Buradasınız

Rekombinant Eritropoietin ile Tedavi Edilen Hemodiyaliz Hastalarında Antieritropoietin Antikorlar

Antierythropoietin Antibodies in Hemodialysis Patients Treated with Recombinant Erythropoietin

Journal Name:

Publication Year:

DOI: 
10.5262/tndt.2014.1002.08
Abstract (2. Language): 
OBJECTIVE: Erythropoietin resistance is a serious problem in patients treated with recombinant erythropoietin. Antierythropoietin antibodies are considered to be one of the causes of this resistance. MATERIAL and ME THODS: We investigated antierythropoietin antibodies in chronic hemodialysis patients and compared the results with healthy controls by means of establishing an ELISA method. A total of 121 chronic hemodialysis patients receiving recombinant erythropoietin were included in the study. The patients were subdivided according to the type of recombinant erythropoietin (erythropoietin-α or erythropoietin-β) they had been treated with in the last six months. RESUL TS: The absorbance values of patients were compared with the absorbance values of the control group by a specific and reproducible method. LOD (limit of detection) and LOQ (limit of quantitation) values were also calculated. The difference in the absorbance values between the therapy and control groups was statistically significant. CONCLU SION: Both erythropoietin-α and erythropoietin-β induce production of antibodies against erythropoietin. Anti rh-EPO antibodies may play a role in EPO resistance.
Abstract (Original Language): 
AMAÇ: Eritropoietin direnci rekombinant eritropoietin ile tedavi edilen hastalarda ciddi bir sorundur. Antieritropoietin antikorlar, bu direncin nedenlerinden biri olarak kabul edilir. GEREÇ ve YÖNTEMLE R: Kronik hemodiyaliz hastalarında ELISA yöntemi oluşturmak suretiyle antieritropoietin antikorları araştırıldı ve sonuçları sağlıklı kontrollerle karşılaştırıldı. Rekombinant eritropoetin alan 121 kronik hemodiyaliz hasta çalışmaya alındı. Hastalar bu son altı ay içinde tedavi edilmiş rekombinant eritropoietinin (eritropoietin - α ya da eritropoietin - β ) tipine göre ayrıldı . BUL GUL AR: Hastaların absorbans değerleri spesifik ve çoğaltılabilir bir yöntem ile kontrol grubunun absorbans değerleri ile karşılaştırıldı. LOD (saptanma limiti) ve LOQ (niceliklendirme sınır) değerleri de hesaplandı. Tedavi ve kontrol grubu arasında absorbans değerleri farkı istatistiksel olarak anlamlı idi. SONU Ç: Hem eritropoietin-α hem de eritropoietin-β eritropoietine karşı antikorların üretimini başlatabilir. Anti rh-EPO antikorları EPO direninde rol oynayabilir.
125
130

REFERENCES

References: 

1. Romanowski RR, Sytkowski AJ: The molecular structure of human
erythropoietin. Hematol Oncol Clin North Am 1994; 8: 885-894
2. Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui
LC, Rosenthal A: Large-scale sequencing of two regions in human
chromosome 7q22: Analysis of 650 kb of genomic sequence around
the EPO and CUTL1 loci reveals 17 genes. Genome Res 1998; 8:
1060-1073
3. Lappin TR, Winter PC, Elder GE, McHale CM, Hodges VH,
Bridges JM: Structure-function relationships of the erythropoietin
molecule. Ann N Y Acad Sci 1994; 718: 191-201
4. Yoshimura A, Arai K: Physician Education: The Erythropoietin
Receptor And Signal Transduction. Oncologist 1996; 1(5): 337-3395. Mohini R: Clinical efficacy of recombinant human erythropoietin in
hemodialysis patients. Semin Nephrol 1989; 9(1 Suppl 1):16-21
6. Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-
Dupont P, Michaud P, Papo T, Ugo V, Teyssandier I, Varet B,
Mayeux P: Pure red cell aplasia and anti erythropoietin antibodies
in patients treated with recombinant erythropoietin. N Engl J Med
2002; 346: 469-475
7. Imai N, Kawamura A, Higuchi M, Oh-eda M, Orita T, Kawaguchi
T, Ochi N: A Physicochemical and biological comparison
of recombinant human erythropoietin with human urinary
erythropoietin. J Biochem (Tokyo) 1990; 107: 352-359
8. Castelli G, Famularo A, Semino C, Machi AM, Ceci A, Cannella
G, Melioli G: Detection of anti-erythropoietin antibodies
in haemodialysis patients treated with recombinant humanerythropoietin.
Pharmacological Research 2000; 41: 313-318
9. Rossert J, Casadevall N, Eckardt KU: Anti-erythropoietin antibodies
and pure red cell aplasia. J Am Soc Nephrol 2004; 15(2): 398
10. Swanson SJ, Ferbas J, Mayeux P, Casadevall N: Evaluation of
methods to detect and characterize antibodies against recombinant
human erythropoietin. Nephron Clin Pract 2004; 96: 88-95
11. Long GL, Winefordner J: Limit of detection a closer look at the
IUPAC definition. Anal Chem 1983; 55(7): 712
12. Roskams J, Rodgers L: Lab Ref: A Handbook Of Recipes, Reagents
And Other Reference Tools For Use At The Bench, Cold Spring
Harbor, New York: Cold Spring Harbor Laboratory Press, 2002;1:20
13. Armbruster DA, Tillman MD, Hubbs LM: Limit of detection
(LQD)/limit of quantitation (LOQ): Comparison of the empirical
and the statistical methods exemplified with GC-MS assays of
abused drugs. Clin Chem 1994; 40(7 Pt 1): 1233-1238
14. KDIGO clinical practice guidelines for anemia in chronic kidney
disease. Kidney Int Suppl 2012; 2: 288
15. Pollock C, Johnson DW, Hörl WH, Rossert J, Casadevall N,
Schellekens H, Delage R, De Francisco A, Macdougall I, Thorpe
R, Toffelmire E: Pure red cell aplasia induced by erythropoiesisstimulating
agents. Clin J Am Soc Nephrol 2008; 3:193-19916. Casadevall N: Antibodies against rHuEPO: Native and recombinant.
Nephrol Dial Transplant 2002; 17S: 42-47
17. Janeway C, Travers P, Walport M, Shlomchick M: Immunobiology,
6th Edition. New York: Garland Publishing, 2005; 1: 21-22
18. Good RA, Park BH: Principles Of Modern İmmunobiology: Basic
And Clinical. Philadelphia: Lea&Febiger, 1974; 8: 82-83
19. Mytych DT, Barger TE, King C, Grauer S, Haldankar R, Hsu E, Wu
MM, Shiwalkar M, Sanchez S, Kuck A, Civoli F, Sun J, Swanson SJ:
Development and characterization of a human antibody reference
panel against erythropoietin suitable for the standardization of
ESA immunogenicity testing. J Immunol Methods 2012; 382(1-2):
129-141
20. Mytych DT, La S, Barger T, Ferbas J, Swanson SJ: The
development and validation of a sensitive, dual-flow cell, SPRbased
biosensor immunoassay for the detection, semi-quantitation,
and characterization of antibodies to darbepoetin alfa and epoetin
alfa in human serum. J Pharm Biomed Anal 2009; 49(2): 415-426
21. Kharagjitsingh AV, Korevaar JC, Vandenbroucke JP, Boeschoten
EW, Krediet RT, Daha MR, Dekker FW; NECOSAD Study Group:
Incidence of recombinant erythropoietin (EPO) hyporesponse,
EPO-associated antibodies, and pure red cell aplasia in dialysis
patients. Kidney Int 2005; 68: 1215-1222
22. Stoffel MP, Haverkamp H, Kromminga A, Lauterbach KW,
Baldamus CA: Prevalence of anti-erythropoietin antibodies in
hemodialysis patients without clinical signs o pure red cell aplasia.
Comparison between hypo- and normoresponsive patients treated
with epoetins for renal anemia. Nephron Clin Pract 2007; 105: c90-
98
23. Schett G, Firbas U, Füreder W, Hiesberger H, Winkler S, Wachauer
D, Köller M, Kapiotis S, Smolen J: Decreased serum erythropoietin
and its relation to anti erythropoietin antibodies in anemia of
sistemic lupus erythematosus. Rheumatology 2001; 40: 424-431
24. Elliott S, Chang D, Delorme E, Dunn C, Egrie J, Giffin J, Lorenzini
T, Talbot C, Hesterberg L: Isolation and characterization of
conformation sensitive antierythropoietin monoclonal antibodies:
Effects of disulfide bonds on human erythropoietin structure. Blood
1996; 87(7): 2714-2722

Thank you for copying data from http://www.arastirmax.com