Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients

Ferreira, Helen; Mendes, Mayara Abud; Barbosa, Mayara Garcia de Mattos; Oliveira, E. B. de; Sales, Anna Maria; Moraes, Milton Ozório; Sarno, Euzenir Nunes; Pinheiro, Roberta Olmo

doi:10.3389/fimmu.2021.662307

Cited by 5 publications

(17 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upregulation of CD8 antigen in reversal reactions has also been noted in leprosy/HIV co-infections (de Oliveira et al, 2013). Several studies revealed the upregulation of CXCL10 (IP10) in reactional states of leprosy (Chaitanya al., 2013;van Hooij et al, 2016;Ferreira et al, 2021). Expression of IP-10 is seen in many Th1-type inflammatory diseases, where it is thought to play an important role in recruiting activated T cells into sites of tissue inflammation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy

et al. 2023

View full text Add to dashboard Cite

BackgroundMycobacterium leprae transcriptomic and human host immune gene expression signatures that demonstrate a plausible association with type I (T1R) and type II reactions (T2R) aid in early diagnosis, prevention of nerve damage and consequent demyelinating neuropathy in leprosy. The aim of the study is to identify M. leprae and host-associated gene-expression signatures that are associated with reactional states in leprosy.MethodsThe differentially expressed genes from the whole transcriptome of M. leprae were determined using genome-wide hybridization arrays with RNA extracted from skin biopsies of 20 T1R, 20 T2R and 20 non reactional controls (NR). Additionally, human immune gene-expressions were profiled using RT2-PCR profiler arrays and real-time qPCRs.ResultsThe RNA quality was optimal in 16 NR, 18 T1R and 19 T2R samples. Whole transcriptome expression array of these samples revealed significant upregulation of the genes that encode integral and intrinsic membrane proteins, hydrolases and oxidoreductases. In T1R lesional skin biopsy specimens, the top 10 significantly upregulated genes are ML2064, ML1271, ML1960, ML1220, ML2498, ML1996, ML2388, ML0429, ML2030 and ML0224 in comparison to NR. In T2R, genes ML2498, ML1526, ML0394, ML1960, ML2388, ML0429, ML0281, ML1847, ML1618 and ML1271 were significantly upregulated. We noted ML2664 was significantly upregulated in T1R and repressed in T2R. Conversely, we have not noted any genes upregulated in T2R and repressed in T1R. In both T1R and T2R, ML2388 was significantly upregulated. This gene encodes a probable membrane protein and epitope prediction using Bepipred-2.0 revealed a distinct B-cell epitope. Overexpression of ML2388 was noted consistently across the reaction samples. From the host immune gene expression profiles, genes for CXCL9, CXCL10, CXCL2, CD40LG, IL17A and CXCL11 were upregulated in T1R when compared to the NR. In T2R, CXCL10, CXCL11, CXCL9, CXCL2 and CD40LG were upregulated when compared to the NR group.ConclusionA gene set signature involving bacterial genes ML2388, ML2664, and host immune genes CXCL10 and IL-17A can be transcriptomic markers for reactional states in leprosy.

show abstract

Section: Discussionmentioning

confidence: 99%

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Although, patients with psoriasis, rheumatoid arthritis with interstitial lung disease, viral meningitis, and other mycobacterial diseases like tuberculosis and sarcoidosis also have been discovered to express CXCL10. This suggest that CXCL10 is elevated in chronic inflammatory disease ( Makarem et al, 2024 ; Ferreira et al, 2021 ; Hungria et al, 2017 ).…”

Section: Introductionmentioning

confidence: 93%

“…Both TNF-α and IFN-γ have been found to attach to the macrophage cellular receptors in leprosy, resulting in creation of NO and free radicals that kill M. leprae ( de Sousa, Sotto & Quaresma, 2017 ). When pro-inflammatory conditions exist, a variety of cell types including leukocytes, monocytes, fibroblasts, activated neutrophils, epithelial cells, endothelial cells, mesenchymal cells, stromal cells, and keratinocytes release C-X-C motif chemokine ligand 10 or CXCL10, also known as interferon gamma induced protein (IP-10), in response to IFN-γ ( Makarem et al, 2024 ; Ferreira et al, 2021 ). However, an increase in CXCL10 is not always followed by an increase in IFN-γ.…”

Section: Introductionmentioning

confidence: 99%

“…Along with NF-κB, which controls the expression of genes critical for both innate and adaptive immune responses, TNF-α may also play a role in the induction of CXCL10 ( Hadi et al, 2021 ; Jin et al, 2017 ). It causes tissue injury by attracting macrophages, dendritic cells, natural killer (NK) cells, and activated T lymphocyte cells to inflammatory areas ( Ferreira et al, 2021 ; Pujiastuti, Agusni & Rahmadewi, 2017 ). CXCL10 can recruit effector Th1 cells to the site of delayed type hypersensitivity and previously has been identified in tuberculoid lesions of leprosy patients ( Stefani et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of CXCL10 as a biomarker for immunological response among patients with leprosy: a systematic literature review

Prakoeswa,

Haningtyas,

Dewi

et al. 2024

PeerJ

View full text Add to dashboard Cite

Introduction Involvement of a chemokine known as C-X-C motif chemokine ligand 10 or CXCL10 in the immunopathology of leprosy has emerged as a possible immunological marker for leprosy diagnosis and needed to be investigate further. The purpose of this systematic review is to assess CXCL10’s potential utility as a leprosy diagnostic tool and evaluation of therapy. Methods This systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. A thorough search was carried out to find relevant studies only in English and limited in humans published up until September 2023 using PubMed, Scopus, Science Direct, and Wiley Online Library database with keywords based on medical subject headings (MeSH) and no exclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized for quality assessment, while the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was utilized for assessing the risk of bias. Additionally, a narrative synthesis was conducted to provide a comprehensive review of the results. Results We collected a total of 115 studies using defined keywords and 82 studies were eliminated after titles and abstracts were screened. We assessed the eligibility of the remaining 26 reports in full text and excluded four studies due to inappropriate study design and two studies with incomplete outcome data. There were twenty included studies in total with total of 2.525 samples. The included studies received NOS quality evaluation scores ranging from 6 to 8. The majority of items in the risk bias assessment, using RoBANS, across all included studies yielded low scores. However, certain items related to the selection of participants and confounding variables showed variations. Most of studies indicate that CXCL10 may be a helpful immunological marker for leprosy diagnosis, particularly in leprosy reactions as stated in seven studies. The results are better when paired with other immunological markers. Its effectiveness in field-friendly diagnostic tools makes it one of the potential biomarkers used in diagnosing leprosy patients. Additionally, CXCL10 may be utilized to assess the efficacy of multidrug therapy (MDT) in leprosy patients as stated in three studies. Conclusion The results presented in this systematic review supports the importance of CXCL10 in leprosy diagnosis, particularly in leprosy responses and in tracking the efficacy of MDT therapy. Using CXCL10 in clinical settings might help with leprosy early diagnosis. Yet the findings are heterogenous, thus more investigation is required to determine the roles of CXCL10 in leprosy while taking into account for additional confounding variables.

show abstract

“…Our previous study demonstrated that PBMC from MB MDT-responders (MDT-R, with reduction of at least one log in BI after MDT) produced higher levels of CXCL10 in response to M. leprae when compared to cells from MDT-non-responders (MDT-NR, reduction lower than 1 log in BI after 12-doses MDT) MB patients (Ferreira et al, 2021). Here, we used host transcriptomic profiling by RNA-seq to explore differences in genes and pathways associated with a better response to treatment that could help suggest adjuvant or new and more effective antileprosy drugs.…”

Section: Introductionmentioning

confidence: 99%

Gene expression patterns associated with multidrug therapy in multibacillary leprosy

Ferreira

Leal-Calvo²,

Mendes³

et al. 2022

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

show abstract

Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients

Cited by 5 publications

References 60 publications

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy

The role of CXCL10 as a biomarker for immunological response among patients with leprosy: a systematic literature review

Gene expression patterns associated with multidrug therapy in multibacillary leprosy

Contact Info

Product

Resources

About