|3.||Advances in the Molecular Etiology of Severe Combined Immunodeficiency and Its Screening|
Ananya Mahapatra, Henu Kumar Verma, Sagorika Nag, SANTOSH Singh, Arunarun Khattri, LVKS Bhaskar
doi: 10.4274/tji.galenos.2023.29491 Pages 1 - 16
Severe combined immunodeficiency (SCID) is the most severe heterogeneous group of inherited disorders characterized by profound abnormalities such as humoral and cell-mediated immunity defects and hindered natural killer cell development and function. The knowledge of the molecular basis of SCID is essential for precise diagnosis and early treatment. In recent years, new genetic defects that cause SCID have been discovered, and the molecular and immunological mechanisms of SCID have been better understood. SCID symptoms include candidiasis, chronic diarrhea, failure to grow, and oral thrush. Hematopoietic stem cell transplantation, enzyme replacement therapy, and gene therapy are used to treat SCID. The prevalence of SCID varies worldwide. More than 80% of SCID infants have no family history of the condition. However, the development of a newborn screening test has enabled SCID detection before symptoms appear, ensuring that affected infants receive life-saving treatments. Countries that organize newborn screening programs for SCID can detect patients in their early stages of life and treat them accordingly. This review will serve as a source of up-to-date information on the identification of various genetic disorders that cause SCID, as well as their clinical characteristics, treatments, and diagnosis options, potentially saving the lives of many infants before pathogenic infections occur.
|4.||The CpG Island Methylation Status and mRNA Expression Level of CTLA4 in Childhood Hashimotos Thyroiditis|
Fatemeh Safari, Mohammad Hossein Ahmadi, Mehdi Azad, Neda Karami, Amirhosein Maali, Neda Mohammadi, Ali Homaei, Farshad Foroughi
doi: 10.4274/tji.galenos.2023.70883 Pages 17 - 22
Objective: Hashimotos thyroiditis (HT) is an autoimmune thyroid disease characterized by thyroid-specific autoantibodies. Recent studies have shown the critical footprint of DNA methylation in autoimmune diseases. The aberrant DNA methylation of CTLA4 has been previously reported in autoimmune thyroid diseases. This study aimed to investigate the methylation status of the CpG island of CTLA4 promoter and its mRNA expression level in HT patients.
Materials and Methods: In this case-control study, 45 HT patients (admitted to Qods Hospital, Qazvin, Iran) and 5 healthy individuals participated. After RNA and DNA extractions, the DNA methylation pattern of the CpG island of CTLA4 promoter and CTLA4 mRNA expression level were evaluated. All statistical analyses were performed using SPSS ver 20.
Results: Our results indicated partial hypermethylation status in the CpG island of CTLA4 promoter in HT patients compared to normal individuals, but this hypermethylation was not significantly higher (p=0.332). The mRNA expression level of CTLA4 was significantly decreased in HT patients compared to that of controls (Foldchange=0.31, p=0.015). Also, serum level of anti-TPO antibody was not significantly correlated with CTLA4 expression level and its methylation status.
Conclusion: Since the CTLA4 acts as an immune checkpoint that leads to the downregulation of immune response, partial hypermethylation and downregulation of CTLA4 may play a critical role in preventing switching off the immune response after a hyperactivation against the thyroid.
|5.||Immunohistochemical Evaluation of TNF-α, IL-1, IL-12, IL-17, IL-23 Expression and Investigation of the Effect of Demodex in Patients with Discoid Lupus Erythematosus|
Recep Dursun, Selami Aykut Temiz, Sıddıka Fındık, Koray Durmaz, Pembe Oltulu
doi: 10.4274/tji.galenos.2023.63626 Pages 23 - 28
Objective: Discoid lupus erythematosus (DLE) is a chronic inflammatory skin disease that can be triggered by several factors although its etiology is not yet known. Hypotheses have been reported that the demodex mites may be involved in the etiopathogenesis of DLE. In this study, we aimed to investigate the potential relationship between the frequency of immunohistochemical staining of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-12, IL-17 and IL-23 cytokines obtained from cutaneous biopsy of DLE patients and disease severity.
Materials and Methods: Biopsy tissues of patients who were previously diagnosed with DLE in the dermatology outpatient clinic, which were also supported histopathologically, were re-sectioned and subjected to immunohistochemical examination for TNF-α, IL-1, IL-12, IL-17 and IL-23, and their staining scores were obtained. These immunohistochemical staining scores were compared with disease severity. The presence and density of demodex were evaluated in standard skin surface biopsy taken from the lesions at the time of diagnosis.
Results: In the comparison of immunohistochemical staining scores with DLE-skin score (DLE-SS), a statistically significant positive correlation was found between DLE-SS and TNF-α (p=0.003), DLE-SS and IL-17 (p=0.002). There was no difference between the presence or absence of demodex and DLE-SS (p=0.9). There was no correlation between demodex density and disease severity in demodex-positive cases (p=0.34).
Conclusion: In line with the data obtained from our study, TNF-α and IL-17 seem to be more associated with the disease severity in DLE. The fact that demodex positivity/negativity and demodex density are independent of disease severity supports that demodex mite is an etiopathogenetic factor rather than overlap in DLE cases. Further studies on this subject are needed.
|6.||Classification of Common Variable Immunodeficiency Using Measurement of B-cell Subsets in Moroccan Patients|
Khaoula Mokhantar, Allaoui Abire, Fatima Ailal, Jalila El Bakkouri, Kaoutar Ouazahrou, Abderrahmane Errami, Ahmed Aziz Bousfiha, Mina Moudatir
doi: 10.4274/tji.galenos.2023.36854 Pages 29 - 36
Objective: Common variable immunodeficiency (CVID) is a complex inborn error of humoral immunity with complications of infectious and non-infectious origins. Classifications of CVID patients provide a clearer understanding of the pathogenesis, prediction, and management of non-infectious complications. This study aimed to classify Moroccan CVID patients using B-cell immunophenotyping, based on the European classification (EUROclass).
Materials and Methods: We recruited 20 CVID patients fullfilling established diagnostic standards. After collecting clinical and demographic data, we analyzed B-cell subsets by flow cytometry, grouped patients, and assessed the relationship of each group with clinical manifestations.
Results: In our cohort, 90% of the patients had a clinical history of respiratory infections. The non-infectious manifestations included splenomegaly, autoimmunity, lymphadenopathy, and granulomatous diseases diagnosed in 50%, 45%, 40%, and 25% of patients, respectively. We observed significant co-occurrence of splenomegaly with autoimmunity and to a lesser extent with granulomatous diseases. Patients had a significant reduction in total, switched memory, marginal zone-like, and plasmablasts, along with a strong increase in the percentage of activated B-cells, suggesting a defect in the late phases of B-cell differentiation. This condition was linked with an increased occurrence of splenomegaly and granulomatous affections. Besides, patients had also an expansion of CD21low B-cells, which was strongly associated with splenomegaly.
Conclusion: The classification of the first Moroccan cohort of CVID patients showed agreement with previous results. It suggests the possibility of adopting this approach on a global scale for better diagnosis and follow-up of CVID patients.
|7.||Effects of Hyperbaric Oxygen on Anti-dsDNA Antibodies and IL-6 in BALB/c Mice with Pristane-Induced Lupus Nephritis|
Indri Dwi Murbani, Titut Harnanik, Soetjipto Soetjipto
doi: 10.4274/tji.galenos.2023.78942 Pages 37 - 41
Objective: Lupus nephritis (LN) has negative outcomes in patients. It is associated with enhanced oxidative stress. The aim in this study was to explore whether hyperbaric oxygen (HBO) made beneficial effects on the levels of anti-double stranded DNA (dsDNA) antibodies and interleukin-6 (IL-6) within the serum of LN mode treated with HBO compared to LN mode without HBO and negative controls.
Materials and Methods: The samples were separated into 3 groups (negative control, LN and LN + HBO groups) in 24 mice. Pristane was injected into female BALB/c mice to make the LN model. After 60 days, HBO therapy was administered to the LN model for 10 sessions. Levels of anti-dsDNA antibodies and IL-6 serum of all groups were examined by ELISA.
Results: The level of anti-dsDNA antibodies and IL-6, as the biomarker of LN activity, was essentially diminished within HBO [a statistically significant decrease (p<0.050) between the LN + HBO group and LN group].
Conclusion: The inflammation in LN can be reduced by decreasing anti-dsDNA antibodies and IL-6 levels with HBO through the repairment of hypoxia.