Interleukin 10 and TGF-Beta gene polymorphisms can effect granulomatous formatıonın chronic granulomatous disease

Kronik granülomatöz hastalık, nadir görülen fatal seyirli ve kalıtsal geçiş gösteren bir immün yetmezlik hastalığıdır. Hastalarda sıklıkla tekrarlayan bakteriyel ve fungal enfeksiyonlar, anormal inflamatuvar cevap gelişimi ve granülom oluşumları gözlenmektedir. Bu hastalarda fonksiyonel bozukluklara da neden olabilen granülom oluşumlarının nedeni tam olarak açıklanamamıştır Amaç: Bu çalışma kronik granülomatöz hastalık tanısı almış olan hastalarda bakteriyal ve fungal patojenlerin neden olduğu inflamasyon ve granülom formasyonu oluşumu ile sitokin gen polimorfizmleri arasında bir ilişki olup olmadığını saptamak amacıyla yapılmıştır. Hasta ve Metod: Kronik granülomatöz hastalık tanısı almış 4 hastanın ve 60 sağlıklı gönüllü donörün kanlarından elde edilen DNA örneklerinden, önceden seçilmiş olan sitokin gen polimorfizmleri (TNF-α, TGF-β, IL-10, IL-6, and IFN-γ) PCR SSP yöntemi ile çalışılmıştır. Sonuç: Hasta grubunda interlökin-10 -1082 ACC/ATA polimorfizm varlığında anlamlı fark saptanmıştır. Yorum: IL-10 ACC/ATA polimorfizm varlığının granulom formasyonu ile ilişkili olabileceğini göstermektedir.

İnterlökin 10 ve TGF-Beta gen polimorfizmleri kronik granülomatoz hastalıkta granülom formasyonu oluşumunda etkili olabilir mi?

Chronic granulomatous disease (CGD) is a rare and fatal inherited immunodeficiency syndrome. Recurrent bacterial and fungal infections, abnormal inflammatory responses and granuloma formation are common. Purpose: Patients with CGD are susceptible to bacterial and fungal pathogens, with associated dysregulated inflammation and widespread granuloma formation. The objective of this study was to evaluate the clinical presentation, granuloma formation and association with cytokine gene polymorphisms. Patients and Methods: Four patients with CGD and 60 healthy controls were enrolled in this study. All genotyping (TNF-α, TGF-β, IL-10, IL-6, and IFN-γ) studies were performed using sequence-specific primers (PCRSSP). Results: Frequencies of IL-10 (-1082, -819, -592) ACC/ATA polymorphism were significantly greater in the patients with CGD. Conclusion: The results suggest that the IL-10 ACC/ATA polymorphism is associated with granuloma formation.

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1. Quie PG. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest 1967; 46: 668-679.
2. Segal BH, Leto TL, Gallin JI, Malech HL, Holand SM. Genetic, biochemical and clinical features of chronic granulomatous disease. Medicine. 2000; 79: 170-200.
3. Chin TW, Stiehm ER, Falloon J, Gallin JI. Corticosteroids in treatment of obstructive lesions of chronic granulomatous disease. J Pediatr.1987; 111: 349-352.
4. Danziger RN, Goren AT, Becker J, Greene JM, Douglas SD. Outpatient management with oral corticosteroid therapy for obstructive conditions in chronic granulomatous disease. J Pediatr. 1993; 122: 303-305.
5. Mouy R, Fischer A, Vilmer E, Seger R, Griscelli C. Incidence, severity and prevention of infections in chronic granulomatous disease. J Pediatr 1989; 114: 555-560.
6. Warlé MC, Farhan A, Metselaar HJ, Hop WCJ, Perrey C, Zondervan PE, Kap M, Kwekkeboom J, Ijzermans JNM, Tilanus HW, Pravica V, Hutchinson IV, Bouma GJ. Are cytokine gene polymorphisms related to in vitro cytokine production profiles? Liver Transpl. 2003; 9: 170-181.
7. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the IL10 gene promoter. Eur J Immunogenet. 1997; 24: 1-8.
8. Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. Novel polymorphisms in the interleukin-6 gene: Their effect on IL-6 transcription, plasma IL-6 levels and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998; 102: 1369-1376.
9. Basturk B, Yavascaoglu I, Vuruskan H, Goral G, Oktay B, Oral HB. Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma. Cytokine 2005; 7: 41-45.
10. Karasu Z, Ulukaya S, Ayanoglu HO, Basturk B, Ulukaya E, Akyildiz M, Tokat Y. Cytokine gene polymorphism and early graft rejection in liver transplant recipients. Transplantation Proceedings 2005; 36: 2791-2795.
11. Abbas A, Lichtman HA, Pobers J. Cellular and molecular immunology, fourth edition, New York, W.B. Saunders Company, 2000. 12. Schappi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch Dis Child. 2001; 84: 147-151.
13. Lindahl JA, Williams FH, Newman SL. Small bowel obstruction in chronic granulomatous disease. J Pediartic Gastroenterol Nutr. 1984; 3: 637-40.
14. Nadler R, Luo Y, Zhao W, et al. Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guerin (BCG) mediated antitumour activity. Clinical Experimental Immunology 2003; 131: 206-216.
15. Kube D, Rieth H, Eskdale J, Kremsner PG, Gallagher G. Structural characterisation of the distal 5´ flanking region of the human interleukin- 10 gene. Genes Immunity 2001; 2: 181.