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Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision
Michelle J De Vera1, Lena Al-Harthi, Anita T Gewurz
1Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois 60612, USA.
Insights
Thymic dysfunction may contribute to Common Variable Immunodeficiency (CVID). Patients with CVID showed higher T-cell receptor excision circles (TRECs) and a faster decline with age, indicating thymic dysregulation.
Area of Science:
- Immunology
- Human Physiology
Background:
- Common Variable Immunodeficiency (CVID) is a primary immune deficiency characterized by B-cell defects and low immunoglobulins.
- Evidence suggests T-cell dysregulation in CVID may stem from impaired thymic function.
- The thymus remains active in adults, and T-cell receptor excision circles (TRECs) indicate thymic output.
Purpose of the Study:
- To investigate if thymic dysfunction plays a role in the development of CVID.
- To assess thymic output in adult CVID patients.
Main Methods:
- Evaluated 15 adult CVID patients (aged 19-65).
- Measured T-cell receptor excision circles (TRECs) in peripheral blood mononuclear cells via real-time PCR to assess thymic output.
- Compared TREC levels to age-matched healthy individuals.
Main Results:
- Patients with CVID had significantly higher median TREC levels (82,034 copies/μg DNA) compared to healthy controls (43,000 copies/μg DNA).
- TREC levels declined more rapidly with age in CVID patients than in the healthy cohort.
- This suggests an accelerated loss of thymic function in CVID.
Conclusions:
- Thymic dysregulation appears to be a contributing factor in the pathogenesis of CVID.
- Accelerated loss of thymic function, indicated by faster TREC decline, is observed in CVID patients compared to healthy adults.
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.
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