Background/Aim: Neuropathic pain is a complex condition with an incompletely understood pathogenesis, and immunologic mechanisms are increasingly recognized as important contributors. This study aimed to evaluate the association between immunologic marker levels and the development of postherpetic neuralgia in patients with acute herpes zoster, with a particular focus on the impact of diabetes mellitus. Methods: In this prospective observational study, 20 patients with acute herpes zoster and a Douleur Neuropathique 4 score of 4 or higher were enrolled. Patients were categorized into two groups: those with diabetes mellitus (Group I, n = 10) and those without diabetes mellitus (Group II, n = 10). Routine laboratory parameters, including hemogram, C-reactive protein, erythrocyte sedimentation rate, fasting blood glucose, and hemoglobin A1c, were recorded. Immunologic markers, including CD3+, CD4+, CD8+, FOXP3+ regulatory T cells, natural killer cell subsets (regulatory, defective, cytotoxic, CD56 bright, and CD56 dim), and NK CD57, were analyzed at baseline and at month 3. Results: NK defective subset levels were lower in Group I than in Group II at baseline and at month 3 (P = 0.028 and P = 0.037, respectively). During follow-up, significant reductions in CD3+, CD4+, and CD8+ levels were observed in Group I (P = 0.013, P = 0.017, and P = 0.041, respectively), whereas significant decreases in NK defective and NK regulatory subsets were identified in Group II (P = 0.037 and P = 0.047, respectively). At the 3-month assessment, all patients met the study definition of postherpetic neuralgia. Conclusion: Diabetes mellitus was associated with alterations in natural killer cell subpopulations, suggesting impaired innate immune function in patients with acute herpes zoster. However, within the limitations of this small cohort, diabetes mellitus did not appear to independently increase the risk of postherpetic neuralgia. Larger, well-designed studies are needed to clarify the predictive role of immunologic markers in chronic neuropathic pain outcomes.

Hypomorphic DCLRE1C variants impair T and B cell development, leading to combined immunodeficiency (CID) or leaky severe combined immunodeficiency (SCID). Current treatment options, such as allogeneic hematopoietic stem cell transplantation (aHSCT), are associated with significant risks, highlighting the need for alternative therapeutic strategies. In this study, we report the first a proof-of-concept CRISPR-Cas9–mediated correction of a hypomorphic DCLRE1C variant (c.194 C > T; p.T65I) in CD4 + helper T (Th) cells using CRISPR-Cas9 gene-editing technology. CD4 + Th cells were isolated, and the variant region was edited with sgRNA and donor DNA. Gene editing efficiency was confirmed by Sanger sequencing, revealing successful restoration of the target region to its wild-type sequence. Functional analyses showed a significant increase in CD25 activation and Artemis protein expression post-editing, although DCLRE1C mRNA levels remained unchanged. The approximately 6–8

BACKGROUND:POLD1 defect with immunodeficiency is characterized by T-cell and NK-cell lymphopenia, with the patients having a higher susceptibility to herpetic and viral respiratory tract infections. Patients considered for HSCT may be at increased risk of regimen-related toxicity due to impaired DNA repair. Here, we describe the first case of successful HSCT in a patient with POLD1 deficiency who presented at a relatively older age for immunodeficiency and underwent HSCT despite concerns about DNA-related toxicity from the conditioning regimen. METHODS:We report the first successful HSCT in an 18-year-old woman with POLD1 deficiency who had recurrent pulmonary infections and shingles, and who was IgRT-dependent. The decision was made to perform HSCT from her matched related donor after informing the family that there was a concern about DNA-related toxicity following the HSCT procedure. RESULTS:She underwent HSCT from a matched related donor using a reduced-intensity regimen (cyclophosphamide, fludarabine, ATG) with bone marrow and peripheral blood as stem cell sources. GVHD prophylaxis included tacrolimus and low-dose methotrexate. Engraftment occurred promptly, without major complications. Post-HSCT follow-up demonstrated improved T-cell counts and function, and the patient remained well without IgRT. CONCLUSION:This first report of HSCT in POLD1 deficiency shows that reduced-intensity conditioning can achieve engraftment with minimal toxicity, supporting HSCT as a feasible option for these patients. The success of HSCT will be understood more clearly as the cases are presented.

Pathogenic variants in the T-cell receptor alpha constant (TRAC) gene have been primarily associated with combined immunodeficiency (CID). To date, only five patients from three unrelated families harboring the same TRAC variant with a CID phenotype, and three patients carrying a distinct variant with severe combined immunodeficiency (SCID), have been described. We report a previously unreported homozygous TRAC variant causing a premature stop codon in three siblings with classical SCID phenotype. Comprehensive immunological and molecular analyses were performed, including lymphocyte immunophenotyping, proliferation assays, qPCR for T helper (Th) subset–related gene expression, and cytokine secretion profiling. In silico analyses included conservation assessment, structural modeling using ChimeraX, and protein stability prediction via PremPS to evaluate the variant’s structural and functional consequences. All three siblings exhibited recurrent infections, refractory diarrhea, and elevated liver enzymes, accompanied by profound T-cell lymphopenia with preserved B-cell numbers. Whole-exome sequencing revealed a homozygous TRAC variant in the affected siblings and heterozygous carriage in their parents. The variant alters a highly conserved residue, disrupting hydrogen bonding and likely destabilizing the protein structure. Functional assays demonstrated a marked reduction in recent thymic emigrants (RTEs) cell ratio absence of TCRαβ⁺ T cells, skewed Th polarization, and elevated proinflammatory cytokine levelsfindings consistent with a SCID phenotype. These findings expand the clinical and molecular spectrum of TRAC-related immunodeficiency and support its inclusion among genes primarily associated with SCID. The results further emphasize that specific mutation sites within immune-related genes critically influence disease severity and phenotype variability.

Background/aim:CD20 deficiency is an autosomal recessive inborn error of immunity (IEI), and the only known affected individual worldwide has been under follow-up in our clinic. Because the consanguineous parents of the index patient are putative carriers, we hypothesized that additional individuals with reduced CD20 expression might exist within their village population. This study aimed to evaluate clinical features associated with IEI and to identify individuals displaying CD20 mean fluorescence intensity (MFI) patterns consistent with putative carrier status, while also providing appropriate genetic counseling. Materials and methods:This cross-sectional screening study was conducted in December 2024 in Çukurbağ village. Participants completed a questionnaire that included IEI warning signs and information about their familial relationship to the index case. CD19 and CD20 expression in peripheral blood samples was analyzed by flow cytometry. Individuals were classified as putative carriers if their CD20 MFI values were <50% of those of healthy controls. Results:A total of 145 individuals (44 children, 101 adults) from 52 families were screened. Among individuals related to the index case, the consanguinity rate was 39.3%. Jeffrey Modell Foundation scores were significantly higher in children than in adults (p < 0.05). No individuals with CD20 deficiency were identified. Approximately 10% of participants (n = 14) exhibited normal CD19 and CD20 percentages but showed reduced CD20 MFI values consistent with putative carrier status. All putative carriers were relatives of the index case. The proposed CD20-A700 (≤2537) and CD20-FITC (≤7787) MFI thresholds demonstrated high diagnostic performance (sensitivity and specificity values are presented for both parameters). Conclusion:CD20 MFI, rather than CD20 percentage, appears to be a more informative indicator for identifying individuals with flow-cytometric patterns suggestive of putative carrier status. Flow cytometry may serve as a rapid and practical preliminary screening tool in community-based settings; however, confirmation of carrier status requires molecular genetic testing, and genetic counseling should be based on verified genotypic results.

Purpose:Postherpetic neuralgia (PHN) is one of the most debilitating complications of herpes zoster and represents a major cause of chronic neuropathic pain. Increasing evidence suggests that immune dysregulation plays a critical role in neuropathic pain development. This study aimed to investigate the effects of the erector spinae plane (ESP) block on PHN development and immunological marker levels in herpes zoster patients who did not respond to pregabalin therapy. Patients and Methods:This prospective, controlled, single‑blind, non-randomized study included 30 patients with herpes zoster. Pregabalin therapy was initiated in all patients. Patients whose pain was adequately controlled with pregabalin were assigned to Group I, whereas patients with insufficient pain control received an ESP block and were assigned to Group II. Blood samples were collected at baseline, after treatment response, and at the three-month follow-up. T‑cell subsets and natural killer (NK) cell subgroups were analyzed using flow cytometry. Pain intensity, sleep interference, and PHN incidence were evaluated during follow-up. Results:Pain and sleep interference scores improved significantly over time in both groups (P < 0.05).The incidence of PHN did not differ significantly between the groups. However, at the three-month follow-up, patients in the ESP block group, who were receiving higher pregabalin doses, demonstrated lower CD3⁺ and CD4⁺ T-cell levels and reduced NK cell subset levels compared with Group I (P < 0.05).Baseline NK CD56 Bright levels were significantly higher in patients who did not develop PHN (P < 0.05). Conclusion:Although the ESP block did not reduce the incidence of PHN, immunological differences were observed between the treatment groups during follow-up. Higher baseline NK CD56 Bright levels in patients who did not develop PHN suggest a potential protective association between preserved NK-cell-mediated immunity and resistance to pain chronification following herpes zoster.

To compare the clinical, laboratory, and treatment characteristics of classical, common variable immunodeficiency (CVID)-related, and syndromic agammaglobulinemia in children with profound hypogammaglobulinemia. We retrospectively reviewed 25 children with profound hypogammaglobulinemia evaluated between 2005 and 2023. Patients were classified as classical (G1), CVID-related (G2a), or syndromic (G2b) agammaglobulinemia, and their clinical presentation, laboratory findings, and treatment outcomes were compared. Of the 25 children, 20 (80

BackgroundThe majority of monogenic inborn errors of immunity presenting as actinopathies were reported originally from the Middle East and North Africa (MENA) countries indicating a high prevalence of these entities in the region. However, their prognosis is unclear due to rarity and lack of comprehensive treatment outcomes.MethodsWe evaluated clinical, immunological, and genetic abnormalities associated with 15 genetic entities of actinopathies. Based on the function of mutant genes in actin-regulatory pathways, patients were classified into CDC42- and RAC2-related subcategories.ResultsA total of 503 individuals (29.5% females) from 17 countries were considered with a median age of 120 months. Although most patients presented initially with allergic phenotypes (37.7%), the most prevalent manifestations throughout the lifespan were infection in respiratory tracts (72.2%). Primary clinical diagnosis was mainly combined immunodeficiencies (48.3%) and the majority of cases were molecularly assigned to the CDC42 pathway (64.8%). The most common genetic defects were reported within the DOCK8 (n = 209) followed by the WAS (n = 94) and the CARMIL2 (n = 15) genes. Hematopoietic stem cell transplantation (HSCT) was conducted on 24.0% of patients, which significantly improved survival in patients with defects in WAS, DOCK8 and DOCK2. Overall mortality was 23.0%, mainly due to sepsis and malignancy.ConclusionPatients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.

Variants of uncertain significance (VUS) represent a major diagnostic challenge in the interpretation of genetic testing results, particularly in the context of inborn errors of immunity such as severe combined immunodeficiency (SCID). The inconsistency among computational prediction tools often necessitates expensive and time-consuming wet-lab analyses. This study aimed to develop disease-specific, multi-class machine learning models using in silico scores to classify SCID-associated genetic variants and improve the interpretation of VUS. Genes associated with SCID were identified based on the 2024 update of the International Union of Immunological Societies. Missense variants were retrieved from ClinVar and labeled as benign, likely benign, likely pathogenic, or pathogenic. Variants classified as VUS or with conflicting interpretations were excluded. In silico functional prediction scores were collected for each variant. Multi-class classification models were developed using six machine learning algorithms: Random Forest, XGBoost, Gradient Boosting, AdaBoost, Support Vector Machine and Logistic Regression. Performance was evaluated using five-fold cross-validation with five repeats (25 folds). A total of 537 variants from 71 genes were included in the final dataset. Among the models, Random Forest achieved the best performance with an accuracy of 0.70 ± 0.03 and the highest area under the receiver operating characteristic curve (AUROC: 0.90 ± 0.01). MetaRNN, BayesDel_addAF, and REVEL were the most predictive features. This study demonstrates that disease-specific, multi-class machine learning models leveraging in silico scores can effectively support the classification of SCID-related variants, offering a promising tool for improving VUS interpretation. Capsule Summary This study developed disease-specific multi-class machine learning models to classify SCID-related variants using in silico scores, with Random Forest showing the strongest performance in predicting variant pathogenicity.

Objective: Hypomorphic variants of DNA cross-link repair 1C (DCLRE1C) cause a spectrum of combined immunodeficiency phenotypes that range from mild autoimmunity to life-threatening malignancy. We aimed to integrate detailed clinical phenotyping with in silico pathogenicity metrics to improve the prediction of adverse outcomes in this rare disorder. Materials and Methods: We compiled a descriptive cohort of 41 patients carrying one of 12 published hypomorphic DCLRE1C variants. Inferential analyses focused on the molecularly homogeneous subgroup of 25 individuals harboring three recurrent missense changes within the metallo-beta-lactamase/beta-CASP domains-c.194C>T [p.Thr65Ile], c.500C>T [p.Thr167Met] and c.632G>T [p.Gly211Val]. Comprehensive clinical, immunological, and laboratory data were extracted. Pathogenicity was assessed with eight in silico algorithms, Delta Delta G stability modelling, and structural mapping. Logistic regression identified variables associated with malignancy and autoimmunity, and composite risk scores were generated. Results: Median age at last follow-up was 9.4 years (range 0.5-27). Recurrent sinopulmonary infection (80%), chronic diarrhea (48%), and candidiasis (44%) were common across variants, while otitis media and growth retardation were confined to c-terminal changes. All three analyzed variants exceeded pathogenicity thresholds (mean Combined Annotation-Dependent Depletion [CADD] 26.7 +/- 2.1) and reduced predicted protein stability (mean Delta Delta G +1.8 kcal/mol). A revised malignancy risk score (lymphadenopathy, immunoglobulin G [IgG] <400 mg/dL, diarrhea, Delta Delta G >= 1 kcal/mol, BayesDel >0.5, age > 60 months) > 4 achieved an area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval [CI] 0.57-1.00), with 75% sensitivity and 100% specificity. The analogous autoimmunity score (skin lesions, pulmonary infections, IgG low, Delta Delta G >= 1, BayesDel > 0.5, CD19 low, age > 60 months) > 8 showed moderate discrimination (AUC 0.75; 95% CI, 0.54-0.97), with 83.3% sensitivity and 73.7% specificity. Conclusion: Integration of domain-restricted in silico metrics with core clinical parameters modestly improves malignancy risk prediction in hypomorphic DCLRE1C deficiency. Prospective, multi-center validation and functional assays are required before clinical implementation.

Objective:CD19 is a cellular receptor belonging to the immunoglobulin (Ig) superfamily and serves as a critical signaling component in B-cells differentiation and activation. This study investigates gene expression changes in the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in patients with CD19 deficiency. The role of CD19 in B-cell function was explored, along with its potential impact on these signaling pathways and the overall immune response. Materials and Methods:RNA samples were obtained from three patients diagnosed with CD19 deficiency, as well as heterozygous carriers and healthy controls. Gene expression profiles related to the PI3K/AKT axis and NF-κB pathway were analyzed using quantitative polymerase chain reaction (PCR). Results:The study revealed significant alterations in the expression of signaling pathway components, including PI3K, phosphoinositide-3-kinase regulatory subunit 1 (p85), TNF receptor-associated factor 2 (TRAF2), forkhead box O1 (FOXO1), and NF-κB, in CD19-deficient patients. While PI3K and NF-κB expression were significantly downregulated in these patients, CD19, p85, FOXO1, and TRAF2 expression were markedly upregulated. These changes suggest impaired B-cell function, leading to weakened immune system responses. Conclusion:CD19 deficiency disrupts B-cell receptor signaling, resulting in significant alterations in the PI3K/AKT axis and NF-κB pathways. These disruptions impair B-cell maturation and survival, ultimately leading to compromised immune responses. This study provides the first detailed molecular insights into the effects of CD19 deficiency, enhancing our understanding of how these signaling pathways regulate immune function.

X-linked agammaglobulinemia (XLA) is caused by Bruton tyrosine kinase gene mutations, leading to B-cell deficiency. This study aimed to investigate myeloid-derived suppressor cells (MDSCs) frequency, lymphocyte apoptosis and clinical significance in patients with XLA. The study comprised 46 paediatric (mean age: 9.9 ± 4.8 years) and 21 adult patients (24.6 ± 5.9 years). Total MDSCs (HLA-DR-CD33+CD11b+) were subdivided into CD15+ polymorphonuclear (PMN-MDSCs) and CD14+ monocytic (M-MDSCs) and analysed by flow cytometry. The paediatric XLA patients had increased M-MDSCs and early apoptotic lymphocyte frequency compared to healthy subjects. The mean diagnostic delay was positively correlated with early apoptotic CD3+ and CD4+ T-cells. Seventeen patients (14 adults and 3 children) had bronchiectasis. PMN-MDSCs were higher in adult patients than in paediatric patients. Increased PMN-MDSCs in adults with XLA suggest the presence of chronic inflammation in patients with bronchiectasis. The study findings broaden understanding of XLA's complex immunopathology and highlight the need for more comprehensive immune monitoring of these patients beyond antibody production.

PURPOSE:Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are self-regenerative and able to differentiate into multipotent stem cells. There may be different sources of mesenchymal stem cells (MSCs) involved in the repair mechanism of damaged tissues in the organism. WJ-MSCs may differentiate into osteocytes, chondrocytes, adipocytes, and myocyte cells. Furthermore, MSCs show neuroprotective effects on neurons. Today, many MSC neuroregenerative treatments have been shown to be effective. Studies have shown that MSCs are more involved in paracrine effects due to their neuroprotective effect in multiple diseases such as multiple sclerosis, acute spinal cord injury and encephalomyelitis. The main aim of this study was to investigate the neuronal markers of stem cells after incubation with β-mercaptoethanol (BME). MATERIALS AND METHODS:In our study, WJ-MSCs were thawed in a water bath at 37°C and cultivated in cell culture dishes. When the cell occupancy rate reached 60-70%, they were treated with 2 mM BME. At the first and third hours, MSCs were removed from the dishes, and flow cytometry and immunostaining revealed that BME's nestin, neuron filament light (NF-L), SOX1, SOX2, doublecortin (DCX), glial fibrillary acidic protein (GFAP), Ki67, and CD44 were evaluated. RESULTS:Immunocytochemically, nestin and NF-L values ​​of MSCs exposed to BME increased at the first hour. In the flow cytometric evaluation, it was observed that nestin was high in the first hour. CONCLUSION:One of our aims in this study was to reduce the possible toxic side effects of BME for MSCs by exposing the BME used in previous studies at the minimum dose for neuronal differentiation. In our study, we showed first-hour changes similar to the neuronal differentiation obtained with pre- and post-induction in other studies.

BACKGROUND:In this study, we aimed to report long-term follow-up of our pediatric and adult patients with DCLRE1C (DNA cross-link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID). METHODS:Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls. RESULTS:Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B- and T-cell lymphopenia at the first admission. Recent thymic emigrants (RTE), Tnaive, Bnaive, CD56dimCD16+ cell ratios were significantly lower in the patients than in control; however, follicular helper T TFH and Th1 [interferon gamma (IFN-γ)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow-up times of transplant patients was 56 (9-67) months. CONCLUSION:Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1-dominant immune response before and after HSCT. Increased IFN-γ and TFH cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long-term follow-up of these patients after HSCT will help to better understand the disease and its pathophysiology.

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 (TBET, STAT1, STAT4), Th2 (GATA3, STAT6), Th17 (RORgt, STAT3), Treg (FoxP3, STAT5) transcription factors and the major cytokines of these cells (Th1; IFNG, Th2; IL4, Th17; IL17A-21-22, Treg; IL10, TGFβ) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients’ Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121–2 A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

PurposeThe measurement of T-cell receptor excision circle (TREC) is used for newborn screening (NBS) in dried blood spot (DBS) samples from Guthrie card for severe combined immunodeficiency (SCID). Here, we report the results of first newborn screening pilot program for SCID conducted in Türkiye.MethodsThe study was carried out together with Ankara University School of Medicine and The Ministry of Health, Public Health General Directorate, Pediatric and Adolescent Health Department. TREC measurements were performed in randomly selected Guthrie card samples obtained from 20253 babies born between October 2018 and October 2020. The TREC analyses were performed together with beta Actin (β-Actin) via RT-PCR (Real Time Polymerase Chain Reaction).ResultsTRECs found to be normal (≥15 copies/µl) in 98,6% of the newborns (n: 19975) but low (<15 copies/µl) in 1.4% (n:278) at the initial analyses. TRECs were retested in 278 suspected infants and found to be normal in 160 (0.8%) while low in 118 (0.58%). New DBS were obtained from the babies with low TRECs (new sample test). TRECs were normal in 108 (0.53%) of the new sample tests and low in 10 (0.049%). Two among 10 babies who had abnormal (undetectable) TRECs were diagnosed as SCID; ADA (P1) and RAG1 (P2) defects were confirmed respectively. They both received curative treatments [gene therapy (P1) and HSCT (P2)]. The remaining 6 of 8 newborns with abnormal TRECs were found normal after clinical and laboratory immune work-up, while medical records of other two revealed early postnatal death due to extreme prematurity.ConclusionIn the light of this study the incidence of SCID was detected at least 1/10000 live births in Türkiye. This study shows the feasibility and usefulness of initiating SCID screening in Türkiye.

OBJECTIVE:In this study, we explored the expression of transcription factors, cytokines, and co-stimulatory molecules within the helper T (Th) cell subsets (Th1, Th2, Th17, and Treg) of patients with hypomorphic DCLRE1C gene mutations. METHODS:The study comprised eight patients and five controls. Transcription factor and cytokine expressions of Th subsets and co-stimulatory molecules were investigated by qPCR and flow cytometric following T cell stimulation. The findings were compared between patients (non-HSCT) and with hematopoietic stem cell transplantation (HSCT). RESULTS:Flow cytometric analyses; while the Treg rate was significantly lower in non-HSCT than in controls (p = 0.010), the IFN-γ rate was significantly higher in patients than in the control and HSCT groups (p = 0.016, p = 0.022, respectively). Co-stimulatory molecule expressions were significantly lower in non-HSCT than in control (p < 0.001), and there was a significant improvement after HSCT. Post-stimulation qPCR analysis, significant changes were detected in non-HSCT/control, non-HSCT/HSCT, and HSCT/control comparisons. CONCLUSIONS:Our study is the first study to molecularly investigate Th cell subsets in hypomorphic DCLRE1C patients. It was determined that abnormalities in Th cell subsets still persisted despite HSCT. There are still many conditions to be explained in these patients, and we believe that our study may shed light on future studies.