PMC9889826_01
(A) Thymus volume is significantly reduced. (B) Whole-exome sequencing identifies a 2.520 Mb deletion on chromosome 22q11.21. (C,D) MLPA analysis reveals chromosome 22q11.21 deletion. (E) TCR Vbeta repertoires analyzed by flow cytometry show a diverse and normal distribution of Vbeta subfamilies. (F) Upon stimulation by anti-CD3/anti-CD28 for 4 days, CFSE-labeled CD4 and CD8 T cells from patient PBMCs show a retained proliferative response compared to a healthy control. (G) Changes in patient's lymphocyte, neutrophil, platelet, and hemoglobin (HGB) levels during sirolimus therapy. CFSE, carboxyfluorescein succinimidyl ester; MLPA, multiplex ligation-dependent probe amplification; PBMC, peripheral blood mononuclear cells; TCR, T-cell receptor.
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F1
Computed tomography examination indicated a decreased thymus volume (Figure 1A). Whole-exome sequencing (WES) revealed the presence of a de novo heterozygous 2.520 Mb deletion on 22q11.21 chromosome (18893867-21414817) (Figure 1B). The results revealed a 50% decrease relative to the reference bar height, indicating a heterozygous deletion (Figures 1C,D). Determination of T-cell receptor (TCR) repertoires by flow cytometry revealed that the TCR repertoires of the patient were diverse and normally distributed in CD4 and CD8 T cells (Figure 1E). CD4 and CD8 T cells exhibited a retained potentiality of T cell division (Figure 1F). The patient was followed up for 1 year after sirolimus treatment, and the platelet count was recovered without any other hematologic abnormality being found. Consistent with the clinical improvements, his DNT cells decreased (from 4.4% to 3.2%) along with an elevation of regulatory T cells (Tregs, from 3.7% to 5.2%). ALPS-like manifestations, sirolimus therapy was initiated (1.5 mg/m2, actual blood concentration range: 4.0-5.2 ng/ml) without the addition of other immunosuppressive agents. After 1 month of sirolimus treatment, the whole blood cell counts were gradually restored (Figure 1G), with a decrease in the severity and frequency of infections and bleeding episodes.