Correlation between common variable immunodeficiency clinical phenotypes and parental consanguinity in children and adults.

BACKGROUND

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders with a wide range of clinical manifestations and immunological findings, which could possibly form the basis for classification into different phenotypes.

OBJECTIVES

This study was performed to distinguish between different clinical phenotypes in Iranian patients with CVID and compare complications and prognosis between these subgroups.

METHODS

Ninety-three CVID patients were classified according to 5 clinical phenotypes: infections only (n=42), polyclonal lymphocytic infiltration (n=35), autoimmunity (n=10), malignancy (n=10), and enteropathy (n=9). The patients were further categorized into 4 groups based on age of diagnosis (cutoff, 13 years) and parental consanguinity.

RESULTS

Grouping of patients showed that CVID children with parental consanguinity was the most frequent group (51%), followed by CVID children without parental consanguinity (21%), CVID adults without parental consanguinity (21%), and CVID adults with parental consanguinity (7%). There were significant associations between the group of CVID children with parental consanguinity and the polyclonal lymphocytic infiltration (P=.011) and enteropathy (P=.048) phenotypes. This group also had a higher mortality rate than other groups (P=.014). High serum levels of immunoglobulin M (IgM) at the time of diagnosis were associated with the eventual development of autoimmunity (P=.023). The adjusted odds ratio (OR) for mortality in all phenotypes showed that mortality was significantly increased in patients with the polyclonal lymphocytic infiltration phenotype (Mantel-Haenszel OR=5.3, CI=3.42-6.2).

CONCLUSIONS

Parameters such as parental consanguinity and early onset of disease could describe a subgroup of CVID patients characterized by more complications, poorer prognosis, and a need for greater medical care and attention.