PD-1 and NFATc1 as promising immunotherapy for SLE patients
Main Article Content
Keywords
Systemic lupus erythematosus, NFATc1, PD-1
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with a wide range of clinical symptoms. This study aims to investigate PD-1 and NFATc1 gene expression in SLE patients.
Methodology: In this study, 50 diagnosed SLE patients (25 females as early diagnosed SLE without treatment, 25 females as SLE patients under treatment with (prednisolone, hydroxychloroquine) and 25 healthy individuals as control whose ages arranges from 20 to 45 years were included. The gene expression level of PD-1 and NFATc1 were assessed by real-time polymerase chain reaction (RT-PCR).
Results: A PD-1 gene expression level (folds) results showed a significant increase in the treated group (59.74 ± 33.26 folds) compared to early diagnosed group (23.18 ± 10.17 folds) and control group (3.46 ± 1.93 folds), and early diagnosed group showed a non-significant increase compared to control group. The NFATc1 gene expression level (folds) results showed a significant increase in the treated group (0.17 ± 0.16 folds) compared to early diagnosed group (0.003 ± 0.002 folds) and control group (0.001 ± 0.0007 folds), and early diagnosed group showed a non-significant increase compared to control group.
Conclusions: Based on these results, PD-1 and NFATc1 is important in the SLE pathogenesis. These results may hold promise for developing a new SLE immunotherapy by focusing on PD-1 and NFATc1.
References
1.Kamil MA, Kadr ZHM, Alabassi HM. Role of CXCL9-CXCR3 AXIS, ANA & DS-DNA ABS in Pathogenicity of SLE in Iraqi Patients. Pak J Med Health Sci 2022; 16: 398-398.
2. Shedid NH., Hafez EA., Akram SA, et al. Ultrasonographic abnormalities of wrist and metacarpophalangeal joints in a cohort of Egyptian patients with systemic lupus erythematosus. Egypt. J. Intern. Med. 2019; 31:951-957
3. Abdul-Majeed NG. Antibodies to selected minor target anti-neutrophil cytoplasmic antigens in systemic lupus patients. J Fac Med Baghdad 2015; 57:231-235.
4. Lisnevskaia L, Murphy G, Isenberg d. Systemic lupus erythematosus. Lancet 2014;384:1878-88.
5. Abbas AH, Melconian AK, Ad’hiah AH. Role of Helicobacter pylori infection in etiology of systemic lupus erythematosus. Curr Res Microbiol Biotechnol 2017; 5:1285-1288.
6. Abdualkader SN, Al-Shaikly AW, Al-Mousawy KM, et al. Correlation between Interleukin-4 and Interleukin-6 and auto antibodies in Systemic Lupus Erythematosus. J Fac Med Baghdad 2009;51:416-418.
7. Abdulridha RH, Saud AM, Alosami MH. Evaluation of Interferon Alpha (IFN-α) in Women with Systemic Lupus Erythematosus in Iraq. Iraqi J Sci 2022; 63:4225-4233.
8. Al-Hammamy HR, Abd KH, Khalil IA, Mahdi BM. Human Leukocyte Antigens Assosiation with Systemic Lupus Arythematosus In Iraqi Patients. Al-Kindy Col Med J 2012; 8:84-88.
9. Pego-Reigosa JM, Nicholson L, Pooley N, et al. The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis. Rheumatology 2021; 60:60-72.
10. Kusnanto K, Sari NP, Harmayetty H, et al. Self-care model application to improve self-care agency, self-care activities, and quality of life in patients with systemic lupus erythematosus. J Taibah Univ Medical Sci 2018; 13(5):472-478.
11. Fife BT, Pauken KE. The role of the PD‐1 pathway in autoimmunity and peripheral tolerance. Ann NY Acad Sci 2011; 1217:45-59.
12. Jubel JM, Barbati ZR, Burger C, et al. The role of PD-1 in acute and chronic infection. Front Immunol 2020; 11:487.
13. Al-Ammiri HH, Mohammed MM., Hussein AA. et al. Validity of Check Point Inhibitor (PD-1 and PD-L1) in Diagnosis of Gastric Adenocarcinoma Using Modified Tissue Elisa. Pakistan J. Medical Health Sci 2022;16:622-622
14. Deng Y, Huang F, Wang J. A narrative review of PD-1 and autoimmune diseases. Ann Blood 2022; 7:1-8.
15. Curran CS, Gupta S, Sanz I, Sharon E. PD-1 immunobiology in systemic lupus erythematosus. J Autoimmun 2019; 97:1-9.
16. Lee YH, Woo JH, Choi SJ, et al. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus 2009;18:9-15.
17. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016; 54:139-148.
18. Kuhn A, Bonsmann G, Anders HJ, et al. The diagnosis and treatment of systemic lupus erythematosus. Dtsch Arztebl Int 2015;112:423-432.
19. Prokunina L, Castillejo-López C, Öberg F, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002;32:666-669.
20. Reppert S, Zinser E, Holzinger C, et al. NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis. Eur J Immunol 2015;45:1426-1440.
21. Robbs BK, Cruz AL, Werneck MB, et al. Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors. Mol Cell Biol 2008; 28:7168-7181.
22. Rengarajan J, Tang B, Glimcher LH. NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naive TH cells. Nat Immunol 2002; 3:48-54.
23. Lee JU, Kim LK, Choi JM. Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases. Front Immunol 2018; 9:2747.
24. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
25. Mosaferi E, Gharamaleki NA, Farzadi L, et al. The study of HLA-G gene and protein expression in patients with recurrent miscarriage. Adv Pharm Bull 2019; 9:70-75.
26. Ghorbani P, Mollaei H, Arabzedeh S, et al. Upregulation of single nucleotide polymorphism of PD-1 gene (rs10204525) in chronic hepatitis B patients. Int Arch Med Microbiol 2019; 2:1-8.
27. Jiao Q, Liu C, Yang Z, et al. Upregulated PD-1 expression is associated with the development of systemic lupus erythematosus, but not the PD-1.1 allele of the PDCD1 gene. Int J Genom 2014; 2014:1-6
28. Chua KH, Lian LH, Sim XJ, Cheah TE, Lau TP. Association between PDCD1 gene polymorphisms and risk of systemic lupus erythematosus in three main ethnic groups of the Malaysian population. Int J Mol Sci 2015; 16:9794-9803.
29. Carter LL, Fouser LA, Jussif J, et al. PD‐1: PD‐L inhibitory pathway affects both CD4+ and CD8+ T cells and is overcome by IL‐2. Eur J Immunol 2002; 32:634-643.
30. Zamani MR, Aslani S, Salmaninejad A, et al. PD-1/PD-L and autoimmunity: a growing relationship. Cell Immunol 2016; 310:27-41.
31. Eissa E, Kandil R, El-Ghobashy N, et al. Association of disease activity with programmed cell death 1 and its ligand programmed cell death ligand 1 expressions in lupus patients. Indian J Rheumatol 2022; 17: 347-352.
32. Luo Q, Kong Y, Fu B, et al. Increased TIM-3+ PD-1+ NK cells are associated with the disease activity and severity of systemic lupus erythematosus. Clin Exp Med 2022; 22:47-56.
33. Bryan CM, Rocklin GJ, Bick MJ, et al. Computational design of a synthetic PD-1 agonist. Proc Natl Acad Sci 2021;118:1-9.
34. Bassiouni SA, Abdeen HM, Morsi HK, et al. Programmed death 1 (PD-1) serum level and gene expression in recent onset systemic lupus erythematosus patients. Egypt Rheumatol 2021;43:213-218.
35. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999;11:141-151.
36. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 2005;5: 472-484.
37. Xiao Y, Qureischi M, Dietz L, Vaeth M, Vallabhapurapu SD, Klein-Hessling S, et al. Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity. J Exp Med 2021; 218:1-22.
38. Rafael-Vidal C, Altabás I, Pérez N, et al. Calcineurin and systemic lupus erythematosus: the rationale for using calcineurin inhibitors in the treatment of lupus nephritis. Int J Mol Sci 2021; 22:1263.
2. Shedid NH., Hafez EA., Akram SA, et al. Ultrasonographic abnormalities of wrist and metacarpophalangeal joints in a cohort of Egyptian patients with systemic lupus erythematosus. Egypt. J. Intern. Med. 2019; 31:951-957
3. Abdul-Majeed NG. Antibodies to selected minor target anti-neutrophil cytoplasmic antigens in systemic lupus patients. J Fac Med Baghdad 2015; 57:231-235.
4. Lisnevskaia L, Murphy G, Isenberg d. Systemic lupus erythematosus. Lancet 2014;384:1878-88.
5. Abbas AH, Melconian AK, Ad’hiah AH. Role of Helicobacter pylori infection in etiology of systemic lupus erythematosus. Curr Res Microbiol Biotechnol 2017; 5:1285-1288.
6. Abdualkader SN, Al-Shaikly AW, Al-Mousawy KM, et al. Correlation between Interleukin-4 and Interleukin-6 and auto antibodies in Systemic Lupus Erythematosus. J Fac Med Baghdad 2009;51:416-418.
7. Abdulridha RH, Saud AM, Alosami MH. Evaluation of Interferon Alpha (IFN-α) in Women with Systemic Lupus Erythematosus in Iraq. Iraqi J Sci 2022; 63:4225-4233.
8. Al-Hammamy HR, Abd KH, Khalil IA, Mahdi BM. Human Leukocyte Antigens Assosiation with Systemic Lupus Arythematosus In Iraqi Patients. Al-Kindy Col Med J 2012; 8:84-88.
9. Pego-Reigosa JM, Nicholson L, Pooley N, et al. The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis. Rheumatology 2021; 60:60-72.
10. Kusnanto K, Sari NP, Harmayetty H, et al. Self-care model application to improve self-care agency, self-care activities, and quality of life in patients with systemic lupus erythematosus. J Taibah Univ Medical Sci 2018; 13(5):472-478.
11. Fife BT, Pauken KE. The role of the PD‐1 pathway in autoimmunity and peripheral tolerance. Ann NY Acad Sci 2011; 1217:45-59.
12. Jubel JM, Barbati ZR, Burger C, et al. The role of PD-1 in acute and chronic infection. Front Immunol 2020; 11:487.
13. Al-Ammiri HH, Mohammed MM., Hussein AA. et al. Validity of Check Point Inhibitor (PD-1 and PD-L1) in Diagnosis of Gastric Adenocarcinoma Using Modified Tissue Elisa. Pakistan J. Medical Health Sci 2022;16:622-622
14. Deng Y, Huang F, Wang J. A narrative review of PD-1 and autoimmune diseases. Ann Blood 2022; 7:1-8.
15. Curran CS, Gupta S, Sanz I, Sharon E. PD-1 immunobiology in systemic lupus erythematosus. J Autoimmun 2019; 97:1-9.
16. Lee YH, Woo JH, Choi SJ, et al. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus 2009;18:9-15.
17. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016; 54:139-148.
18. Kuhn A, Bonsmann G, Anders HJ, et al. The diagnosis and treatment of systemic lupus erythematosus. Dtsch Arztebl Int 2015;112:423-432.
19. Prokunina L, Castillejo-López C, Öberg F, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002;32:666-669.
20. Reppert S, Zinser E, Holzinger C, et al. NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis. Eur J Immunol 2015;45:1426-1440.
21. Robbs BK, Cruz AL, Werneck MB, et al. Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors. Mol Cell Biol 2008; 28:7168-7181.
22. Rengarajan J, Tang B, Glimcher LH. NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naive TH cells. Nat Immunol 2002; 3:48-54.
23. Lee JU, Kim LK, Choi JM. Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases. Front Immunol 2018; 9:2747.
24. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
25. Mosaferi E, Gharamaleki NA, Farzadi L, et al. The study of HLA-G gene and protein expression in patients with recurrent miscarriage. Adv Pharm Bull 2019; 9:70-75.
26. Ghorbani P, Mollaei H, Arabzedeh S, et al. Upregulation of single nucleotide polymorphism of PD-1 gene (rs10204525) in chronic hepatitis B patients. Int Arch Med Microbiol 2019; 2:1-8.
27. Jiao Q, Liu C, Yang Z, et al. Upregulated PD-1 expression is associated with the development of systemic lupus erythematosus, but not the PD-1.1 allele of the PDCD1 gene. Int J Genom 2014; 2014:1-6
28. Chua KH, Lian LH, Sim XJ, Cheah TE, Lau TP. Association between PDCD1 gene polymorphisms and risk of systemic lupus erythematosus in three main ethnic groups of the Malaysian population. Int J Mol Sci 2015; 16:9794-9803.
29. Carter LL, Fouser LA, Jussif J, et al. PD‐1: PD‐L inhibitory pathway affects both CD4+ and CD8+ T cells and is overcome by IL‐2. Eur J Immunol 2002; 32:634-643.
30. Zamani MR, Aslani S, Salmaninejad A, et al. PD-1/PD-L and autoimmunity: a growing relationship. Cell Immunol 2016; 310:27-41.
31. Eissa E, Kandil R, El-Ghobashy N, et al. Association of disease activity with programmed cell death 1 and its ligand programmed cell death ligand 1 expressions in lupus patients. Indian J Rheumatol 2022; 17: 347-352.
32. Luo Q, Kong Y, Fu B, et al. Increased TIM-3+ PD-1+ NK cells are associated with the disease activity and severity of systemic lupus erythematosus. Clin Exp Med 2022; 22:47-56.
33. Bryan CM, Rocklin GJ, Bick MJ, et al. Computational design of a synthetic PD-1 agonist. Proc Natl Acad Sci 2021;118:1-9.
34. Bassiouni SA, Abdeen HM, Morsi HK, et al. Programmed death 1 (PD-1) serum level and gene expression in recent onset systemic lupus erythematosus patients. Egypt Rheumatol 2021;43:213-218.
35. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999;11:141-151.
36. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 2005;5: 472-484.
37. Xiao Y, Qureischi M, Dietz L, Vaeth M, Vallabhapurapu SD, Klein-Hessling S, et al. Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity. J Exp Med 2021; 218:1-22.
38. Rafael-Vidal C, Altabás I, Pérez N, et al. Calcineurin and systemic lupus erythematosus: the rationale for using calcineurin inhibitors in the treatment of lupus nephritis. Int J Mol Sci 2021; 22:1263.
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Published
Mar 29, 2023
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Anwar Khalil Ismael, & Hazima Mossa Alabassi. (2023). PD-1 and NFATc1 as promising immunotherapy for SLE patients. Journal of Population Therapeutics and Clinical Pharmacology, 30(5), 260-266. https://doi.org/10.47750/jptcp.2023.30.05.025
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All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Anwar Khalil Ismael, & Hazima Mossa Alabassi. (2023). PD-1 and NFATc1 as promising immunotherapy for SLE patients. Journal of Population Therapeutics and Clinical Pharmacology, 30(5), 260-266. https://doi.org/10.47750/jptcp.2023.30.05.025