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Erschienen in:

01.01.2024 | Original Article

Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome

verfasst von: Sevgi Bilgic Eltan, Ercan Nain, Mehmet Cihangir Catak, Ege Ezen, Asena Pınar Sefer, Nastaran Karimi, Ayca Kiykim, Burcu Kolukisa, Dilek Baser, Alper Bulutoglu, Nurhan Kasap, Melek Yorgun Altunbas, Ezgi Yalcin Gungoren, Yasemin Kendir Demirkol, Seyhan Kutlug, Gonca Hancioglu, Fatih Dilek, Alisan Yildiran, Ahmet Ozen, Elif Karakoc-Aydiner, Batu Erman, Safa Baris

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2024

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Abstract

Purpose

Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive combined immunodeficiency. The detailed immune responses are not explored widely. We investigated known and novel immune alterations in lymphocyte subpopulations and their association with clinical symptoms in a well-defined ICF cohort.

Methods

We recruited the clinical findings from twelve ICF1 and ICF2 patients. We performed detailed immunological evaluation, including lymphocyte subset analyses, upregulation, and proliferation of T cells. We also determined the frequency of circulating T follicular helper (cT_FH) and regulatory T (Treg) cells and their subtypes by flow cytometry.

Results

There were ten ICF1 and two ICF2 patients. We identified two novel homozygous missense mutations in the ZBTB24 gene. Respiratory tract infections were the most common recurrent infections among the patients. Gastrointestinal system (GIS) involvements were observed in seven patients. All patients received intravenous immunoglobulin replacement therapy and antibacterial prophylaxis; two died during the follow-up period. Immunologically, CD4⁺ T-cell counts, percentages of recent thymic emigrant T cells, and naive CD4⁺ T decreased in two, five, and four patients, respectively. Impaired T-cell proliferation and reduced CD25 upregulation were detected in all patients. These changes were more prominent in CD8⁺ T cells. GIS involvements negatively correlated with CD3⁺ T-, CD3⁺CD4⁺ T-, CD16⁺CD56⁺ NK-cell counts, and CD4⁺/CD8⁺ T-cell ratios. Further, we observed expanded cT_FH cells and reduced Treg and follicular regulatory T cells with a skewing to a T_H2-like phenotype in all tested subpopulations.

Conclusion

The ICF syndrome encompasses various manifestations affecting multiple end organs. Perturbed T-cell responses with increased cT_FH and decreased Treg cells may provide further insight into the immune aberrations observed in ICF syndrome.

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Titel: Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome
verfasst von: Sevgi Bilgic Eltan
Ercan Nain
Mehmet Cihangir Catak
Ege Ezen
Asena Pınar Sefer
Nastaran Karimi
Ayca Kiykim
Burcu Kolukisa
Dilek Baser
Alper Bulutoglu
Nurhan Kasap
Melek Yorgun Altunbas
Ezgi Yalcin Gungoren
Yasemin Kendir Demirkol
Seyhan Kutlug
Gonca Hancioglu
Fatih Dilek
Alisan Yildiran
Ahmet Ozen
Elif Karakoc-Aydiner
Batu Erman
Safa Baris
Publikationsdatum: 01.01.2024
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 1/2024
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-023-01620-6

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Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome