Aktif ve inaktif Behçet hastalığında serum hepsidin düzeyleri

Yıl 2019, , 63 - 72, 31.03.2019

Okan Dikker , Sembol Yıldırmak Mustafa Şahin , Murat Usta Müberra Vardar Eren Vurgun , Yüksel Çiçek Mustafa Durmuşcan Zeynep Altun Fehmi Baran

https://doi.org/10.21601/ortadogutipdergisi.413997

Öz

Amaç: Bu çalışmada, inflamasyona yanıt olarak hepsidin sentezindeki değişimin değerlendirilmesi ve inflamatuar bir hastalık olan Behçet hastalığında (BH) hepsidin ve akut faz reaktanları arasındaki ilişkiyi ortaya koymak amaçlandı. 

Gereç ve Yöntemler: Çalışmaya 52 BH (15 aktif, 37 inaktif hasta) 13 izole demir eksikliği anemisi hastası, 13 sağlıklı kontrol, toplamda 78 katılımcı dâhil edildi. Kronik hastalık anemili hastaların 3'ü aktif, 1'i inaktif behçet hastasıydı. ELISA yöntemiyle biyoaktif hepsidin-25 düzeylerini ölçüldü.

Bulgular: İnaktif BH ve ana BH gruplarında sağlıklı kontrollere göre anlamlı derecede düşük hepsidin düzeyleri saptandı (sırasıyla p=0.015, p=0.014); hepsidin düzeylerini, kronik hastalık anemisi olan BH grubu ile sağlıklı kontroller ve izole demir eksikliği anemisi grubu karşılaştırıldığında ve istatistiksel olarak anlamlı sonuç elde edildi. (sırasıyla p=0.007, p=0.003). Ayrıca aktif BD grubunun hepcidin düzeyleri ile sağlıklı kontroller arasında anlamlı bir fark bulunamadı (p> 0.05).

Sonuç: İnflamasyondaki artış paterninin aksine, Behçet hastalarında artmış hepsidin seviyelerini tespit edilmedi. Hepsidin seviyelerini etkileyen antiinflamatuar tedavilerin serum İnterlökin-6 (IL-6) düzeylerini değiştirdiğinden, daha önce teşhis edilmiş ve/veya daha önce tedavi almayan Behçet hastalarının IL-6 düzeyleri ile birlikte hepsidin düzeylerinin ölçümü ve değerlendirilmesi gerekmektedir.

Anahtar Kelimeler

Behçet hastalığı, kronik hastalık anemisi, hepsidin

Serum hepcidin levels in active and inactive Behcet’s disease

Öz

Aim: This study aims to evaluate the alteration of hepcidin synthesis in response to inflammation and to reveal the relationship between hepcidin and acute phase reactants in Behcet’s disease (BD) which is also an inflammatory disease.

Material and Methods: That was included 52 BD patients (15 with active, 37 with inactive disease), 13 isolated iron deficiency anemia patients and 13 healthy controls; totally 78 individuals to the study. Patients with chronic disease anemia had 3 active and 1 inactive Behcet's disease. Levels of bioactive hepcidin-25 were measured by ELISA method. 

Result: Low hepcidin levels were found significantly in inactive BD and the main BD groups comparing to healthy controls (p=0.015, p=0.014, respectively); in BD with anemia of chronic disease group comparing to healthy controls and isolated iron deficiency anemia group (p=0.007, p=0.003, respectively). Besides it was not found any significant difference between hepcidin levels of active BD group and healthy controls (p>0.05). 

Conclusion: Contrary to its increment pattern in inflammation, increased hepcidin levels in Behcet’s patients were not detected. Alternation of serum Interleukin-6 (IL-6) levels with anti-inflammatory treatments affecting hepcidin levels necessitate hepcidin measurement only in Behcet’s patients who have been recently diagnosed and/or haven't received a treatment before and evaluation of the measurement together with IL-6 levels.

Anahtar Kelimeler

Behcet’s disease, anemia of chronic disease, hepcidin

Kaynakça

• 1. Erkilic K, Evereklioglu C, Cekmen M, Ozkiris A, Duygulu F, Dogan H. Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behcet’s disease: original contributions/clinical and laboratory investigations. Mediators Inflamm 2003; 12: 107-16.
• 2. Behcet H. Uber rezidivivierende aphthose, durchein virus verursachte geschwure am mund, am auge und an den genitalien. Dermatol Wochenschr 1937; 105: 1152-57.
• 3. Ghate JV, Jorizzo JL. Behcet’s disease and complex aphthosis. J Am Acad Dermatol 1999; 40: 1-18.
• 4. Jorizzo JL, Hudson RD, Schmalstieg FC, Daniels JC, Apisarnthanarax P, Henry JC, et al. Behcet’s syndrome: immune regulation, circulating immune complexes, neutrophil migration and colchicine therapy. J Am Acad Dermatol 1984; 10: 205-14.
• 5. Sandıkcı R, Turkmen S, Guvenen G et al. Lipid peroxidation and antioxidant defence system in patients with active and inactive Behcet’s disease. Acta Derm Venereol 2003; 83: 342-46.
• 6. Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Textbook of dermatogy. 6th Ed. London 1998; 3072-74.
• 7. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev 2002; 16: 87-96.
• 8. Means RT Jr. Recent developments in the anemia of chronic disease. Curr Hematol Rep 2003; 2: 116-21.
• 9. Schranz M, Bakry R, Creus M, Bonn G, Vogel W, Zoller H. Activation and inactivation of the iron hormone hepcidin: Biochemical characterization of prohepcidin cleavage and sequential degradation to N-terminally truncated hepcidin isoforms. Blood Cells Mol Dis 2009; 43: 169-79.
• 10. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003; 102: 783-8.
• 11. Małyszko J, Małyszko JS, Hryszko T, Pawlak K, Mysliwiec M. Is hepcidin a link between anemia, inflammation and liver function in hemodialyzed patients?. Am J Nephrol 2005; 25: 586-90.
• 12. Koca S, Isik A, Ustundag B, Metin K, Aksoy K. Serum Pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus. Inflammation 2008; 31: 146-53.
• 13. International study group for Behcet’s disease. Criteria for diagnosis Behcet’s disease. Lancet 1990; 335: 1078-80.
• 14. Odabas AR, Karakuzu A, Cetinkaya R, Selcuk Y, Keles S, Bilen H. Increased serum ferritin levels in active Behcet’s disease. Int J Clin Pract 2002; 56: 310-11.
• 15. Bayazit N, Yilmaz M, Oral B et al. Behcet hastalıgında immünolojik aktivasyon belirteçleri. Turk J Dermatol 2008; 2: 34-8.
• 16. Izaks GJ, Westendorp RG, Knook DL. The definition of anemia in older persons. JAMA 1999; 281: 1714-7.
• 17. Richer SA. A Practical guide for differentiating between iron deficiency anemia and anemia of chronic disease in children and adults. Nurse Pract 1997; 22: 55
• 18. Vreugdenhil G, Baltus CA, Van Eijk HG, Swaak AJ. Anaemia of chronic disease: diagnostic significance of erythrocyte and serological parameters in iron deficient rheumatoid arthritis patients. Br J Rheumatol 1990; 29: 105-10.
• 19. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003; 101: 2461–63.
• 20. Dallalio G, Fleury T, Means RT. Serum hepcidin in clinical specimens. Br J Haematol 2003; 122: 996–1000.
• 21. Taes YE, Wuyts B, Boelaert JR, De VrieseAS, Delanghe JR. Prohepcidin accumulates in renal insufficiency. Clin Chem Lab Med 2004; 42: 387–89.
• 22. Roe MA, Spinks C, Heath AL, Harvey LJ, Foxall R, Wimperis J, et al. Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment or pregnant women. Br J Nutr 2007; 97: 544–49.
• 23. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004; 113: 1271–76.
• 24. Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin- 6. Proc Natl Acad Sci USA 2005; 102: 1906–10.
• 25. Nicolas G, Chauvet C, Viatte L et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia and inflammation. J Clin Invest 2002; 110: 1037-44.
• 26. Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G. Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood 2006; 107: 4142-8.
• 27. Heinric PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990; 265: 621-36.
• 28. Kappa A, Piskorski A, Schopf E. Elevated levels of Interleukin 2 receptor in sera of patients with atopic dermatitis and psoriasis. Br J Dermatol 1988; 119: 707-10.
• 29. Evans CA, Jellis J, Hughes SP, Remick DG, Friedland JS. Tumour necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and theacute-phaseresponse in patients with bacterial and tuberculous osteomyelitis. J Infect Dis 1998; 177: 1582-87.
• 30. Evereklioglu C, Er H, Turkoz Y, Cekmen M. Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease. Mediators Inflamm 2002; 11: 87-93.
• 31. Hamzaoui K, Hamzaoui A, Guemira F, Bessioud M, Hamza M, Ayed K. Cytokineprofile in Behcet's disease patients. Scand J Rheumatol. 2002; 31: 205-10.
• 32. Etem A, Türkmen S, Etem E et al. Aktifya da inaktif Behçet hastalığı bulunan hastaların serum interlökin-6 ve adiponektin seviyeleri. Turkiye Klinikleri J Med Sci 2010; 30: 1837-44.
• 33. Soni A, Pepper GM, Wyrwinski PM et al. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. Am J Med 1995; 98: 266-71.
• 34. Kiraz S, Ertenli I, Arıcı M et al. Effects of colchicine on inflammatory cytokines and selectins in familial mediterranean fever. Clin Exp Rheumatol 1998; 16: 721-4.
• 35. Sun A, Wang YP, Chia JS, Liu BY, Chiang CP. Treatment with levamisole and colchicine can result in a significant reduction of IL-6, IL-8 or TNF-alpha level in patients with mucocutaneous type of Behcet's disease. J Oral Pathol Med 2009; 38: 401-5.