ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.

We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L). Eighteen patients with bronchial asthma (BA), and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden). Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03), , and in cases of chronic GvHD (p < 0.03), and in a sub-group with lymphoproliferative disorders (р = 0.007) as compared to the group of non-hematological diseases.

Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03), as well in GvHD compared with lymphoproliferative disorders (р < 0.05).

A direct correlation was found between serum ECP levels and absolute eosinophil counts in peripheral blood for general hematological group (r = 0.51; р = 0.000001), and for a group of patients with lymphoproliferative diseases (r = 0.9; р = 0.000001). Hence, a quantitative determination of soluble eosinophylic proteins and mast cell-specific enzymes in blood serum are useful for diagnostics and monitoring of various hypereosinophilic conditions in oncohematological disorders. (Med. Immunol., vol. 10, N 4-5, pp 361-370).

1. Боровиков В. STATISTICA. Искусство анализа данных на компьютере: Для профессионалов. – 2-е изд. – СПб.: Питер, 2003. – 688 с.

2. Гланц С. Медико-биологическая статистика: Пер. с англ. – М.: Практика, 1998. – 459 с.

3. Клиническая онкогематология: Руководство для врачей / Под ред. М.А. Волковой. – М.: Медицина, 2001. – 576 с.: ил.

4. Комарова Л.С., Зуева Е.Е., Михайлова Н.Б., Буравцова Н.А., Нестерович И.И., Афанасьев Б.В., Тотолян А.А. Опыт определения триптазы и эозинофильного катионного белка у пациентов с эозинофилией различного происхождения // Мед. иммунология. – 2004. – Т. 6, № 3-5. – С. 353.

5. Комарова Л.С., Зуева Е.Е., Нестерович И.И., Михайлова Н.Б., Афанасьев Б.В., Тотолян А.А. Роль внутриклеточных белков эозинофилов и тучных клеток в развитии эозинофилии при различных заболеваниях // Рос. иммунол. журн. – 2007. – Т. 1, № 10. – С. 27-33.

6. Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. – М.: МедиаСфера, 2003. – 312 с.

7. Руководство по гематологии: в 3 т. Т. 1. / Под ред. А.И. Воробьева. – 3-е изд., перераб. и допол. – М.: Ньюдиамед, 2002. – 280 с.

8. Фрейдлин И.С., Тотолян А.А. Иммунопатологические механизмы воспаления бронхов и легких // Механизмы воспаления бронхов и легких и противовоспалительная терапия. – СПб., 1998. – 194-298 с.

9. Фрейдлин И.С., Тотолян А.А. Клетки иммунной системы. Т. 3-5. – СПб., 2000. – С. 204.

10. Aisa Y., Mori T., Nakazato T., Shimizu T., Yamazaki R., Ikeda Y., Okamoto S. Blood eosinophilia as a marker of favorable outcome after allogeneic stem cell transplantation // Transpl. Int. – 2007. – Vol. 20, Iss. 9. – P. 761-770.

11. Andreas R., Grimwade D., Cross N.C.P. Diagnostic and therapeutic management of eosinophilia-associated chronic myeloproliferative disorders // Haematologica/Hematol. J. – 2007. – Vol. 92, N 9. – P. 1153-1158.

12. Ayalew Tefferi A., Patnaik M.M., Pardanani A. Eosinophilia: secondary, clonal and idiopathic // Br. J. Haematol. – 2006. – Vol. 133. – P. 468-492.

13. Brito-Babapulle F. The eosonophilias, including the idiopathic hypereosinophilic syndrome. Review // Br. J. Haematol. – 2003. – Vol. 121. – P. 203-223.

14. Fletchera S., Bain B. Diagnosis and treatment of hypereosinophilic syndromes // Curr. Opin. Hematol. – 2006. – P. 1-6.

15. Fletchera S., Bain B. Eosinophilic leukaemia // Br. Med. Bull. – 2007. – P. 1-13.

16. Gotlib J., Cross N.C.P., Gilliland D.G. Eosinophilic disorders: molecular pathogenesis, new classification, and modern therapy // Best Practice & Research Clinical Haematology. – 2006. – Vol. 19, N 3. – P. 535-569.

17. Klion A.D., Noel P., Akin C., Law M.A., Gilliland D.G., Cools J., Metcalfe D.D., Nutman T.B. Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness // Blood. – 2003. – Vol. 101. – P. 4660-4666.

18. Lotfi R., Lee J.J., Lotze M.T. Eosinophilic granulocytes and damage-associated molecular pattern molecules (DAMPs): role in the inflammatory response within tumors // J. Immunother. – 2007. – Vol. 30, N 1. – P. 16-28.

19. Mingomataj E.C. Eosinophil-induced prognosis improvement of solid tumors could be enabled by their vesicle-mediated barrier permeability induction // Med. Hypotheses. – 2007. – P. 1-3.

20. Pardanani A., Reeder T., Li C-Y., Tefferi A. Eosinophils are derived from the neoplastic clone in patients with systemic mastocytosis and eosinophilia // Leuk. Res. – 2003. – Vol. 23. – P. 883-885.

21. Robinson D.S., Kay A.B., Wardlaw A.J. Eosino phils // Clin. Allergy Immunol. – 2002. – Vol. 16. – P. 43-75.

22. Sade K., Mysels A., Levo Y., Kivity S. Eosinophilia: A study of 100 hospitalized patients // Eur. J. Intern. Med. – 2007. – Vol. 18. – P. 196-201.

23. Schwartz R.S. The hypereosinophilic syndrome and the biology of cancer // N. Engl. J. Med. – 2003. – Vol. 348, N 13. – P. 1199-1201.

24. Simon D., Simon H-U. Eosinophilic disorders // J. Allergy Clin. Immunol. – 2007. – P. 1291-1300.

25. Sperr W.R., Hauswirth A.W., Valent P. Tryptase a novel biochemical marker of acute myeloid leukemia // Leuk. Lymphoma. – 2002. – Vol. 43, N 12. – P. 2257-2261.

26. Sperr W.R., Jordan J.H., Baghestanian M., Kiener H.P., Samorapoompichit P., Semper H., Hauswirth A., Schernthaner G.H., Chott A., Natter S., Kraft D., Valenta R., Schwartz L.B., Geissler K., Lechner K., Valent P. Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia // Blood. – 2001. – Vol. 98, N 7. – P. 2200-2209.

27. Sperr W.R., Mitterbauer M., Mitterbauer G., Kundi M., Lechner U.K., Valent P. Quantitation of minimal residual disease in acute myeloid leukemia by tryptase monitoring identifies a group of patients with a high risk of relapse // Clin Cancer Res. – 2005. – Vol. 11, N 18. – P. 6536-6543.

28. Valent P., Samorapoompichit P., Sperr W.R., Horny H.P., Lechner K. Myelomastocytic leukemia: myeloid neoplasm characterized by partial differentiation of mast cell-lineage cells // Hematol. J. – 2002. – Vol. 3, N 2. – P. 90-94.

29. Wilkinson K., Velloso E.R.P., Lopes L.F., Lee C., Aster J.C., Shipp M.A., Aguiar R.C.T. Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to Imatinib // Blood. – 2003. – Vol. 102. – P. 4187-4190.