Investigating the Correlation between Growth Differentiation Factor 15 Serum Level and Its Gene Expression with Psoriasis and Its Severity
Abstract
Psoriasis is a chronic inflammatory dermatitis characterized by an inflammatory epidermal hyperproliferation. Growth differentiation factor‐15 (GDF-15), a member of the transforming growth factor‐β family, has immune modulatory roles in autoimmune condition of Psoriasis. This study aimed to evaluate the relationship between GDF-15 serum levels as well as gene expression with psoriasis and its severity.
This case-control study was performed on 45 patients with psoriasis Vulgaris and 45 healthy individuals. The severity of the disease was determined based on the psoriasis area and severity index (PASI score). Serum levels of GDF-15 were measured by enzyme-linked immunosorbent assay (ELISA) and its gene expression in peripheral blood mononuclear cells was quantified by real-time polymerase chain reaction (RT-PCR).
The mean serum levels of GDF-15 in patients and controls were 1.98±1.57 ng/mL and 0.93±0.48 ng/mL, respectively. GDF-15 gene expression was measured as 9.7±6.6% in the patient group and 7.6±2.5% in the healthy group. The mean of GDF-15 serum levels in mild, moderate, and severe cases of psoriasis were 0.45±0.35, 2.27±0.7, and 3.5±1.6 ng/mL, respectively, indicating that elevated serum levels of GDF-15 correlate significantly with disease severity. The mean of GDF-15 gene expression in the mild, moderate, and severe forms of psoriasis were 5.25±3.2, 7.6±2.8, and 17.8±5.7, respectively which indicate a significant relationship between GDF-15 gene expression and psoriasis severity.
Based on this study, in psoriatic patients, GDF-15 serum levels and gene expression are significantly higher than those in healthy controls. Such values were correlated with disease activity, especially in severe cases. Therefore, GDF-15 may be used as a prognostic marker of psoriasis.
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4. Farshchian M, Ansar A, Sobhan M, Hoseinpoor V. C-reactive protein serum level in patients with psoriasis before and after treatment with narrow-band ultraviolet B. An Bras Dermatol. 2016;91(5):580-83.
5. Krueger J G, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis. 2005;64(Suppl 2):ii30-6.
6. Desmedt S, Desmedt V, De Vos L, Delanghe JR, Speeckaert R, Speeckaert MM. Growth differentiation factor 15: A novel biomarker with high clinical potential. Crit Rev Clin Lab Sci. 2019;56(5):333-50.
7. Adela R, Banerjee SK. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J Diabetes Res. 2015;2015:490842.
8. Zimmers T, A, Jin X, Hsiao EC, McGrath SA, Esquela AF, Koniaris LG. Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 2005;23(6):543-8.
9. Emmerson PJ, Wang F, Du Y, Liu Q, Pickard RT, GonciarzMD, et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat Med. 2017;23(10):1215-19.
10. Luan HH, Wang A, Hilliard BK, Carvalho F, Rosen CE, Ahasic AM,et al. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell. 2019;178(5):1231-44.
11. Breit SN, Johnen H, Cook AD, Tsai VW, Mohammad MG, Kuffner T, et al. The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors. 2011;29(5):187-95.
12. Zarbock A, Kempf T, Wollert KC, Vestweber D. Leukocyte integrin activation and deactivation: novel mechanisms of balancing inflammation. J Mol Med (Berl). 2012;90(4):353-9.
13. Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment. J Am Acad Dermatol. 2004;51(4):563-9.
14. Shuang Li, Qing-Zhao Zhang, De-Qin Zhang, et al. GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation. Mol Med Rep. 2017;15(6):3599–06.
15. Osman T, Mustafa AS, İbrahim B, et al. Serum GDF-15 level in rheumatoid arthritis: relationship with disease activity and subclinical atherosclerosis.Acta Reumatol Port. 2017;42(1):66-72.
16. Esalatmanesh K, Fayyazi H, Esalatmanesh R, Khabbazi A. The association between serum levels of growth differentiation factor-15 and rheumatoid arthritis activity. Int J Clin Pract. 2020;74(9):e13564
17. Brown D A, Moore J, Johnen H, Smeets TJ, Bauskin AR, Kuffner T, et al. Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of erosive joint destruction. Arthritis Rheum. 2007;56(3):753-64.
18. Bauskin AR, Jiang L, Luo XW, Wu L, Brown DA, Breit SN. The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores. J Interferon Cytokine Res. 2010;30(6):389-97.
19. Gamal SM, Elgengehy FT, Kamal A, El Bakry SA, Shabaan E, Elgendy A, Bassyouni IH. Growth Differentiation Factor-15 GDF-15) Level and Relation to Clinical Manifestations in Egyptian Systemic Sclerosis patients: Preliminary Data. Immunol Invest. 2017;46(7):703-13.
20. Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S. Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis: association with disease severity. Mod Rheumatol. 2012;22(5):668-75.
21. Suesskind D, Schatz A, Schnichels S, Coupland SE, Lake SL, Wissinger B, et al. GDF-15: a novel serum marker for metastases in uveal melanoma patients. Graefes Arch Clin Exp Ophthalmol. 2012;250(6):887-95.
22. Gkretsi V, LoucaM, Stylianou A, Minadakis G, Spyrou GM, Stylianopoulos T. Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15). Int J Mol Sci. 2019;20(1):163-9.
23. Bao X, Borné Y, Muhammad IF, Nilsson J, Lind L, Melander O, et al. Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort. Diabetologia. 2019;62(1):78-86.
24. Zhang, Y., Jiang, M., Nouraie M, Roth MG, Tabib T, Winters S,et al. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2019;317(4):L510-L521.
25. De Paepe B, Verhamme F, De Bleecker JL. The myokine GDF-15 is a potential biomarker for myositis and associates with the protein aggregates of sporadic inclusion body myositis. Cytokine. 2020;127:154966.
26. Song Y, Cui Y, Zhang X, Lin H, Zhang G, Zeng H, et al. Increased serum levels of MIC1/GDF15 correlated with bone erosion in spondyloarthritis: A pilot study. Medicine (Baltimore). 2018;97(51):e13733.Sarıyıldız MA, Yazmalar L, Batmaz İ, Alpaycı M, Burkan YK, Sula B, et al. Serum GDF-15 level in Behçet's disease: relationships between disease activity and clinical parameters. Int J Dermatol. 2016;55(11):1289-94.
27. Ali G, Elsayed AK, Nandakumar M, Bashir M, Younis I, Abu Aqel Y, et al. Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease. Stem Cells Dev. 2020;29(7):383-400.
28. Widera C, Giannitsis E, Kempf T, Korf-Klingebiel M, Fiedler B, Sharma S, et al. Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome. Clin Chem. 2012;58(8):1233-41.
29. Wischhusen J, Melero I, Fridman WH. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020;11:951.
30. Artz A, Butz S, Vestweber D. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer. Blood. 2016;128(4):529-41. Wu Q, Jiang D, Schaefer NR, Harmacek L, O'Connor BP, Eling TE,et al. Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung. Am J Physiol Lung Cell Mol Physiol. 2018;314(3):L514-L527.
31. Shao Y, Wang H, Liu C, Cao Q, Fu R, Wang H, et al. Transforming growth factor 15 increased in severe aplastic anemia patients. Hematology. 2017;22(9):548-53.Fang L, Li F, Gu C. GDF-15: A Multifunctional Modulator and Potential Therapeutic Target in Cancer. Curr Pharm Des. 2019;25(6):654-62.
2. Arisi R, Iskandar IYK, Kontopantelis E, Augustin M, Griffiths CEM, Ashcroft DM; Global Psoriasis Atlas. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study. BMJ. 2020;369(14):96-102
3. Jiang S, Hinchliffe TE, Wu T. Biomarkers of An Autoimmune Skin Disease--Psoriasis. Genomics Proteomics Bioinformatics. 2015;13(4):224-33.
4. Farshchian M, Ansar A, Sobhan M, Hoseinpoor V. C-reactive protein serum level in patients with psoriasis before and after treatment with narrow-band ultraviolet B. An Bras Dermatol. 2016;91(5):580-83.
5. Krueger J G, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis. 2005;64(Suppl 2):ii30-6.
6. Desmedt S, Desmedt V, De Vos L, Delanghe JR, Speeckaert R, Speeckaert MM. Growth differentiation factor 15: A novel biomarker with high clinical potential. Crit Rev Clin Lab Sci. 2019;56(5):333-50.
7. Adela R, Banerjee SK. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J Diabetes Res. 2015;2015:490842.
8. Zimmers T, A, Jin X, Hsiao EC, McGrath SA, Esquela AF, Koniaris LG. Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 2005;23(6):543-8.
9. Emmerson PJ, Wang F, Du Y, Liu Q, Pickard RT, GonciarzMD, et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat Med. 2017;23(10):1215-19.
10. Luan HH, Wang A, Hilliard BK, Carvalho F, Rosen CE, Ahasic AM,et al. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell. 2019;178(5):1231-44.
11. Breit SN, Johnen H, Cook AD, Tsai VW, Mohammad MG, Kuffner T, et al. The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors. 2011;29(5):187-95.
12. Zarbock A, Kempf T, Wollert KC, Vestweber D. Leukocyte integrin activation and deactivation: novel mechanisms of balancing inflammation. J Mol Med (Berl). 2012;90(4):353-9.
13. Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment. J Am Acad Dermatol. 2004;51(4):563-9.
14. Shuang Li, Qing-Zhao Zhang, De-Qin Zhang, et al. GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation. Mol Med Rep. 2017;15(6):3599–06.
15. Osman T, Mustafa AS, İbrahim B, et al. Serum GDF-15 level in rheumatoid arthritis: relationship with disease activity and subclinical atherosclerosis.Acta Reumatol Port. 2017;42(1):66-72.
16. Esalatmanesh K, Fayyazi H, Esalatmanesh R, Khabbazi A. The association between serum levels of growth differentiation factor-15 and rheumatoid arthritis activity. Int J Clin Pract. 2020;74(9):e13564
17. Brown D A, Moore J, Johnen H, Smeets TJ, Bauskin AR, Kuffner T, et al. Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of erosive joint destruction. Arthritis Rheum. 2007;56(3):753-64.
18. Bauskin AR, Jiang L, Luo XW, Wu L, Brown DA, Breit SN. The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores. J Interferon Cytokine Res. 2010;30(6):389-97.
19. Gamal SM, Elgengehy FT, Kamal A, El Bakry SA, Shabaan E, Elgendy A, Bassyouni IH. Growth Differentiation Factor-15 GDF-15) Level and Relation to Clinical Manifestations in Egyptian Systemic Sclerosis patients: Preliminary Data. Immunol Invest. 2017;46(7):703-13.
20. Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S. Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis: association with disease severity. Mod Rheumatol. 2012;22(5):668-75.
21. Suesskind D, Schatz A, Schnichels S, Coupland SE, Lake SL, Wissinger B, et al. GDF-15: a novel serum marker for metastases in uveal melanoma patients. Graefes Arch Clin Exp Ophthalmol. 2012;250(6):887-95.
22. Gkretsi V, LoucaM, Stylianou A, Minadakis G, Spyrou GM, Stylianopoulos T. Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15). Int J Mol Sci. 2019;20(1):163-9.
23. Bao X, Borné Y, Muhammad IF, Nilsson J, Lind L, Melander O, et al. Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort. Diabetologia. 2019;62(1):78-86.
24. Zhang, Y., Jiang, M., Nouraie M, Roth MG, Tabib T, Winters S,et al. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2019;317(4):L510-L521.
25. De Paepe B, Verhamme F, De Bleecker JL. The myokine GDF-15 is a potential biomarker for myositis and associates with the protein aggregates of sporadic inclusion body myositis. Cytokine. 2020;127:154966.
26. Song Y, Cui Y, Zhang X, Lin H, Zhang G, Zeng H, et al. Increased serum levels of MIC1/GDF15 correlated with bone erosion in spondyloarthritis: A pilot study. Medicine (Baltimore). 2018;97(51):e13733.Sarıyıldız MA, Yazmalar L, Batmaz İ, Alpaycı M, Burkan YK, Sula B, et al. Serum GDF-15 level in Behçet's disease: relationships between disease activity and clinical parameters. Int J Dermatol. 2016;55(11):1289-94.
27. Ali G, Elsayed AK, Nandakumar M, Bashir M, Younis I, Abu Aqel Y, et al. Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease. Stem Cells Dev. 2020;29(7):383-400.
28. Widera C, Giannitsis E, Kempf T, Korf-Klingebiel M, Fiedler B, Sharma S, et al. Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome. Clin Chem. 2012;58(8):1233-41.
29. Wischhusen J, Melero I, Fridman WH. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020;11:951.
30. Artz A, Butz S, Vestweber D. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer. Blood. 2016;128(4):529-41. Wu Q, Jiang D, Schaefer NR, Harmacek L, O'Connor BP, Eling TE,et al. Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung. Am J Physiol Lung Cell Mol Physiol. 2018;314(3):L514-L527.
31. Shao Y, Wang H, Liu C, Cao Q, Fu R, Wang H, et al. Transforming growth factor 15 increased in severe aplastic anemia patients. Hematology. 2017;22(9):548-53.Fang L, Li F, Gu C. GDF-15: A Multifunctional Modulator and Potential Therapeutic Target in Cancer. Curr Pharm Des. 2019;25(6):654-62.
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| Issue | Vol 20 No 5 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i5.7409 | |
| Keywords | ||
| Growth differentiation factor 15 Psoriasis | ||
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How to Cite
1.
Akbari H, Talaee R, Zaker SF, Nikoueinejad H. Investigating the Correlation between Growth Differentiation Factor 15 Serum Level and Its Gene Expression with Psoriasis and Its Severity. Iran J Allergy Asthma Immunol. 2021;20(5):593-599.
