Department of Microbial Pathogenesis & Genomics Laboratory, Indian Council of Medical Research-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh, India.
Indian J Dermatol Venereol Leprol. 2024 Nov-Dec;90(6):731-741. doi: 10.25259/IJDVL_532_2022.
Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.
麻风病不再被视为诅咒，因为全球范围内都有有效的多药物治疗方案来治愈它。然而，其多样化的临床表现有时涉及急性炎症反应。这些并发症导致不可逆转的神经损伤、神经炎和解剖畸形，这些在治疗前、治疗期间或治疗后出现。逆转反应（I 型）和结节性红斑麻风（II 型）是麻风患者中常见的麻风反应，见于瘤型和边界型麻风。目前，尚无准确的诊断试验可用于检测这些麻风反应。目的：确定指示 I 型和 II 型麻风反应的潜在生物标志物，以帮助早期诊断。方法和结果：本研究利用宿主转录组学研究来破译基于宿主基因表达的生物标志物与麻风反应恶化之间的相关性。我们对与麻风反应相关的公共可用宿主转录组学数据集（来自基因表达综合数据库）进行了比较分析。对单个数据集进行了分析，并使用荟萃分析进行了结果整合。使用频率主义和贝叶斯比值关联测试方法鉴定共同差异表达基因（DEG）。我们已经确定了几个基因 - ADAMTS5、ADAMTS9、IFITM2、IFITM3、KIRREL、ANK3、CD1E、CTSF、DOCK9 和 KRT73 等 - 它们可以作为 II 型反应的潜在生物标志物。同样，ACP5、APOC1、CCL17、S100B、SLC11A1 等可能作为 I 型反应的生物标志物。局限性：系统性搜索后发现与麻风反应相关的数据集数量较少（n = 4），这可能限制了鉴定生物标志物基因的准确性。通过在数据分析中纳入更多研究，可以解决这个问题。结论：我们提供了一个全面的基因候选列表，这些基因在聚焦于麻风病免疫反应的研究中可以进一步优先考虑，因为它们在理解其复杂性方面可能很重要，并可能有助于其早期诊断。
