Ali DELİBAŞ, Kenan BEK, Gülay DEMİRCİN, Ayşegül OKSAL, Özlem AYDOĞ, Mehmet BÜLBÜL, Ayşe ÖNER

Renal bcl-2/bax expression in childhood Henoch–Schönlein nephritis: prognostic importance?

Aim: To investigate the renal expression of apoptosis regulatory proteins b-cell lymphoma 2 (bcl-2) and bcl-2 associated X (bax) in children with Henoch–Schönlein nephritis (HSN) Materials and methods: Renal expression of antiapoptotic bcl-2 and proapoptotic bax proteins were studied immunohistochemically in 22 children with HSN. The kidneys of 5 children who died due to nonrenal reasons were used as the control. The patients were compared according to their renal histopathology and prognosis. Results: Nephrotic or nephrotic-nephritic renal involvement was the most common presentation. Histopathological findings were Class I in 1, Class II in 5, Class III in 10, Class IV in 4, and Class V in 2 patients. IgA staining was shown in all biopsies. Bcl-2 and bax proteins mainly showed tubular and crescentic expression. This was significantly different for bcl-2 in tubules and bax in distal tubules compared to the controls (P < 0.05). No significant difference between bax and bcl-2 expression was observed among patients. However the mean values of the bcl-2/bax ratio, that is, the balance between survival and apoptosis, were significantly higher in crescents of the severe histopathologic group and in distal tubules of the poor prognosis group (P < 0.05). Conclusion: A higher bcl-2/bax ratio, that is relative to the predominance of cell survival in distal tubules and crescents in HSN, seems to be a poor prognostic factor in children.

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1.Coppo R, Amore A. Henoch-Schönlein purpura. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric Nephrology, 6th ed. Berlin Heidelberg: Springer-Verlag; 2009. p.1111–26.
2.Allen RT, Cluck MW, Agrawal DK. Mechanisms controlling cellular suicide: role of Bcl-2 and caspases. Cell Mol Life Sci 1998; 54: 427–45.
3. Kelekar A, Thompson CB. Bcl-2 family proteins: the role of BH3 domain in apoptosis. Trends Cell Biol 1998; 8: 324–30.
4. Yoshimura A, Uda S, Inui K, Nemoto T, Sugenoya Y, Sharif S et al. Expression of bcl-2 and bax in glomerular disease. Nephrol Dial Transplant 1999; 14: 55–7.
5. Ozaltin F, Besbas N, Uckan D, Tuncer M, Topaloglu R, Ozen S et al. The role of apoptosis in childhood Henoch–Schonlein purpura. Clin Rheumatol 2003; 22: 265–7.
6. Mills JA, Michel BA, Bloch DA. Henoch-Schönlein purpura. Arthritis Rheumatism 1990; 33: 1114–21.
7. Charalambous GK, Gomatos IP, Konstadoulakis MM, Messaris EG, Manouras AJ, Apostolou AE et al. Protein expression of bax, bcl-2, and p53 in patients with non-Hodgkin’s gastric lymphoma: prognostic significance. World J Surg 2000; 24: 608–14.
8. Öner A, Tınaztepe K, Erdoğan Ö. The effect of triple therapy on rapidly progressive type of in Henoch-Schönlein nephritis. Pediatr Nephrol 1995; 9: 6 10. –
9. Chang WL, Yang YH, Wang LC, Lin YT, Chiang BL. Renal manifestations in Henoch–Schönlein purpura: a 10-year clinical study. Pediatr Nephrol 2005; 20: 1269–72.
10. Goldstein AR, White RHR. Long term follow-up of Henoch- Schönlein nephritis. Lancet 1992; 339: 280 2. –
11. Coppo R, Mazzuco G, Cagnoli L, Lupo A, Schena FP. For the Italian Group of Renal Immunopathology Collaborative Study on Henoch Schönlein Purpura. Long term prognosis of Henoch-Schönlein nephritis in adults and children. Nephrol Dial Transplant 1997; 12: 2277–83.
12. Lahita RG. Influence of age on Henoch-Schönlein purpura. Lancet 1997; 350: 1116–7.
13. Kaku Y, Nohara K, Honda S. Renal involvement in Henoch- Schönlein purpura: a multivariate analysis of prognostic factors. Kidney Int 1998; 53: 1755–9.
14. Woo D. Apoptosis and loss of renal tissue in polycystic kidney disease. N Engl J Med 1995; 333: 56–7.
15. Hammerman MR. Regulation of cell survival during renal development. Pediatr Nephrol 1998; 12: 596–602.
16. Aktuğ H, Çetintaş VB, Kosova B, Oltulu F, Demiray ŞB, Çavuşoğlu T et al. Dysregulation of nitric oxide synthase activity and Bcl-2 and caspase-3 gene expressions in renal tissue of streptozotocin-induced diabetic rats. Turk J Med Sci 2012; 42: 830–8.
17. Soto H, Mosquera J, Rodriguez-Iturbe B, La Roche CH, Pinto A. Apoptosis in proliferative glomerulonephritis: decreased apoptosis expression in lupus nephritis. Nephrol Dial Transplant 1997; 12: 273–80.
18. Takemura T, Murakami K, Miyazato H, Yagi K, Yoshioka K. Expression of Fas antigen and Bcl-2 in human glomerulonephritis. Kidney Int 1995; 48: 1886–92.
19. Uda S, Yoshimura A, Sugenoya Y, Inui K, Taira T, Ideura T. Mesangial proliferative nephritis in man is associated with increased expression of the cell survival factor, bcl-2. Am J Nephrol 1998; 18: 291–5.
20. Demircin G, Öner A, Ünver Y, Bülbül M, Erdoğan Ö. Erythrocyte superoxide dismutase activity and plasma malondialdehyde levels in children with Henoch- Schönlein purpura. Acta Pediatr 1998; 87: 848–52.
21. Mene P, Amore A. Apoptosis: potential role in renal diseases. Nephrol Dial Transplant 1998; 13: 1936–43.
22. Nakopoulou L, Stefananki K, Papadakis J, Boletis J, Zeis PM, Kostakis A et al. Expression of bcl-2 oncoprotein in various types of glomerulonephritis and renal allografts. Nephrol Dial Transplant 1996; 11: 997–1002.
23. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in progressive crescentic glomerulonephritis. Lab Invest 1996; 74: 941–51.
24. Yang B, Johnson TS, Thomas GL, Watson PF, Wagner B, Skill NJ et al. Expression of apoptosis-related genes and proteins in experimental chronic renal scarring. J Am Soc Nephrol 2001; 12: 275–88.
25. Yang B, Johnson TS, Thomas GL, Watson PF, Wagner B, Furness PN et al. A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis. Kidney Int 2002; 62: 1301–13.