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Clinical and Laboratory Factors Affecting the Prognosis of Severe Combined Immunodeficiency

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A Correction to this article was published on 11 March 2023

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Abstract

Purpose

Severe combined immunodeficiency (SCID) is one of the most severe forms of inborn errors of immunity characterized by absence or loss of function in T cells. The long-term outcomes of all forms of SCID have been evaluated in a limited number of studies. We aimed to evaluate the pre- and post-transplant manifestations of SCID patients and determine the factors affecting the survival of patients.

Methods

We included 54 SCID patients (classical SCID, Omenn syndrome, atypical SCID (AS)) in this study. We evaluated the clinical presentation, infections, and outcome of hematopoietic stem cell transplantation (HSCT). Lymphocyte subsets and T-cell receptor (TCR) repertoire were analyzed by flow cytometry.

Results

The median age at diagnosis was 5 (range: 3–24) months and follow-up time was 25 (range: 5–61) months. Symptom onset and diagnostic ages were significantly higher in AS compared to others (p = 0.001; p < 0.001). The most common SCID phenotype was T-B-NK + , and mutations in recombination-activating genes (RAG1/2) were the prominent genetic defect among patients. The overall survival (OS) rate was 83.3% after HSCT, higher than in non-transplanted patients (p = 0.001). Peripheral blood stem cell sources and genotypes other than RAG had a significant favorable impact on CD4+ T cells immune reconstitution after transplantation (p = 0.044, p = 0.035; respectively). Gender matching transplantations from human leukocyte antigen (HLA)–identical and non-identical donors and using peripheral blood stem cell source yielded higher B-cell reconstitution (p = 0.002, p = 0.028; respectively). Furthermore, receiving a conditioning regimen provided better B-cell reconstitution and chimerism (p = 0.003, p = 0.001). Post-transplant TCR diversity was sufficient in the patients and showed an equal distribution pattern as healthy controls. The OS rate was lower in patients who underwent transplant with active infection or received stem cells from mismatched donors (p = 0.030, p = 0.015; respectively).

Conclusion

This study identifies diagnostic and therapeutic approaches predictive of favorable outcomes for patients with SCID.

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Data Availability

The data generated during the study are included in this published article and its supplementary file.

Code Availability

Not applicable.

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Funding

This work was supported by a grant from Marmara University Scientific Research Unit (SAG-C-TUP-250919–0288).

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Authors and Affiliations

  1. Faculty of Medicine, Division of Pediatric Allergy and Immunology, Marmara University, Fevzi Çakmak Mah. No: 41, Pendik, Istanbul, Turkey

    Elif Ozturk, Mehmet Cihangir Catak, Dilek Baser, Sevgi Bilgic Eltan, Nurhan Kasap, Ercan Nain, Alper Bulutoglu, Gamze Akgun, Yasemin Can, Asena Pinar Sefer, Royala Babayeva, Ahmet Ozen, Elif Karakoc-Aydiner & Safa Baris

  2. Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey

    Elif Ozturk, Mehmet Cihangir Catak, Dilek Baser, Sevgi Bilgic Eltan, Nurhan Kasap, Ercan Nain, Alper Bulutoglu, Gamze Akgun, Yasemin Can, Asena Pinar Sefer, Royala Babayeva, Ahmet Ozen, Elif Karakoc-Aydiner & Safa Baris

  3. Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Ayca Kiykim

  4. Pediatric Bone Marrow Transplantation Unit, Medical Park Goztepe Hospital, Istanbul, Turkey

    Koray Yalcin, Gulsun Tezcan Karasu & Akif Yesilipek

  5. Division of Pediatric Hematology, Umraniye Education and Research Hospital, University of Health Sciences, Istanbul, Turkey

    Suar Caki-Kilic

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  1. Elif Ozturk
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Contributions

S.B. and E.O. conceptualized and supervised the study. D.B., M.C.C., A.B., G.A., and Y.C. performed the experiments. A.K., S.B.E, N.K., E.N., A.P.S., R.B., A.O., E.K.A., and S.B. provided patient care and collected samples and clinical data. K.Y., S.K., G.T.K., and A.Y. performed transplantation of the patients. S.B. and E.O. wrote the paper. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Safa Baris.

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Ethics Approval

The study was approved by the Ethics Committee of Marmara University, School of Medicine (09.2019.511).

Consent to Participate

Informed consent for participation was obtained from all individuals.

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Informed publication consent was obtained from all participants.

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The authors declare no competing interests.

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The original online version of this article was revised due to 2 errors detected in Supplementary Table 2.

Supplementary Information

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10875_2022_1262_MOESM1_ESM.pdf

Figure S1. Immune recovery mostly observed in T followed by B cells, with the highest values in SCID patients. (A) Immune recovery rate of CD3+ T, CD4+ T and CD19+ B cells over time in SCID. (B) Immune recovery rate of CD3+ T, CD4+ T and CD19+ B cells over time in Omenn. (C) Immune recovery rate of CD3+ T, CD4+ T and CD19+ B cells over time in atypical SCID. (PDF 65 KB)

10875_2022_1262_MOESM2_ESM.pdf

Figure S2. The non-RAG patients and transplantation from peripheral blood demonstrate superior CD4+ T-cell recovery. The t-SNE heatmap analysis of T-cell subtypes in terms of mutation types (A) and stem cell sources (B). The equal selected event count of CD3+ T-cell population was accepted as control and displayed with 1 point. The event counts of the other populations were quantified in folding ratio as divided to CD3+ T-cell population. Cytobank software (Beckman Coulter) was used to analyze the available pre-and post-transplantation samples with Navios Ex cytometer. (PDF 203 KB)

10875_2022_1262_MOESM3_ESM.pdf

Figure S3. The T-cell subsets according to the CD4+ T-cell recovery rates revealed better normalized cellular profiles after transplantation in patients with high CD4+ T cells. The t-SNE heatmap analysis showing the comparisons between healthy controls and patients (A and B). The equal selected event count of CD45+ lymphocyte population was accepted as control and displayed with 1 point. The event counts of the other populations were quantified in folding ratio as divided to CD45+ lymphocyte population. ****p < 0.0001, *p < .05, 1-Way ANOVA with Tukey’s post hoc test. Cytobank software (Beckman Coulter) was used to analyze the available pre-and post-transplantation samples with Navios Ex cytometer. (PDF 237 KB)

10875_2022_1262_MOESM4_ESM.pdf

Figure S4. Gender matched transplantation and transplantation from peripheral blood display higher CD19+ B-cell recovery. The t-SNE heatmap analysis of B-cell subtypes in terms of gender matched transplantation (A) and stem cell sources (B). The analysis showing the comparisons between healthy controls and patients. The equal selected event count of CD45+ lymphocyte population was accepted as control and displayed with 1 point. The event counts of the other populations were quantified in folding ratio as divided to CD45+ lymphocyte population. Cytobank software (Beckman Coulter) was used to analyze the available pre-and post-transplantation samples with Navios Ex cytometer. (PDF 196 KB)

Supplementary file5 (DOCX 17 KB)

Supplementary file6 (DOCX 21.8 KB)

Supplementary file7 (DOCX 17 KB)

Supplementary file8 (DOCX 22 KB)

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Ozturk, E., Catak, M.C., Kiykim, A. et al. Clinical and Laboratory Factors Affecting the Prognosis of Severe Combined Immunodeficiency. J Clin Immunol 42, 1036–1050 (2022). https://doi.org/10.1007/s10875-022-01262-0

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