Integrating TREC/KREC assay and some cytokines in the evaluation of the immune status of patients with DiGeorge Syndrome

Abstract

Aim The study aimed to offer better genetic evaluation and consultation for DiGeorge syndrome (DGS) patients by combining screening of 22q11.2 and immunologic studies. A basic immune profile including the basic CD panel and immunoglobulins estimation was performed. TRECS and KRECS expression were studied in addition to measuring serum IL33, Obestatin, HLA-G, and Procalcitonin serum levels. Methods All investigations were performed for DGS patients (n = 33) and the matched control group (n = 45). Polymorphic 22q11.2 markers mapping was performed by PCR-STR technique. Lymphocyte subsets immunophenotyping was done using flow cytometry, while measurement of serum immunoglobulins was estimated using nephelometry. Real-time PCR was the method used for TRECs and KRECs measurement. Serum IL33, Obestatin, HLA-G, and Procalcitonin levels were determined using an Enzyme-linked immunosorbent assay (ELISA). Data was coded, tabulated, and statistically analyzed using SPSS version 19.0 software. Results In our case–control study, KREC expression was significantly elevated in DGS compared to healthy controls (P = 0.0008). There was also a significant increase in immunoglobulin levels in DGS. CD8% as well as CD8 absolute count in the patients with DGS were significantly lower than in the healthy control (P = 0.01273 and 0.05358 respectively). There were no significant differences in IL33, Obestatin, HLA-G, and Procalcitonin levels between DGS patients compared to the control group. Our results concerning the distinct segment of 22q11.2 as a DGS susceptibility region revealed an informative novel atypical interstitial homozygous deletion. This deletion included D22S944 and COMT absence, and D22S941 and D22S264 presence. Out of 33 DGS patients, three patients showed deletion in the D22S944 marker only in the presence of D22S941, and D22S264 markers. Therefore, we could assume that D22S944 is a common deleted marker in non-isolated DGS patients. Conclusion Combining 22q11.2 region screening, immune profile studies, and TRECS and KRECS expression offers a new comprehensive approach for DGS patients. This approach provides a better strategy for genetic consultation for DGS patients. Moreover, this study may be the first to show a small interstitial 22q11.2 deletion stereotype in a DGS patient and also showed that the smallest deletion at the 22q11.2 region is enough to confer the DGS phenotype.