Utility of simultaneous quantification of TREC/KREC in patients with common variable immunodeficiency phenotype: an observational study from North India.

Abstract

Because of its heterogeneity, common variable immunodeficiency (CVID), the commonest symptomatic inborn error of immunity, is difficult to classify. Limited data suggest T-cell receptor excision circles (TREC) and kappa-deleting re-combination excision circles (KREC) may be useful to better classify and prognosticate CVID and CVID phenotype. Thirty-four patients with CVID/CVID phenotype and 30 healthy controls were included in this cross-sectional observational study. Simultaneous quantification of TREC/KREC was performed using multiplex real-time polymerase-chain reaction with TaqMan probes. The levels of TREC/KRECs were analyzed for any association with clinical features, immunological investigations, and molecular studies. Median values of KREC and TREC copy numbers in patients with CVID/CVID phenotype were 64.5 and 170 copies/50 ng reaction, respectively, whereas the median values in controls were 79.2 and 190.1 copies/50 ng reaction respectively. We classified the patients into 4 groups based on copy numbers of TREC/KRECs: (A)TREC + /KREC + ; (B) TREC + /KREC-; (C) TREC-/KREC + ; (D)TREC-/KREC- [" + " and " - " denotes TREC/KREC levels above and below median value respectively]. Patients in Group B had higher risk of developing bronchiectasis. There was no significant difference vis-à-vis failure to thrive, infections, autoimmunity and malignancy, and levels of immunoglobulins, CD19⁺ B cells, and CD4:CD8 ratio amongst the 4 groups. Monogenic defects (n = 10/34) were more likely when age of onset was $\le$ 4 years (p = 0.02), irrespective of TREC/KREC copy numbers. Classification of CVID/CVID phenotype based on TREC/KREC levels may not be feasible; however, a sub-group with low KREC/normal TREC levels may be predisposed to develop bronchiectasis. Patients with younger age of onset (< 4 years) were more likely to have monogenic defects.