Immunodeficiency associated with a novel functionally defective variant of SLC19A1 benefits from folinic acid treatment
Yazarlar (15)
Veysel Gök Türkiye
Dr. Öğr. Üyesi Şerife ERDEM Türkiye
Yeşim Haliloğlu
Atıl Bişgin
Türkiye
Türkiye
Kemal Erdem Başaran Türkiye
Mehmed Fatih Canatan
Alper Özcan Türkiye
Ebru Yılmaz Türkiye
Can Acıpayam Kahramanmaraş Sütçü İmam Üniversitesi, Türkiye
Musa Karakükcü Türkiye
Halit Canatan Türkiye
Hüseyin Per Türkiye
Türkan Patıroğlu
Türkiye
Türkiye
Ahmet Eken Türkiye
Ekrem Ünal Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | Springer Science and Business Media LLC (Q1) | ||
| Dergi ISSN | 1466-4879 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 02-2023 |
| Cilt / Sayı / Sayfa | 24 / 1 / 12–20 | DOI | 10.1038/s41435-022-00191-7 |
| Makale Linki | http://dx.doi.org/10.1038/s41435-022-00191-7 | ||
| Özet |
| Insufficient dietary folate intake, hereditary malabsorption, or defects in folate transport may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. We report two cousins carrying a homozygous pathogenic variant c.1042 G > A, resulting in p.G348R substitution who showed symptoms of immunodeficiency associated with defects of folate transport. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Patients were treated with and benefited from folinic acid. Studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at suboptimal folic acid and supraoptimal folinic acid concentrations. In addition, patients' PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1. This study presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that functionally defective variants of SLC19A1 may present with symptoms of immunodeficiency. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 5 |