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IL-10 and IL-17 Gene Polymorphisms in Adult Idiopathic Thrombocytopenic Purpura

Yıl 2018, Cilt: 6 Sayı: 2, 36 - 44, 12.09.2018

Öz

Objective: Interleukin 10 (IL-10) and
interleukin 17 (il-17) cytokine gene polymorphisms were investigated in many
autoimmune diseases and there were significant results in some studies but
there were a few published studies on IL-10 and il-17 gene polymorphisms in
idiopathic
thrombocytopenic purpura ( ITP).
In this study, we aimed to evaluate the IL-10 (-592 A/C) and IL-17
(A126G) gene polymorphisms and their serum levels in adult patients with ITP.

Materials and Methods: The IL-10 (-592
A/C) and IL-17 (A126G) gene polymorphisms in 50 patients with ITP and 51
healthy control groups were determined after DNA isolation and serum levels of
these cytokines were measured by ELISA method in 32 patients with ITP and 32
healthy volunteers.

Results: There was no statistically
significant difference in IL-10 (-592 A/C) and IL-17 (A126G) gene polymorphisms
between the patients and control groups, whereas serum IL-10 levels were found
to be statistically significant higher in ITP patients than control group
(p=0.003).
Serum IL-17 levels were similar in patients
and control groups. In addition, age, sex, response to treatment and platelet
values at diagnosis were compared between the groups, but there was no
statistically significant difference between the groups.







Conclusion: In our study, IL-10 (-592
A/C) and IL-17 (A126G) gene polymorphisms were not found to be different in
patients with ITP compared to healthy subjects, although IL-10 levels were
found to be higher in the ITP group than healthy group.
When we look the datas in the literature, we think that more
studies with larger series are needed in this field in order to clarify the
importance of cytokines in the diagnosis and follow-up of ITP.

Kaynakça

  • 1. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017; 129(21):2829–35.
  • 2. Semple J.W., Provan D. The immunopathogenesis of immune thrombocytopenia: T cells still take center-stage Curr Opinion Hematol. 2012;19:357-62
  • 3. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5-17.
  • 4. Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90:914-23.
  • 5. Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/ Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71:283-8.
  • 6. Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, et al. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica. 2011;96:1560-4.
  • 7. ZhouL,XuF,ChangC,TaoY,SongL,LiX. Interleukin-17-producing CD4+T lymphocytes are increased in the patients with primary immune thrombocytopenia. Blood Coagul Fibrinolysis. 2016;27:301-7.
  • 8. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226:205-18
  • 9. Zhang G, Zhang P, Liu H, Liu X, Xie S, Wang X, et al. Assessment of Th17/Treg cells and Th cytokines in an improved immune thrombocytopenia mouse model. Hematology. 2017;22:493-500.
  • 10. Rezaeeyan H, Jaseb K, Alghasi A, Asnafi AA, Saki N. Association between gene polymorphisms and clinical features in idiopathic thrombocytopenic purpura patients. Blood Coagul Fibrinolysis 2017;28:617-22.
  • 11. Pehlivan M, Okan V, Sever T, Balci SO, Yilmaz M, Babacan T, et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets. 2011;22(8):588-95.
  • 12. Saitoh T, Kasamatsu T, Inoue M, Mitsui T, Koiso H, Yokohama A, et al. Interleukin-10 gene polymorphism reflects the severity of chronic immune thrombocytopenia in Japanese patients. Int J Lab Hematol. 2011;33:526-32.
  • 13. Wu KH, Peng CT, Li TC, Wan L, Tsai CH, Lan SJ, Chang MC, Tsai FJ. Interleukin 4, interleukin 6 and interleukin 10 polymorphisms in children with acute and chronic immune thrombocytopenic purpura. Br J Haematol. 2005;128(6):849-52.
  • 14. Khalilzadeh O, Anvari M, Momen-Heravi F, Esteghamati A, Rashidi A, Mahmoudi M, et al. Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease. Clin Exp Med. 2010;10(2):123–8.
  • 15. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S. Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int. 2010; 30(9):1211–7.
  • 16. Jang WC, Nam YH, Ahn YC, Lee SH, Park SH, Choe JY, et al. Interleukin-17F gene polymorphisms in Korean patients with Behçet's disease. Rheumatol Int. 2008;29:173-8.
  • 17. Ma D, Zhu X, Zhao P, Zhao C, Li X, Zhu Y, et al. Profile of Th17 cytokines (IL-17, TGFbeta, IL-6) and Th1 cytokine (IFN-gamma) in patients with immune thrombocytopenic purpura. Ann Hematol 2008;87:899-904.
  • 18. Ji L, Zhan Y, Hua F, Li F, Zou S, Wang W, et al. The ratio of treg/th17 cells correlates with the disease activity of primary immune thrombocytopenia. PLoS One. 2012; 7:e50909.
  • 19. Hu Y, Ma DX, Shan NN, Zhu YY, Liu XG, Zhang L, et al. Increased number of Tc17 and correlation with Th17 cells in patients with immune thrombocytopenia. PLoS One. 2011;6:e26522.
  • 20. Zhang J, Ma D, Zhu X, Qu X, Ji C, Hou M. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica. 2009;94:1326-9.
  • 21. Li F, Ji L, Wang W, Hua F, Zhan Y, Zou S, et al. Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients. Immunol Res. 2015;61:269-80.
  • 22. Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, et al. Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol. 2007; 78:139-43.
  • 23. Tesse R, Del Vecchio GC, De Mattia D, Sangerardi M, Valente F, Giordano P. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. Gene. 2012;505:53-6.
  • 24. Saitoh T, Tsukamoto N, Koiso H, Mitsui T, Yokohama A, Handa H, et al. Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia. Eur J Haematol. 2011;87(3);253-8.
  • 25. Culic S, Labar B, Marusic A, Salamunic I. Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura. Pediatr Blood Cancer. 2006; 47:671-4.
  • 26. Wang JD, Chang TK, Lin HK, Huang FL, Wang CJ, Lee HJ. Reduced expression of transforming growth factor‐β1 and correlated elevation of interleukin‐17 and interferon‐γ in pediatric patients with chronic primary immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2011;57:636-40.
  • 27. Guo NH, Shi QZ, Hua JY, Li ZJ, Li J, He WF, et al. Expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura and its significance. Zhonghua Xue Ye Xue Za Zhi. 2010;31(9):610-12.
  • 28. Chang DY, Ouyang J, Zhou RF, Xu JY, Chen B, Yang YG, Zhang QG, Shao XY, Guan CY, Xu Y: Profiles of different subsets of CD(4)(+) T cells in chronic idiopathic thrombocytopenic purpura. Zhonghua Nei Ke Za Zhi. 2010;49(3):213-6.
  • 29. Wang X, Zhou YH, Chen XH, Yin LM, Zhao YN, Wo, LK, et al. Role and Significance of T Help Cells 17 in Pathogenesis of Idiopathic Thrombocytopenic Purpura. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016; 24(6):1833-36.
  • 30. Qiao J, Li X, Wu Y, Wu X, Zhu F, Liu N, et al. An increased expression profile of Th9/IL-9 correlated with Th17/IL-17 in patients with immune thrombocytopenia. Platelets. 2017;28(3);287-94.

Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm

Yıl 2018, Cilt: 6 Sayı: 2, 36 - 44, 12.09.2018

Öz

Amaç: İnterlökin 10 (IL-10) ve interlökin 17 (IL-17) sitokin
gen polimorfizmlerinin
otoimmün birçok hastalıkta araştırıldığı ve bazılarında
anlamlı sonuçlar bulunduğu ancak
idiyopatik
trombositopenik purpura

(ITP) hastalarda
IL-10 ve IL-17 gen polimorfizmleri ile ilgili yayınlanmış az sayıda çalışma mevcut olduğu görülmüştür. Bu çalışmada erişkin ITP hastalarında IL-10 (-592 A/C) ve IL-17 (A126G) gen
polimorfizmi ve bu sitokinlerin
serum düzeylerinin
değerlendirilmesi amaçlanmıştır.



Materyal
ve Metot
: 50 ITP’ li hasta ve 51 sağlıklı kontrol
grubunda IL-10 (-592 A/C) ve IL-17 (A126G) gen polimorfizmleri, DNA izolasyonu
yapıldıktan sonra belirlenmiş ve bu sitokinlerin serum düzeyleri ELİSA yöntemi
ile toplam 32 ITP’li hastada ve 32 sağlıklı kişide ölçülmüştür.



Bulgular: Hasta
ve kontrol grupları arasında IL-10 (-592 A/C) ve IL-17 (A126G) gen
polimorfizmleri dağılımı açısından istatistiksel olarak anlamlı fark
bulunmazken, serum IL-10 düzeyleri ITP’li hastalarda sağlıklı bireylere göre
istatistiksel olarak anlamlı derecede yüksek bulunmuştur (p=0,003). Serum IL-17
düzeyleri ise hasta ve kontrol grubunda benzer bulunmuştur. Ayrıca gruplar
arasında yaş, cinsiyet, tedavi cevabı, tanı anıdaki trombosit değerleri
karşılaştırılmış ancak gruplar arasında istatistiksel olarak anlamlı fark
saptanmamıştır.



Sonuç: Çalışmamızda ITP’li hastalarda sağlıklı kişilere göre IL-10 (-592
A/C) ve IL-17 (A126G) gen polimorfizmleri sıklıklarının farklı olduğu
saptanamasa da IL-10 düzeyleri ITP’li grupta yüksek bulunmuştur. Sitokinlerin
ITP’nin tanı ve takibindeki önemini açıklığa kavuşturabilmek için literatürdeki
veriler de dikkate alındığında bu alanda daha geniş hasta serili çalışmalara
ihtiyaç olduğunu düşünmekteyiz

Kaynakça

  • 1. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017; 129(21):2829–35.
  • 2. Semple J.W., Provan D. The immunopathogenesis of immune thrombocytopenia: T cells still take center-stage Curr Opinion Hematol. 2012;19:357-62
  • 3. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5-17.
  • 4. Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90:914-23.
  • 5. Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/ Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71:283-8.
  • 6. Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, et al. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica. 2011;96:1560-4.
  • 7. ZhouL,XuF,ChangC,TaoY,SongL,LiX. Interleukin-17-producing CD4+T lymphocytes are increased in the patients with primary immune thrombocytopenia. Blood Coagul Fibrinolysis. 2016;27:301-7.
  • 8. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226:205-18
  • 9. Zhang G, Zhang P, Liu H, Liu X, Xie S, Wang X, et al. Assessment of Th17/Treg cells and Th cytokines in an improved immune thrombocytopenia mouse model. Hematology. 2017;22:493-500.
  • 10. Rezaeeyan H, Jaseb K, Alghasi A, Asnafi AA, Saki N. Association between gene polymorphisms and clinical features in idiopathic thrombocytopenic purpura patients. Blood Coagul Fibrinolysis 2017;28:617-22.
  • 11. Pehlivan M, Okan V, Sever T, Balci SO, Yilmaz M, Babacan T, et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets. 2011;22(8):588-95.
  • 12. Saitoh T, Kasamatsu T, Inoue M, Mitsui T, Koiso H, Yokohama A, et al. Interleukin-10 gene polymorphism reflects the severity of chronic immune thrombocytopenia in Japanese patients. Int J Lab Hematol. 2011;33:526-32.
  • 13. Wu KH, Peng CT, Li TC, Wan L, Tsai CH, Lan SJ, Chang MC, Tsai FJ. Interleukin 4, interleukin 6 and interleukin 10 polymorphisms in children with acute and chronic immune thrombocytopenic purpura. Br J Haematol. 2005;128(6):849-52.
  • 14. Khalilzadeh O, Anvari M, Momen-Heravi F, Esteghamati A, Rashidi A, Mahmoudi M, et al. Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease. Clin Exp Med. 2010;10(2):123–8.
  • 15. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S. Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int. 2010; 30(9):1211–7.
  • 16. Jang WC, Nam YH, Ahn YC, Lee SH, Park SH, Choe JY, et al. Interleukin-17F gene polymorphisms in Korean patients with Behçet's disease. Rheumatol Int. 2008;29:173-8.
  • 17. Ma D, Zhu X, Zhao P, Zhao C, Li X, Zhu Y, et al. Profile of Th17 cytokines (IL-17, TGFbeta, IL-6) and Th1 cytokine (IFN-gamma) in patients with immune thrombocytopenic purpura. Ann Hematol 2008;87:899-904.
  • 18. Ji L, Zhan Y, Hua F, Li F, Zou S, Wang W, et al. The ratio of treg/th17 cells correlates with the disease activity of primary immune thrombocytopenia. PLoS One. 2012; 7:e50909.
  • 19. Hu Y, Ma DX, Shan NN, Zhu YY, Liu XG, Zhang L, et al. Increased number of Tc17 and correlation with Th17 cells in patients with immune thrombocytopenia. PLoS One. 2011;6:e26522.
  • 20. Zhang J, Ma D, Zhu X, Qu X, Ji C, Hou M. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica. 2009;94:1326-9.
  • 21. Li F, Ji L, Wang W, Hua F, Zhan Y, Zou S, et al. Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients. Immunol Res. 2015;61:269-80.
  • 22. Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, et al. Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol. 2007; 78:139-43.
  • 23. Tesse R, Del Vecchio GC, De Mattia D, Sangerardi M, Valente F, Giordano P. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. Gene. 2012;505:53-6.
  • 24. Saitoh T, Tsukamoto N, Koiso H, Mitsui T, Yokohama A, Handa H, et al. Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia. Eur J Haematol. 2011;87(3);253-8.
  • 25. Culic S, Labar B, Marusic A, Salamunic I. Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura. Pediatr Blood Cancer. 2006; 47:671-4.
  • 26. Wang JD, Chang TK, Lin HK, Huang FL, Wang CJ, Lee HJ. Reduced expression of transforming growth factor‐β1 and correlated elevation of interleukin‐17 and interferon‐γ in pediatric patients with chronic primary immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2011;57:636-40.
  • 27. Guo NH, Shi QZ, Hua JY, Li ZJ, Li J, He WF, et al. Expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura and its significance. Zhonghua Xue Ye Xue Za Zhi. 2010;31(9):610-12.
  • 28. Chang DY, Ouyang J, Zhou RF, Xu JY, Chen B, Yang YG, Zhang QG, Shao XY, Guan CY, Xu Y: Profiles of different subsets of CD(4)(+) T cells in chronic idiopathic thrombocytopenic purpura. Zhonghua Nei Ke Za Zhi. 2010;49(3):213-6.
  • 29. Wang X, Zhou YH, Chen XH, Yin LM, Zhao YN, Wo, LK, et al. Role and Significance of T Help Cells 17 in Pathogenesis of Idiopathic Thrombocytopenic Purpura. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016; 24(6):1833-36.
  • 30. Qiao J, Li X, Wu Y, Wu X, Zhu F, Liu N, et al. An increased expression profile of Th9/IL-9 correlated with Th17/IL-17 in patients with immune thrombocytopenia. Platelets. 2017;28(3);287-94.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Tuğba Songül Tat 0000-0001-6752-320X

Mustafa Yılmaz Bu kişi benim

Ahmet Alver

Gülşah Bayçelebi Bu kişi benim

Yayımlanma Tarihi 12 Eylül 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 6 Sayı: 2

Kaynak Göster

APA Tat, T. S., Yılmaz, M., Alver, A., Bayçelebi, G. (2018). Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm. Namık Kemal Tıp Dergisi, 6(2), 36-44.
AMA Tat TS, Yılmaz M, Alver A, Bayçelebi G. Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm. NKMJ. Eylül 2018;6(2):36-44.
Chicago Tat, Tuğba Songül, Mustafa Yılmaz, Ahmet Alver, ve Gülşah Bayçelebi. “Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 Ve IL-17 Gen Polimorfizm”. Namık Kemal Tıp Dergisi 6, sy. 2 (Eylül 2018): 36-44.
EndNote Tat TS, Yılmaz M, Alver A, Bayçelebi G (01 Eylül 2018) Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm. Namık Kemal Tıp Dergisi 6 2 36–44.
IEEE T. S. Tat, M. Yılmaz, A. Alver, ve G. Bayçelebi, “Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm”, NKMJ, c. 6, sy. 2, ss. 36–44, 2018.
ISNAD Tat, Tuğba Songül vd. “Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 Ve IL-17 Gen Polimorfizm”. Namık Kemal Tıp Dergisi 6/2 (Eylül 2018), 36-44.
JAMA Tat TS, Yılmaz M, Alver A, Bayçelebi G. Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm. NKMJ. 2018;6:36–44.
MLA Tat, Tuğba Songül vd. “Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 Ve IL-17 Gen Polimorfizm”. Namık Kemal Tıp Dergisi, c. 6, sy. 2, 2018, ss. 36-44.
Vancouver Tat TS, Yılmaz M, Alver A, Bayçelebi G. Erişkin İdiyopatik Trombositopenik Purpuralı Hastalarda IL-10 ve IL-17 Gen Polimorfizm. NKMJ. 2018;6(2):36-44.