TRECs levels in children with PIDs and secondary immunodeficiency
To confirm the specificity and sensitivity of our method, we analyzed TRECs levels in patients with SCID and X linked agammaglobulinemia (XLA). TRECs levels in patients with SCID of the IL2rg, RAG1, JAK3, and Lig4 mutation genotypes were 0, whereas those in patients with XLA were normal (Table 1), which is consistent with previous publications21.
Next, we determined the significance of TRECs levels in PIDs (Table 2). We identified greater reductions in TRECs levels in patients with classical WAS, whereas those in X linked thrombocytopenia (XLT) patients were only slightly decreased or within the normal ranges (Fig. 6). These data suggest that TRECs levels could be used to identify classical WAS or XLT early, thereby enabling appropriate selection of therapeutics. However, the data may mean that classical WAS might be caused by a thymic output defect22. Gain-of-function (GOF) mutations in PIK3CD cause APDS. Therefore, we asked whether there was a clear reduction in TRECs levels in APDS, consistent with other combined immunodeficiency (CIDs). We found that TRECs levels in most patients with STAT1 mutations were normal, although some did have lower levels (Fig. 6). We also analyzed the lymphocyte subsets from STAT1 patients (Table 3) and found that changes in TRECs levels were consistent with changes in CD4 naïve T cell numbers in STAT1 patients (Fig. 7).
In addition, we analyzed TRECs levels in patients with secondary immunodeficiencies such as primary nephrotic syndrome (NS) after prednisone treatment. We found that TRECs levels were normal in NS patients with or without immunosuppressive treatment (Table 4 and Fig. 8).