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Insu cient dietary folate intake, hereditary malabsorption, or defects in folate metabolism may lead to combined immunode ciency (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 immunode ciency was lacking. We report two cousins carrying a homozygous pathogenic variant c.1042G>A, resulting in p.G348R substitution who showed symptoms of immunode ciency associated with defects of folate metabolism. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quanti ed 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 ow cytometric assays. Patients were treated with and bene ted from folinic acid (FA). 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 signi cantly reduced at sub-and supraoptimal folic 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 rst experimental evidence that loss of function mutations in SLC19A1 may present with symptoms of immunode ciency.

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Aims: The aim is to investigate the association of the osteoprotegerin (OPG)/ soluble(s) receptor activator nuclear kappa B ligand (RANKL) with the prognosis of children with acute lymphoblastic leukemia (ALL). Methods: Patients with the diagnosis of ALL between the years 2008-2010, were enrolled in the study. Demographic characteristics and complete blood count findings, treatment responses, as well as OPG and sRANKL levels were evaluated on admission and at the end of induction treatment. Results: Mean serum levels of OPG and sRANKL on admission were 38,6 ±19,03 ng/ml and 0,22±0,24 ng/ml, respectively. Whereas, at the end of induction, serum levels were measured as 35,5±40,8 ng/ml for OPG and 0,033±0,056 ng/ml for sRANKL. A statistically significant decrease was determined for sRANKL at the end of induction therapy, compared to admission (p:0,000). Conclusion: In the current research, OPG and sRANKL are increased at diagnosis of childhood B-ALL. Whereas, no significant relationship between the OPG and sRANKL levels and the disease prognosis was determined.

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