ImmunoTargets and Therapy最新文献

{"title":"Selinexor Synergistically Promotes the Antileukemia Activity of Venetoclax in Acute Myeloid Leukemia by Inhibiting Glycolytic Function and Downregulating the Expression of DNA Replication Genes.","authors":"Jiqian Jiang, Yan Wang, Dan Liu, Xiaoyu Wang, Yingqiao Zhu, Juan Tong, Erling Chen, Lei Xue, Na Zhao, Tingting Liang, Changcheng Zheng","doi":"10.2147/ITT.S429402","DOIUrl":"https://doi.org/10.2147/ITT.S429402","url":null,"abstract":"<p><strong>Introduction: </strong>The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear.</p><p><strong>Methods and results: </strong>Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination.</p><p><strong>Conclusion: </strong>This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"135-147"},"PeriodicalIF":7.2,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Chemotherapy versus Chemotherapy Alone in Non-Small Cell Lung Cancer: A Propensity Score and Inverse Probability Treatment Weighting Analysis","authors":"Junfeng Zhao, Shaoyu Hao, Ying Li, Xiaoman Liu, Zhaoxuan Liu, Chunhui Zheng, Dan Han","doi":"10.2147/itt.s437911","DOIUrl":"https://doi.org/10.2147/itt.s437911","url":null,"abstract":"Purpose: This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy (NCT) and neoadjuvant immunotherapy combined with chemotherapy (NICT) combined with radical lung cancer resection for the treatment of patients with resectable non-small cell lung cancer (NSCLC). To adjust for confounding factors, we innovatively adopted two matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). Patients and Methods: We conducted a retrospective analysis of the clinicopathological features and prognosis of patients with resectable NSCLC treated with NCT or NICT combined with radical lung cancer resection using propensity score matching (PSM) at a ratio of 1:1 and IPTW to balance potential bias. Results: After PSM, 116 pairs of patients who had undergone NCT or NICT were selected for the final analysis. The pathological complete remission (pCR) and major pathological remission (MPR) rates were significantly better in the NICT group than in the NCT group (pCR rate of 44.8% vs 2.6%, P < 0.001; MPR rate of 66.4% vs 20.7%, P < 0.001). No significant difference was seen between the NICT and NCT groups in terms of postoperative complications (12.1% vs 9.5%, P =0.182). Patients in the NICT group had significantly better disease-free survival (DFS) and overall survival(OS) than those in the NCT group ([3-year DFS: 75.2% vs 43.3%, P < 0.001] and [3-year OS: 91.5% vs 58.0%, P < 0.001]). Among all patients, those with postoperative pathology of pCR had better DFS ( P < 0.001) and OS ( P = 0.009). Patients with postoperative pathology of MPR had better DFS ( P < 0.001) and OS ( P < 0.001). The IPTW method yielded similar pathologic and prognostic results. Conclusion: Patients with resectable NSCLC treated with NICT had better pathological responses and prognosis, than those treated with NCT, and the safety profiles of NICT and NCT were similar. Keywords: neoadjuvant immunotherapy, neoadjuvant chemotherapy, non-small cell lung cancer, propensity score matching, inverse probability of treatment weighting, lung cancer resection, immune checkpoint inhibitor","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"16 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135664808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Globoid Cell Leukodystrophy (Krabbe Disease): An Update.","authors":"Azzam A Maghazachi","doi":"10.2147/ITT.S424622","DOIUrl":"https://doi.org/10.2147/ITT.S424622","url":null,"abstract":"<p><p>Globoid cell leukodystrophy or Krabbe is a disease that affects children as well as adults who have mutations in the gene encoding the enzyme galactosylceramidase/galctocerebrosidase (GALC), resulting in the deposition of the toxic lipid D-galactosyl-beta1-1' sphingosine (GalSph or psychosine). Several therapeutic modalities were used to treat patients with Krabbe disease, including hematopoietic stem cell transplantation, enzyme replacement therapy, autophagy activators, intravenous immunoglobulin, and inhibitors of the Pyroptosis process, among many other approaches. In this article, I will briefly discuss the disease in both human and animal model, describe recent clinical observations as well as methods utilizing genetic analysis for diagnosis, and finally review recent advances in treating this rare and devastating disease.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"105-111"},"PeriodicalIF":7.2,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Immune Targets for Type 1 Diabetes and Latent Autoimmune Disease Immunotherapy.","authors":"Khalid Siddiqui,&nbsp;Shaik Sarfaraz Nawaz","doi":"10.2147/ITT.S417917","DOIUrl":"10.2147/ITT.S417917","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is an autoimmune disease that destroys pancreatic beta cells, which produce insulin in the islets of Langerhans. The risk of developing T1D is influenced by environmental factors, genetics, and autoantibodies. Latent autoimmune diabetes in adults (LADA) is a type of T1D that is genetically and phenotypically distinct from classic T1D. This review summarizes the accumulated information on the risk factors for T1D and LADA, and immunotherapy trials that offer insights into potential future combined therapeutic interventions for both T1D and LADA to slow the rate of islet cell loss and preserve beta cell function. Future research should also focus on improving intervention doses, conducting more thorough examinations of intervention responders, and/or combining minimally effective single-target immunotherapies to slow the rate of islet cell loss and preserve beta cell function.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"91-103"},"PeriodicalIF":7.2,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/e9/itt-12-91.PMC10546931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Immunotherapies for Myasthenia Gravis.","authors":"Sruthi S Nair, Saiju Jacob","doi":"10.2147/ITT.S377056","DOIUrl":"10.2147/ITT.S377056","url":null,"abstract":"<p><p>Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG and long-term toxicities of the medications have been major concerns with the conventional therapies. Advances in the immunology and pathogenesis of MG have ushered in an era of newer therapies which are more specific and efficacious. Complement inhibitors and neonatal Fc receptor blockers target disease-specific pathogenic mechanisms linked to myasthenia and have proven their efficacy in pivotal clinical studies. B cell-depleting agents, specifically rituximab, have also emerged as useful for the treatment of severe MG. Many more biologicals are in the pipeline and in diverse stages of development. This review discusses the evidence for the novel therapies and the specific issues related to their clinical use.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"25-45"},"PeriodicalIF":6.2,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/44/itt-12-25.PMC10082579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10661803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Nomogram for Hyperprogressive Disease During Anti-PD-1/PD-L1 Treatment in Patients with Advanced Non-Small Cell Lung Cancer.","authors":"Xueping Wang,&nbsp;Zhixing Guo,&nbsp;Xingping Wu,&nbsp;Da Chen,&nbsp;Fang Wang,&nbsp;Lewei Yang,&nbsp;Min Luo,&nbsp;Shaocong Wu,&nbsp;Chuan Yang,&nbsp;Lamei Huang,&nbsp;Liwu Fu","doi":"10.2147/ITT.S373866","DOIUrl":"https://doi.org/10.2147/ITT.S373866","url":null,"abstract":"<p><strong>Introduction: </strong>Various studies have reported that anti-PD-1/PD-L1 treatment may lead to the rapid development of tumors called hyperprogressive disease (HPD). A nomogram for HPD prediction in NSCLC patients is urgently needed.</p><p><strong>Methods: </strong>This retrospective cohort study included 176 cases for establishing a model of HPD prediction and 85 cases for validation in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. HPD was defined as tumor growth rate (TGR, ≥ 2), tumor growth kinetics (TGK, ≥ 2) or time to treatment failure (TTF, ≤ 2 months). Univariate and multivariate logistic regression were used to estimate the specified factors associated with HPD. Then, the nomogram was developed and validated.</p><p><strong>Results: </strong>Anti-PD-1/PD-L1 therapy resulted in a 9.66% (17/176) incidence of HPD in advanced NSCLC. The overall survival (OS) and progression-free survival (PFS) in patients with HPD were significantly shorter than those in patients without HPD (OS: 7.00 vs 12.00 months, P<0.01; PFS: 2.00 vs 5.00 months, P<0.001, respectively). The HPD prediction nomogram included APTT (P<0.01), CD4+ CD25+ CD127-low cells (Treg cells) (P<0.01), the presence of liver metastasis (P<0.05), and more than two metastatic sites (P<0.05). Then, patients were divided into two groups by the \"HPD score\" calculated by the nomogram. The C-index was 0.845, while the area under the curve (AUC) was 0.830 (sensitivity 75.00%, specificity 91.70%). The calibration plot of HPD probability showed an optimal agreement between the actual observation and prediction by the nomogram. In the validation cohort, the AUC was up to 0.960 (sensitivity 88.70%, specificity 89.80%).</p><p><strong>Conclusions: </strong>The nomogram was constructed with the presence of liver metastasis, more than two metastatic sites, lengthened APTT and a high level of Treg cells, which could be used to predict HPD risk.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"1-16"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/9d/itt-12-1.PMC9828302.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab Treatment is Not Associated with Increased Risk of Overall Skin Infections [Letter].","authors":"Simmi Wiggins,&nbsp;Noah A Levit","doi":"10.2147/ITT.S421440","DOIUrl":"https://doi.org/10.2147/ITT.S421440","url":null,"abstract":"Dear editor The article by Labib et al provides a valuable review of prurigo nodularis (PN). Dupilumab, recently approved by the U. S. Food and Drug Administration as the only systemic therapy for the treatment of PN, is mentioned among novel immunotherapies under investigation. Dupilumab safety is reviewed based on clinical trial data for atopic dermatitis (AD). However, the article cites skin infections as adverse reactions more commonly associated with dupilumab relative to placebo, a point that we believe warrants clarification. Eichenfield et al analyzed pooled data from 7 randomized, placebo-controlled trials in adults with AD and found that the exposure-adjusted proportion of patients with treatment-emergent non-herpetic adjudicated skin infections was significantly lower with dupilumab than with placebo (14.5% vs 26.6%, p &lt; 0.001). In the same study, the incidence of herpetic infections was non-significantly higher with dupilumab (12.7% vs 10.4%, p = 0.24), while eczema herpeticum and herpes zoster were significantly less frequent with dupilumab versus placebo (1.1% vs 3.6%, p = 0.004). Similarly, in a pooled analysis of 2 randomized, placebo-controlled trials in children aged 6–17 years with AD, Paller et al reported significantly lower exposure-adjusted proportions of patients with total and nonherpetic skin infections in the dupilumab group versus placebo (respectively, 35.9% vs 67.0%, p = 0.001 and 27.8% vs 56.9%, p = 0.004), while herpes viral infections did not differ significantly (total herpes infections, 8.9% vs 14.7%, p = 0.262; eczema herpeticum, 0.8% vs 1.6%, p = 0.628; herpes zoster, 0.8% vs 0, p = 1.0). Additionally, Blauvelt et al analyzed treatment-emergent infections over 4 years of dupilumab treatment in an AD open-label study and found that the cumulative number of patients with serious or severe infections, non-herpetic or herpetic infections, and total skin infections, decreased yearly with continued treatment. In PN, subsequent to the publication of Labib et al, results from Phase 3 randomized LIBERTY-PN PRIME and PRIME2 trials showed, similarly to AD trials, that non-herpetic skin infections occurred less frequently in patients treated with dupilumab versus placebo (2.7% vs 9.3% in PRIME, and 5.2% vs 6.1% in PRIME2); herpetic skin infections did not occur in PRIME and were more frequent with dupilumab in PRIME2 (5.2% vs 0). AD patients are highly susceptible to non-herpetic skin infections, usually with Gram-positive bacteria, and dupilumab was shown to decrease abundance of Staphylococcus aureus in both AD lesional and non-lesional skin, results further supported by comprehensive evidence from clinical trials and post-marketing studies. Herpes infections are a known adverse drug reaction in both AD and PN and included in the U.S. prescribing information. In conclusion, evidence from AD and PN trials demonstrates that dupilumab treatment does not increase the risk of skin infections overall, and is associated with f","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"77-78"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/18/itt-12-77.PMC10226537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards Early Diagnosis of Mixed Connective Tissue Disease: Updated Perspectives.","authors":"Chiara Alfia Ferrara,&nbsp;Gaetano La Rocca,&nbsp;Giuseppe Ielo,&nbsp;Alessandro Libra,&nbsp;Gianluca Sambataro","doi":"10.2147/ITT.S390023","DOIUrl":"https://doi.org/10.2147/ITT.S390023","url":null,"abstract":"<p><p>Mixed Connective Tissue Disease (MCTD) is an autoimmune disease first described by Sharp et al in 1972, characterized by the presence of anti-Ribonucleoprotein antibodies directed against the U1 complex (anti-U1RNP). The condition shares clinical characteristics with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis. Diagnosis is quite difficult due to its rarity, the lack of validated classification criteria, and its heterogeneous clinical presentation. While in the early stages its nuanced clinical features might lead to it being incorrectly classified as other Connective Tissue Diseases (CTDs) or even not recognized, in cases of longstanding disease its classification as a CTD is clear but challenging to discriminate from overlap syndromes. MCTD should be considered a distinct entity due to the presence of a specific genetic substrate and the presence of the high titer of a specific autoantibody, anti-U1RNP, present in all the commercial kits for Extractable Nuclear Antigens, and almost always associated with Antinuclear Antibody positivity with a coarse speckled pattern. Except for anti-U1RNP, no specific biomarkers are available to guide clinicians to a correct classification of MCTD, which is arrived at by the association of clinical, serological and instrumental evaluation. In the first stages, the disease is mainly characterized by Raynaud's phenomenon, inflammatory arthritis, puffy fingers, myalgia and/or myositis, and rarely, trigeminal neuropathy. Longstanding disease is generally associated with the development of Pulmonary Hypertension and Interstitial Lung Disease, which are the two main causes of mortality in MCTD. The aim of this review is to summarize current knowledge on the early recognition of MCTD.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"79-89"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/39/itt-12-79.PMC10387239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Complete Remission in Proficient Mismatch Repair (pMMR) Advanced Colon Cancer Treated with Sintilimab and XELOX.","authors":"Jiangpeng Zhu,&nbsp;Guangyao Li,&nbsp;Zhengjun Zhang,&nbsp;Yandong Wang","doi":"10.2147/ITT.S393526","DOIUrl":"https://doi.org/10.2147/ITT.S393526","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is the 3rd most common malignant tumors after breast cancer and lung cancer, accounting for 9.4% of patients. Some patients had distant metastasis at the time of diagnosis without surgery opportunity. It is particularly important to prolong patient survival and improve quality of life.</p><p><strong>Patient concerns: </strong>A 73-year-old female was admitted with discomfort over 2 months. Enlarged lymph nodes in the left supraclavicular fossa were observed in chest computed tomography (CT). Enhanced abdominal CT showed thickening of the right colon wall with multiple metastatic lymph nodes in the abdomen. Colonoscopy showed ileocecal mass and pathology showed moderately and poorly differentiated adenocarcinoma. Physical examination showed a 2*2 cm lymph node could be touched in the left supraclavicular fossa. The patient was diagnosed advanced colon cancer by the histopathological examination and imaging findings. Actually, it is hardly to resect radically.</p><p><strong>Intervention: </strong>Sintilimab combined with XELOX was initiated. Two period of treatment after initial therapy, laparoscopic radical resection of right colon cancer was performed successfully.</p><p><strong>Outcomes: </strong>After conversion treatment, the enlarged lymph nodes and primary tumor were significantly reduced. The patient was discharged successfully three weeks after surgery. Both specimen and 14 lymph nodes dissected showed no malignancy in pathology. Tumor regression grading (TRG) is 0, which indicate complete regression with no residual tumor cells including lymph nodes. The patient obtained a pathological complete response (pCR).</p><p><strong>Lessons: </strong>The patient achieved a great therapeutic benefit with the above-mentioned chemotherapy in this case. The case provides a potential reference for pMMR CRC patients treating with immune checkpoint inhibitors (ICIs).</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"17-23"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/bd/itt-12-17.PMC9951411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10792393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Toll-like Receptors 1, 2, 4, 6, 8, 9 and 10 Genes Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Sudanese Patients.","authors":"Najwa A Mhmoud","doi":"10.2147/ITT.S404915","DOIUrl":"https://doi.org/10.2147/ITT.S404915","url":null,"abstract":"<p><strong>Background: </strong>Genetic factors are important contributors to the development of a wide range of complex disease. Polymorphisms in genes encoding for toll-like receptors (TLRs) usually influence the efficiency of the immune response to infection and are associated with disease susceptibility and progression. Therefore, we aim to describe the first association between TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Sudanese patients.</p><p><strong>Methodology: </strong>Here we performed a case study which included 160 tuberculosis patients and 220 healthy matched controls from Sudan. In the study population, we evaluated the possible association between 86 markers in TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to PTB disease in Sudanese population using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).</p><p><strong>Results: </strong>From our results it appeared that in the PTB population the TLR1 (rs5743557, rs4833095, rs5743596), TLR2 (rs5743704, rs5743708, rs3804099), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810), TLR8 (rs3764879, rs3764880), TLR9 (rs352165, rs352167, rs187084) and TLR10 (rs4129009) were significantly more often encountered (p<0.0001) than in the control population and were associated with PTB in the Sudanese population. For the other polymorphisms tested, no association with PTB was found in the population tested.</p><p><strong>Conclusion: </strong>The work describes novel mutations in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9 and TLR10 genes and their association with PTB infection in Sudanese population. These results will enhance our ability to determine the risk of developing the disease by targeting specific TLR pathways to reduce the severity of the disease. Future studies are needed in a larger sample to replicate our findings and understand the mechanism of association of TLR polymorphism in PTB.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"47-75"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/0a/itt-12-47.PMC10085002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9304349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}