Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles.
BACKGROUND: Common variable immunodeficiency (CVID) is one of the most common primary immune deficiencies. The immunologic hallmark of CVID is failure of B-cell differentiation and impaired secretion of immunoglobulins. However, there is mounting evidence of accompanying T-cell dysregulation, which could be due to abnormal thymic function because the thymus plays a crucial role in T-cell development. Recently, it was shown that the human thymus remains functional well into adulthood. Current data show that the level of T-cell receptor excision circles (TRECs) correlates well with active thymopoiesis. OBJECTIVE: To determine whether thymic dysfunction contributes to the pathogenesis of CVID. METHODS: We evaluated 15 patients, aged 19 to 65 years, previously diagnosed as having CVID. Genomic DNA was isolated from peripheral blood mononuclear cells of each patient. Thymic output was evaluated by measuring coding joint TRECs in the total T-cell population using real-time polymerase chain reaction. RESULTS: Results were compared with known age-matched reference values. The median TREC level in patients with CVID (82,034 copies/microg of DNA) was significantly higher than that in the healthy cohort (43,000 copies/microg of DNA) (P < .001). In examining the relationship between TREC levels and age, we noted that TREC levels significantly declined faster with age in patients with CVID vs the healthy cohort. CONCLUSIONS: In these patients, thymic dysregulation may be a factor in CVID, with an accelerated rate of TREC loss with age compared with healthy adults.