Fankoni anemili hastaların mitojenlere, bakteriyel ve viral antijenlere karşı in vitro lenfoproliferatif yanıtları

Year 2008, Volume: 5 Issue: 2, 19 - 23, 01.08.2008

Faruk Süzergöz Ali O Gürol Fatih M Evcimik Nevin Yalman

Abstract

Fankoni anemili hastaların enfeksiyonlara karşı artmış hassasiyeti, hastaların mitojenlere, bakteriyel ve viral antijenlere karşı immün cevap yetenekleri in vitro ortamda belirlenmek suretiyle incelenmiştir. Periferik kan mononükleer hücreleri PBMC 11 Fankoni anemili hasta ve 11 sağlıklı kontrol bireyinden alınmıştır. Her bir örnekten 105 hücre alınarak MTT yöntemiyle, 20 µg/ml fitohemaglutinin, PHA , 10 µg/ml pokeweed mitojen PWM , 6 µg/ml Tetanoz toksoidi TT , 10 µg/ml saflaştırılmış mycobacterium proteini PPD and 1.25 µg/ml citomegalovirus CMV antijeni ile test edilmiştir. PHA, PWM, TT ve PPD’ ye karşı lenfoproliferatif yanıt kontrol grubuna göre Fankoni anemili hastalarda anlamlı şekilde düşük bulunmuştur. CMV seropozitif hastalarda ise CMV antijenine karşı lenfoproliferatif yanıt CMV seronegatif hastalardan daha yüksek bulunmuştur. Sonuç olarak, Fankoni anemili hastalarda mitojenlere, bakteriyel ve viral antijenlere karşı düşük lenfoproliferatif yanıtın infeksiyonlara yatkınlığın bir işareti olduğunu fakat CMV seropozitif hastalarda görüldüğü gibi antijenle temas durumunda hücrelerin immunopotent hale dönüşebildiğini söyleyebiliriz

Keywords

Fanconi anemisi, lenfoproliferasyon, mitojen, citomegalovirus

Lymphoproliferative response of Fanconi anemia patients to mitogens, bacterial and viral antigens in vitro

Abstract

Increased susceptibility to infections in Fanconi anemia FA have been investigated by determining immune response capability of the patients against to mitogenic, bacterial and viral antigens in vitro. Peripheral blood mononuclear cells PBMC were obtained from 11 FA patients and 11 healthy control individuals. 105 cells from each sample were assessed by using colorimetric MTT assay including 20 µg/ml pytoheamagglutinine PHA , 10 µg/ml pokeweed mitogen PWM , 6 µg/ml Tetanus toxoid TT , 10 µg/ml purified protein derivative of mycobacterium PPD and 1.25 µg/ml cytomegalovirus CMV antigen. Lymphoproliferative response to PHA, PWM, TT and PPD were found significantly lower in FA patients than control group. Lymphoproliferation to CMV antigen was significantly higher in CMV seropositive than seronegative FA patients. To conclude, the lower lymphoproliferative response capability to mitogens and bacterial antigens in FA patients implied susceptibility to infections, but, it is likely in CMV seropositive FA patients, the cells encountering antigens could become immunopotent

Keywords

Fanconi anemia, lymphoproliferation, mitogen, cytomegalovirus

References

• D’Andrea AD, Dahl N, Guinan EC, Shimamura A. Marrow Failure. Hematology (Am Soc Hematol Educ Program) 2002; 58-72. 2.
• Tischkowitz M, Dokal I. Fanconi anaemia and leukaemia – clinical and molecular aspects B J Haematol 2004; 126: 176–91. 3.
• Rosselli F, Sanceau J, Wietzerbin J, Abnormal Moustacchi
• production: a novel feature of the genetic disease Fanconi anemia. I. Involvement of interleukin-6. Hum Genet 1992; 89: 42-8. 4.
• lymphokine Stark R, Thierry D, Richard P, Gluckman E. Long-term bone marrow culture in Fanconi’s anaemia. B J Haematol 1993; 83: 554–9. 5.
• Lensch M.W., Rathbun R.K., Olson S.B., Jones G.R., Bagby G.C. (1999) Selective pressure as an essential force in molecular volution of myeloid leukemic clones: a view from the window of Fanconi anemia. Leukemia 13: 1784–9. 6.
• Stark R., Andre C., Thierry D., Cherel M., Galibert F., Gluckman E. The expression of cytokine and cytokine receptor genes in long- term bone marrow culture in congenital and acquired bone marrow hypoplasias. B J Haematol 1993; 83: 560-6. 7.
• Rosselli F, Sanceau J, Gluckman E, Wietzerbin J, Moustacchi E. Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia: II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha. Blood 1994; 83: 1216–25. 8.
• Schultz JC, Shahidi NT. Tumor necrosis factor-alpha overproduction in Fanconi’s anemia. Am J Hematol 1993; 42: 196–201. 9. de Cremoux P, Gluckman
• E, Podgorniak MP., Menier C, Thierry D, Calvo F, Socie G. Decreased IL-1 beta and TNF alpha secretion in long-term bone marrow culture supernatant from Fanconi's anaemia patients. Eur J Haematol 1996; 57: 202-7. 10.
• Ozkan B. Recurrent aphthous ulcers in Fanconi's anaemia: a case report. Int J Paediatr Dent 2004; 14: 214-7. 11.
• Kulekci G, Anak S. The effect of bone marrow transplantation on systemic and oral health in Fanconi's aplastic anemia. Clin Pediatr Dent 2001; 25: 329-32 12.
• Contreras A, Slots J. Aggressive periodontitis associated with Fanconi's anemia. A case report. J Periodontol 2001; 72: 1601-6. 13.
• MJ. Vibrio cholerae (non-O1, non-O139) sepsis in a child with Fanconi anemia. Diagn Microbiol Infect Dis 2004; 50: 287-9. 14.
• S. Differential diagnosis of Fanconi anemia by nitrogen mustard and diepoxybutane. Ann Hematol 2003; 82: 223-7. 15.
• Lazzarotto T, Landini MP, Bruggeman CA. IgM antibody detection of ppUL80A and ppUL32 by immunoblotting: an early parameter for recurrent cytomegalovirus infection in renal transplant recipients. J Med Virol 1996; 48: 289- 94. 16.
• Characterization of mouse cells releasing or responding to mitogenic factor induced by phytomitogens in vitro. J Immunol 1975; 114: 1631-7 17.
• assessment of lectin-mediated mitogenesis. Mol Biotechnol 1999; 11: 55–65. 18. HM.
• lymphocytes in vitro. I. Characterization of the lymphocyte response to a T cell-independent B cell mitogen. J Immunol 1980; 125: 820-6. 19.
• Goodwin JS. Specific humoral immunity in the elderly: in vivo and in vitro response to vaccination. J Gerontol 1993; 48: 231-6. 20.
• Goldman J, Lombardi G, Melo JV, Dazzi F. Imatinib inhibits the activation and proliferation of normal T lymphocytes in-vitro. Leukemia 2004; 18: 1332-9. 21.
• Grangeot-Keros L. CMV-IGG avidity and CMV-IGM immunocompromised and immunocompetent patients. Pathol Biol 1996; 44: 405-10. 22.
• RA, Galasso GJ, Griffiths PD, Jabs DA, Katlama C, Spector SA. Whitley RJ. Summary of the International Consensus Symposium on Advances in the Diagnosis,Treatment and Prophylaxis and Cytomegalovirus Infection. Antiviral Res 1996; 32: 119-40. 23.
• Blanchet O, Kouyoumdjian S, Lunel F. Novel DNA assay for cytomegalovirus detection: comparison with conventional culture and pp65 antigenemia assay. J Clin Microbiol 1996; 34: 3097-100.