Real-world patient data on immunity and COVID-19 status of patients with MPS, Gaucher, and Pompe diseases from Turkey.

BACKGROUND: COVID-19 and lysosomal storage disorders (LSDs) share a common immunological pathway as they cause the release of cytokines in a similar pattern. We aimed to evaluate the immunity status and reveal the course of COVID-19 in patients with LSDs. RESULTS: The median age of 110 patients with LSDs was 129 months (range: 21-655), and all but one patient with mucopolysaccharidosis (MPS) type III were regularly receiving enzyme replacement therapy (ERT). In 53.6% (n = 56) of the patients (23 patients with Gaucher disease [10 type III, 13 type I], 26 patients with MPS [8 type VI, 11 type IVA, 1 type III, 3 type II, and 3 type I], and 7 patients with Pompe disease), an abnormality in at least one of the autoimmunity or immunodeficiency parameters was reported. Furthermore, 12 (57%) of 21 Gaucher cases (7 type III, 5 type I), 18 (40.9%) of 44 MPS cases (9 type IVA, 5 type VI, 1 type I, 2 type II, and 1 type III), and six (66%) of nine Pompe cases were reported to involve abnormalities in at least one of the parameters related to immunodeficiency. Immunoglobulin (Ig) M and IgA levels were reported to be lower, and there were abnormalities in the lymphocyte counts and subgroups in the MPS group. ANA was reported to be positive in one patient with Gaucher type III, anti-DNA in two patients with Gaucher type I and one patient with MPS type VI, antithyroglobulin in two patients with Gaucher type I, anti-TPO in one patient with Gaucher type I, TRAB in one patient with Gaucher type I, antiphospholipid IgM in three patients with Gaucher type III and one patient with Gaucher type I, anticardiolipin IgM in one patient with Gaucher type I, one patient with Gaucher type III, and one patient with MPS type II. However, no clinical presentation was consistent with the laboratory results except for one patient with Gaucher type I disease with Hashimoto thyroiditis. Two of the four patients who survived the COVID-19 infection with mild symptoms had a diagnosis of Gaucher type I, and no abnormality was detected in their laboratory tests. The other two patients had a diagnosis of MPS types VI and II. Immune dysfunction was detected in the patient with a diagnosis of MPS type II. Four of our patients were discharged without any sequelae. CONCLUSION: Problems with immunity did not cause any noticeable clinical results. Being well protected by reducing social contact might have played a role. However, we believe that it should be borne in mind that cardiac and pulmonary involvement, as well as immune dysfunction in LSDs, may cause an increased need for intensive care because of secondary bacterial infections.

Results of Liquid Biopsy Studies by Next Generation Sequencing in Patients with Advanced Stage Non-small Cell Lung Cancer: Single Center Experience from Turkey.

Several studies demonstrated the utility of plasma-based cell-free circulating tumor DNA (ccfDNA) in determination of mutations in non-small cell lung cancer (NSCLC). We aimed to report our results of next generation sequencing (NGS) using liquid biopsy in patients with NSCLC. Patients with advanced stage NSCLC were enrolled and their genomic profiling results were recorded. Next generation sequencing targeted panel includes 19 hot-spot genes. The plasma was separated from the peripheral blood sample and ccfDNAs were isolated for NGS. We performed genomic profiling in 100 patients (20 females and 80 males) with a median age of 59.3 (range 26-79). A second liquid biopsy was performed in eight patients who developed progressive disease after the first treatment. The study population had adenocarcinoma (AC) (n = 73), squamous cell carcinoma (SCC) (n = 14), or NSCLC-NOS (not otherwise specified) (n = 13). In the SCC group, three of 14 patients had variants on EGFR and MET genes. In the AC and NSCLC-NOS groups, 39 out of 86 patients (45.3%) had variants. The most common one was in the EGFR gene (n = 27, 31.4%) including seven mutations related to drug resistance and two were polymorphisms. Three patients had both driver and resistance mutations (EGFR T790M, n = 2; KRAS exon 2 G12S and MET exon 14 E1012K, n = 1). Fifteen patients (17.4%) had an activating EGFR mutation and eight patients (9.3%) had variants in the KRAS gene. We reported our results regarding genomic profiling related to treatment using liquid biopsy in patients with NSCLC. Advantages of this method are the non invasiveness and reproducibility.

Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. METHODS: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. RESULTS: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. CONCLUSIONS: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

Serum soluble tumour necrosis factor related apoptosis-inducing ligand level and peripheral eosinophil count in patients with nasal polyposis.

BACKGROUND: Nasal polyposis is one of the most common inflammatory pathologies of the nasal cavity. Eosinophilic inflammation plays an important role in the pathogenesis. This study aimed to investigate soluble tumour necrosis factor related apoptosis-inducing ligand levels and eosinophil count in nasal polyposis patients. METHODS: The study was performed on 24 adult nasal polyposis patients and 24 age-matched healthy individuals. The patients had not received any medical or surgical treatment. Pre-operative computed tomography scans were assessed using the Lund-MacKay grading system, and soluble tumour necrosis factor related apoptosis-inducing ligand levels were measured with a sandwich enzyme-linked immunosorbent assay. RESULTS: Compared with controls, eosinophil levels in nasal polyposis patients were increased (p = 0.024), but there was no significant difference in soluble tumour necrosis factor related apoptosis-inducing ligand levels (p = 0.529). The Lund-MacKay mean grading was 12.43 ± 6.9. There was no correlation between soluble tumour necrosis factor related apoptosis-inducing ligand level and Lund-MacKay grading and eosinophil count. CONCLUSION: There was no relationship between soluble tumour necrosis factor related apoptosis-inducing ligand level and blood eosinophil or clinical markers; however, soluble tumour necrosis factor related apoptosis-inducing ligand level remains of interest for future studies.

Circulating soluble tumor necrosis factor related apoptosis inducing-ligand (TRAIL) is decreased in type-2 newly diagnosed, non-drug using diabetic patients.

We examined the association between serum sTRAIL measured by ELISA and HbA1C levels, pre/post-prandial blood glucose levels and body mass index in 22 newly diagnosed type-2 diabetic patients. A significant difference in sTRAIL levels was found between study group and controls.

Concurrent gene therapy strategies effectively destroy synoviocytes of patients with rheumatoid arthritis.

Objectives. Rheumatoid arthritis (RA) is characterized by the chronic inflammation of the synovial joints resulting from the hyperplasia of synovial cells and the infiltration of lymphocytes, macrophages and plasma cells. Currently, the aetiology of RA is not known, and new treatment modalities are needed to prevent the disease progression. Apoptosis induction of synovial cells through the use of death ligands has been explored as a treatment modality for RA. Thus, the primary objective of this study was the testing of the efficacy of adenovirus delivery of human TRAIL (Ad5hTRAIL) for the treatment of patients with RA. Methods. Primary synovial cell cultures were established from eight patients with RA. Adenovirus permissiveness of synovial cells was determined by the infection of synoviocytes with adenovirus vector encoding green fluorescent protein (AdEGFP). TRAIL sensitivity of synoviocytes was assessed through the infection with Ad5hTRAIL vector using Live/Death Cellular Viability/Toxicity kit from Molecular Probe. TRAIL receptor profiles of synoviocytes were revealed by real-time RT-PCR assays followed by flow cytometric analyses. Results. While the presence of TRAIL death receptors were necessary for the induction of cell death, high levels of TRAIL-R4 decoy receptor expression on surface were correlated with TRAIL resistance. A DcR2 siRNA approach in combination with Ad5hTRAIL infection eliminated apoptosis-resistant RA synovial fibroblasts. Conclusion. Because a DcR2 siRNA approach in combination with Ad5hTRAIL infection exterminated RA synoviocytes to a greater extent than Ad5hTRAIL alone, the modulation of TRAIL receptor expression might be a new gene therapy strategy to sensitize RA synoviocytes to TRAIL.