ProCite
RefWorks
Reference Manager
BibTeX
Zotero
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-
1.
Polycarpou A, Walker SL, Lockwood DN, 2017. A systematic review of immunological studies of erythema nodosum leprosum. Front Immunol 8: 233.
-
2.
Walker SL, Lockwood DN, 2008. Leprosy type 1. (Reversal) reactions and their management. Lepr Rev 79: 372–386.
-
3.
Nery JA, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira Sde S, Sales AM, 2013. Understanding the type 1 reactional state for early diagnosis and treatment: A way to avoid disability in leprosy. An Bras Dermatol 88: 787–792.
-
4.
Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, 2023. National Leprosy Eradication Programme. Available at: https://dghs.gov.in/content/1349_3_NationalLeprosyEradicationProgramme.aspx. Accessed May 12, 2023.
-
5.
Sardana K, Khurana A, 2020. Immunopathogenesis of reactions. Sardana K & Khurana A Jopling’s Handbook of Leprosy. 6th ed. New Delhi, India: CBS, 182–187.
-
6.
Khurana A, 2023. Bacteriology of leprosy. Sardana K & Khurana A Jopling’s Handbook of Leprosy. 7th ed. New Delhi, India: CBS, 160–167.
-
7.
Saini C, Siddiqui A, Ramesh V, Nath I, 2016. Leprosy reactions show increased Th17 cell activity and reduced FOXP3+ Tregs with concomitant decrease in TGF-beta and increase in IL-6. PLoS Negl Trop Dis 10: e0004592.
-
8.
Vieira AP, Trindade MA, Pagliari C, Avancini J, Sakai-Valente NY, Duarte AJ, Bernard G, 2016. Development of type 2, but not type 1, leprosy reactions is associated with a severe reduction of circulating and in situ regulatory T-cells. Am J Trop Med Hyg 94: 721–727.
-
9.
Costa MB, Hungria EM, Freitas AA, Sousa ALOM, Jampietro J, Soares FA, Stefani MMA, 2018. In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions. PLoS One 13: e0196853.
-
10.
Saini C, Srivastava RK, Tarique M, Kurra S, Khanna N, Ramesh V, Sharma A, 2020. Elevated IL 6R on CD4+ T cells promotes IL 6 driven Th17 cell responses in patients with T1R leprosy reactions. Sci Rep 10: 15143.
-
11.
World Health Organization, 2018. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. Available at: https://www.who.int/publications/i/item/9789290226383. Accessed May 18, 2023.
-
12.
Walker SL, Nicholls PG, Butlin CR, Nery JA, Roy HK, Rangel E, Sales AM, Lockwood DN, 2008. Development and validation of a severity scale for leprosy type 1 reactions. PLoS Negl Trop Dis 2: e351.
-
13.
Pfaffl MW, 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.
-
14.
Saini C, Ramesh V, Nath I, 2013. CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, non Th2 T cells in human leprosy. PLoS Negl Trop Dis 7: e2338.
-
15.
Saini C, Ramesh V, Nath I, 2014. Increase in TGF-β secreting CD4+ CD25+ FOXP3+ T regulatory cells in anergic lepromatous leprosy patients. PLoS Negl Trop Dis 8: e2639.
-
16.
Kumar S, Naqvi RA, Ali R, Rani R, Khanna N, Rao DN, 2013. CD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy. Mol Immunol 56: 513–520.
-
17.
Tarique M, Saini C, Naqvi RA, Khanna N, Rao DN, 2017. Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients. Cytokine 91: 82–88.
-
18.
Andersson AK, Chaduvula MV, Atkinson SE, Khanolkar-Young S, Jain S, Suneetha L, Lockwood DN, 2005. Effects of prednisolone treatment on cytokine expression in patients with leprosy type 1 reactions. Infect Immun 73: 3725–3733.
-
19.
Chaitanya S, Lavania M, Turankar RP, Karri SR, Sengupta U, 2012. Increased serum circulatory levels of interleukin 17F in type 1 reactions of leprosy. J Clin Immunol 32: 1415–1420.
-
20.
Abdallah M, Attia EAS, Saad AA, El-Khateeb EA, Lotfi RA, Abdallah M, El-Shennawy D, 2014. Serum Th1/Th2 and macrophage lineage cytokines in leprosy; Correlation with circulating CD4+ CD25high FoxP3+ T-regs cells. Exp Dermatol 23: 742–747.
-
21.
Parente JN, Talhari C, Schettini AP, Massone C, 2015. T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states. An Bras Dermatol 90: 41–47.
-
22.
Azevedo MCS, et al., 2017. Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct 141 patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events. Med Microbiol Immunol (Berl) 206: 429–439.
-
23.
Santos MB, et al., 2017. Distinct roles of Th17 and Th1 cells in inflammatory responses associated with the presentation of paucibacillary leprosy and leprosy reactions. Scand J Immunol 86: 40–49.
-
24.
Zhou L, et al., 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453: 236–240.
-
25.
Atkinson SE, Khanolkar-Young S, Marlowe S, Jain S, Reddy RG, Suneetha S, Lockwood DN, 2004. Detection of IL-13, IL-10, and IL-6 in the leprosy skin lesions of patients during prednisolone treatment for type 1 (T1R) reactions. Int J Lepr Other Mycobact Dis 72: 27–34.
-
26.
Manandhar R, Shrestha N, Butlin CR, Roche PW, 2002. High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy. Clin Exp Immunol 128: 333–338.
-
27.
Little D, Khanolkar-Young S, Coulthart A, Suneetha S, Lockwood DN, 2001. Immunohistochemical analysis of cellular infiltrate and gamma interferon, interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1 (reversal) reactions before and during prednisolone treatment. Infect Immun 69: 3413–3417.
-
28.
Faber WR, Iyer AM, Fajardo TT, Dekker T, Villahermosa LG, Abalos RM, Das PK, 2004. Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Lepr Rev 75: 274–281.
-
29.
Moraes MO, Sarno EN, Teles RM, Almeida AS, Saraiva BC, Nery JA, Sampaio EP, 2000. Antiinflammatory drugs block cytokine mRNA accumulation in the skin and improve the clinical condition of reactional leprosy patients. J Invest Dermatol 115: 935–941.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 463 | 463 | 89 |
| Full Text Views | 6 | 6 | 4 |
| PDF Downloads | 6 | 6 | 4 |
Th17 and T Regulatory Cytokines in Serum, Lesional Skin, and Stimulated Peripheral Blood Mononuclear Cell Culture Supernatants from Type 1 Leprosy Reaction Patients
Srishti Dabas
Srishti Dabas
Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India;
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Ananta Khurana
drananta2014@gmail.com
Ananta Khurana
Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India;
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Itu Singh
Itu Singh
Stanley Browne Laboratory, The Leprosy Mission Community Hospital, New Delhi, India;
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Vinay Kumar Pathak
Vinay Kumar Pathak
Stanley Browne Laboratory, The Leprosy Mission Community Hospital, New Delhi, India;
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Parul Goyal
Parul Goyal
Department of Biochemistry, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India;
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Kabir Sardana
Kabir Sardana
Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India;
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Sanjeet Panesar
Sanjeet Panesar
Department of Community Medicine, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India
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Savitha Sharath
Savitha Sharath
Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India;
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ABSTRACT.
There are conflicting reports regarding the roles of T helper-17 (Th17) and T regulatory (Treg) cells in type 1 leprosy reactions (T1Rs). Also, literature on the correlation of immunological parameters with a validated scoring system and the effect of treatment on cytokines is lacking. Adult patients with untreated T1R and nonreactional spectrum–matched controls were included in the study for comparison of levels of Th17 and Treg pathway cytokines in serum, skin lesions (reactional), and peripheral blood mononuclear cells (PBMCs) culture supernatants. Venous blood samples were collected at baseline and after resolution of reaction (post treatment with nonsteroidal anti-inflammatory drugs [NSAIDs] or steroids) for serum cytokine estimation and PBMC stimulation assays, and lesional (reactional) skin biopsy for cytokine messenger RNA (mRNA) estimation. Thirty-two cases of T1R were recruited (23 patients completed follow-up). Serum levels of cytokines were not significantly different between cases and controls or between pre- and post-treatment samples. Tissue mRNA and Mycobacterium leprae (M. leprae) antigen–stimulated PBMC culture supernatant levels of Interleukin (IL)-17A, IL-17F, IL-6, and IL-23 were significantly higher in T1R than in controls. Levels of IL-10 and Transforming Growth Factor-beta (TGF-β) were comparable among the two groups. The levels of all cytokines were significantly reduced after treatment. There was no significant difference in magnitude of the fall between those treated with steroids versus NSAIDs. This study suggests heightened Th17 response in T1R, with a prominent inability of the regulatory cytokines IL-10 and TGF-β to control the associated inflammation. The dynamics of change after resolution of T1R were comparable between NSAID and oral steroid treatment groups.
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Author Notes
Current contact information: Srishti Dabas, Ananta Khurana, Kabir Sardana, and Savitha Sharath, Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India, E-mails: ssdabass@gmail.com, drananta2014@gmail.com, kabirijdvl@gmail.com, and savitharavivarma@gmail.com. Itu Singh and Vinay Kumar Pathak, The Leprosy Mission Community Hospital, New Delhi, India, E-mails: itusingh@gmail.com and pathakv.vp@gmail.com. Parul Goyal, Department of Biochemistry, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi, India, E-mail: drparulgoyal@yahoo.com. Sanjeet Panesar, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram, Manohar Lohia Hospital, New Delhi, India, E-mail: panesarsanjeet@gmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Polycarpou A, Walker SL, Lockwood DN, 2017. A systematic review of immunological studies of erythema nodosum leprosum. Front Immunol 8: 233.
-
2.
Walker SL, Lockwood DN, 2008. Leprosy type 1. (Reversal) reactions and their management. Lepr Rev 79: 372–386.
-
3.
Nery JA, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira Sde S, Sales AM, 2013. Understanding the type 1 reactional state for early diagnosis and treatment: A way to avoid disability in leprosy. An Bras Dermatol 88: 787–792.
-
4.
Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, 2023. National Leprosy Eradication Programme. Available at: https://dghs.gov.in/content/1349_3_NationalLeprosyEradicationProgramme.aspx. Accessed May 12, 2023.
-
5.
Sardana K, Khurana A, 2020. Immunopathogenesis of reactions. Sardana K & Khurana A Jopling’s Handbook of Leprosy. 6th ed. New Delhi, India: CBS, 182–187.
-
6.
Khurana A, 2023. Bacteriology of leprosy. Sardana K & Khurana A Jopling’s Handbook of Leprosy. 7th ed. New Delhi, India: CBS, 160–167.
-
7.
Saini C, Siddiqui A, Ramesh V, Nath I, 2016. Leprosy reactions show increased Th17 cell activity and reduced FOXP3+ Tregs with concomitant decrease in TGF-beta and increase in IL-6. PLoS Negl Trop Dis 10: e0004592.
-
8.
Vieira AP, Trindade MA, Pagliari C, Avancini J, Sakai-Valente NY, Duarte AJ, Bernard G, 2016. Development of type 2, but not type 1, leprosy reactions is associated with a severe reduction of circulating and in situ regulatory T-cells. Am J Trop Med Hyg 94: 721–727.
-
9.
Costa MB, Hungria EM, Freitas AA, Sousa ALOM, Jampietro J, Soares FA, Stefani MMA, 2018. In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions. PLoS One 13: e0196853.
-
10.
Saini C, Srivastava RK, Tarique M, Kurra S, Khanna N, Ramesh V, Sharma A, 2020. Elevated IL 6R on CD4+ T cells promotes IL 6 driven Th17 cell responses in patients with T1R leprosy reactions. Sci Rep 10: 15143.
-
11.
World Health Organization, 2018. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. Available at: https://www.who.int/publications/i/item/9789290226383. Accessed May 18, 2023.
-
12.
Walker SL, Nicholls PG, Butlin CR, Nery JA, Roy HK, Rangel E, Sales AM, Lockwood DN, 2008. Development and validation of a severity scale for leprosy type 1 reactions. PLoS Negl Trop Dis 2: e351.
-
13.
Pfaffl MW, 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.
-
14.
Saini C, Ramesh V, Nath I, 2013. CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, non Th2 T cells in human leprosy. PLoS Negl Trop Dis 7: e2338.
-
15.
Saini C, Ramesh V, Nath I, 2014. Increase in TGF-β secreting CD4+ CD25+ FOXP3+ T regulatory cells in anergic lepromatous leprosy patients. PLoS Negl Trop Dis 8: e2639.
-
16.
Kumar S, Naqvi RA, Ali R, Rani R, Khanna N, Rao DN, 2013. CD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy. Mol Immunol 56: 513–520.
-
17.
Tarique M, Saini C, Naqvi RA, Khanna N, Rao DN, 2017. Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients. Cytokine 91: 82–88.
-
18.
Andersson AK, Chaduvula MV, Atkinson SE, Khanolkar-Young S, Jain S, Suneetha L, Lockwood DN, 2005. Effects of prednisolone treatment on cytokine expression in patients with leprosy type 1 reactions. Infect Immun 73: 3725–3733.
-
19.
Chaitanya S, Lavania M, Turankar RP, Karri SR, Sengupta U, 2012. Increased serum circulatory levels of interleukin 17F in type 1 reactions of leprosy. J Clin Immunol 32: 1415–1420.
-
20.
Abdallah M, Attia EAS, Saad AA, El-Khateeb EA, Lotfi RA, Abdallah M, El-Shennawy D, 2014. Serum Th1/Th2 and macrophage lineage cytokines in leprosy; Correlation with circulating CD4+ CD25high FoxP3+ T-regs cells. Exp Dermatol 23: 742–747.
-
21.
Parente JN, Talhari C, Schettini AP, Massone C, 2015. T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states. An Bras Dermatol 90: 41–47.
-
22.
Azevedo MCS, et al., 2017. Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct 141 patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events. Med Microbiol Immunol (Berl) 206: 429–439.
-
23.
Santos MB, et al., 2017. Distinct roles of Th17 and Th1 cells in inflammatory responses associated with the presentation of paucibacillary leprosy and leprosy reactions. Scand J Immunol 86: 40–49.
-
24.
Zhou L, et al., 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453: 236–240.
-
25.
Atkinson SE, Khanolkar-Young S, Marlowe S, Jain S, Reddy RG, Suneetha S, Lockwood DN, 2004. Detection of IL-13, IL-10, and IL-6 in the leprosy skin lesions of patients during prednisolone treatment for type 1 (T1R) reactions. Int J Lepr Other Mycobact Dis 72: 27–34.
-
26.
Manandhar R, Shrestha N, Butlin CR, Roche PW, 2002. High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy. Clin Exp Immunol 128: 333–338.
-
27.
Little D, Khanolkar-Young S, Coulthart A, Suneetha S, Lockwood DN, 2001. Immunohistochemical analysis of cellular infiltrate and gamma interferon, interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1 (reversal) reactions before and during prednisolone treatment. Infect Immun 69: 3413–3417.
-
28.
Faber WR, Iyer AM, Fajardo TT, Dekker T, Villahermosa LG, Abalos RM, Das PK, 2004. Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Lepr Rev 75: 274–281.
-
29.
Moraes MO, Sarno EN, Teles RM, Almeida AS, Saraiva BC, Nery JA, Sampaio EP, 2000. Antiinflammatory drugs block cytokine mRNA accumulation in the skin and improve the clinical condition of reactional leprosy patients. J Invest Dermatol 115: 935–941.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 463 | 463 | 89 |
| Full Text Views | 6 | 6 | 4 |
| PDF Downloads | 6 | 6 | 4 |