct interpretation of B‐cell subpopulation data from children for diagnostic purposes . However, only adult classifications currently exist, and these must be adapted to the maturation state of the immune systems of children of various ages . We established national reference values for B‐lymphocyte subpopulations in the peripheral blood of healthy children.…”

“…A European classification has been put forward in which subgroups of CVID patients are defined on the basis of the percentages of transitional and memory B-cells in adults [24]. Since 2008, several studies have highlighted the importance of age-specific reference intervals for the correct interpretation of B-cell subpopulation data from children for diagnostic purposes [25][26][27][28][29]. However, only adult classifications currently exist, and these must be adapted to the maturation state of the immune systems of children of various ages [25][26][27][28][29].…”

Antibody Deficiency

“…23,24 The T cell phenotype is also variable. As with CVID and IGAD, caution should be exercised when conferring this diagnosis in patients less than 4 years of age.…”