Table 1. Summary of selected study characteristics.

No.	Title	Author (Country where the research was carried out, year)	Aim of Study	Population	Results and Conclusions
1.	Neutrophil extracellular traps contribute to the pathogenesis of leprosy type 2 reaction.	Da Silva et al. (Brazil, 2019) [8]	To examine the production of neutrophil extracellular traps (NETs) in patients with type 2 leprosy reaction.	Forty individuals diagnosed with leprosy were categorized into two groups based on their leprosy reactions.	Both the whole-cell sonicate of Mycobacterium leprae and the CpG-Hlp complex, acting as a surrogate for a mycobacterial Toll-like receptor 9 (TLR9) ligand, have the potential to trigger the formation of neutrophil extracellular traps. There is a possible involvement of neutrophil extracellular traps in the development of type 2 leprosy reaction.
2.	Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In Situ Regulatory T-Cells	Vieira et al. (Brazil, 2016) [9]	To investigate the underlying mechanisms responsible for the reduction of Tregs in patients with type 2 leprosy reaction conditions.	Twenty-eight individuals exhibit clinically active and severe reactions.	Patients with type 2 leprosy reactions demonstrate notably reduced circulating and in situ quantities. Tregs were compared to both type 1 leprosy reaction patients and the control group. The observed decline was accompanied by a concurrent rise in interleukin-17 (IL-17) expression within the local environment while transforming growth factor-beta (TGF-β) expression experienced a decline.
3.	Gene Set Signature of Reversal Reaction Type I in Leprosy Patients	Orlova et al. (Vietnam and Canada, 2013) [10]	To identify the type 1 leprosy reaction gene set and assess as well as validate the findings using a retrospective design.	A cohort of 43 persons was recently diagnosed with borderline leprosy without type 1 leprosy reaction.	The results suggest a role for intrinsic factors in type 1 leprosy reaction, which is a first step toward establishing a prognostic genetic profile for type 1 leprosy reaction.
4.	Downmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions	De Castro et al. (Brazil, 2022) [11]	To conduct a phenotypic and functional analysis of CD4+ and CD8+ Treg cells both in their ex vivo state and in response to Mycobacterium leprae.	Twenty-two people were divided into three groups. Eighteen newly diagnosed and untreated individuals Multibacillary. Nineteen individuals had undergone type 1 leprosy or type 2 leprosy reaction episodes of reactional Multibacillary, and 15 healthy volunteers served as controls.	A reduction in the populations of CD4+ transforming growth factor-beta (TGF-β+) Tregs and CD8+transforming growth factor-beta (TGF-β+) Tregs has been seen in persons affected with Multibacillary during both types of reactional episodes.  Alterations in the cytokine profile were additionally observed in type 2 leprosy reaction., concomitant with an elevation in the concentrations of interleukin-17 (IL-17) and interleukin-6 (IL-6) in the supernatant.
5.	Differential immunoglobulin and complement levels in leprosy prior to the development of reversal reaction and erythema nodosum leprosum	Amorim et al. (Brazil, 2019) [12]	This study looks into the biological variables influencing differences in gene expression within the canonical pathways connected to complement and immunoglobulin in the setting of immune responses to leprosy.	The population size is 96 with aged 18 years and above	The presence of reduced C4 levels and increased anti-Mycobacterium leprae antibodies among individuals newly diagnosed with leprosy may serve as risk factors for the eventual occurrence of leprosy immunological reactions.
6.	T-cell regulation in Erythema Nodosum Leprosum	Negera et al. (Ethiopia, 2017) [13]	To examine the Treg-cells in individuals diagnosed with erythema nodosum leprosum, a comprehensive investigation was conducted.	A cohort of 46 individuals exhibiting erythema nodosum leprosum reaction and 31 individuals with non-reactional Lepromatous-leprosy were selected.	There is a correlation between the presence of erythema nodosum leprosum and a reduction in the proportion of Treg-cells, as well as an increase in the CD4+ to CD8+ T-cell ratio. Additionally, there is an observed rise in the amount of interleukin-17 (IL-17)-producing T-cells. The initiation erythema nodosum leprosum reactions can be attributed to dysregulation of the immune system.
7.	Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions	Negera et al. (Ethiopia, 2017) [14]	To investigate the role of B-cells in the development of erythema nodosum leprosum, it is imperative to conduct a thorough analysis.	Patients diagnosed with erythema nodosum leprosum were administered a course of steroid treatment. Multi-drug therapy was administered to all individuals diagnosed with leprosy. The total number of patients was 60.	Patients who did not receive treatment for erythema nodosum leprosum exhibited a greater abundance of B-cells that had encountered antigens and were in an activated state, as compared to persons who did not have this reaction, specifically Lepromatous-leprosy patients. This observation implies a connection between B-cells and the pathogenesis of erythema nodosum leprosum.
8.	Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum	Schmitz et al. (Brazil, 2016) [15]	To examine the expression of CD64 during erythema nodosum leprosum and determine whether thalidomide medication had any effect on its expression.	In Group I, there were a total of 16 health volunteers, consisting of 7 females and nine males. Group II consisted of 62 individuals diagnosed with leprosy, comprising 46 males and 16 females. The total number of patients in the study was 78.	There was a positive correlation observed between the severity of erythema nodosum leprosum symptoms and the level of CD64 expression. The potential utility of CD64 expression in neutrophils as a predictive biomarker for erythema nodosum leprosum is noteworthy. Furthermore, assessing the CD64 response could offer valuable insights into the severity of this particular medical issue.
9.	Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with the Presentation of Paucibacillary Leprosy and Leprosy Reactions	Santos et al. (Brazil, 2017) [16]	To comprehensively examine the inflammatory cytokine profile linked to the various clinical manifestations of leprosy, a unified approach is employed.	A total of 74 patients were identified who had symptoms of leprosy, leprosy responses, and neurological impairments. Each individual possessed a scar that served as evidence of a previous Bacillus Calmette-Guérin (BCG) immunization.	T-helper-17 cells significantly facilitate a robust inflammatory response, ultimately developing paucibacillary forms in individuals affected with leprosy. Nevertheless, these cells do not function as a prognostic indicator for the eventual manifestation of inflammatory leprosy reactions in patients with multibacillary. This suggests that T-helper-17 cells provide immunity against Mycobacterium leprae infection and play a role in the progression of milder clinical symptoms in individuals with leprosy.