Turkiye Klinikleri Journal of Internal Medicine

.: REVIEW
Böbrek Nakillerinde Kompleman Sistemine Bakış
Overview of Complement System in Renal Transplantation
Tülay KILIÇASLAN AYNAa,b, İbrahim PİRİMa,b
aİzmir Kâtip Çelebi Üniversitesi Tıp Fakültesi, Tıbbi Biyoloji ABD, İzmir, TÜRKİYE
bSağlık Bilimleri Üniversitesi Tepecik Eğitim ve Araştırma Hastanesi, Doku Tipleme Laboratuvarı, İzmir, TÜRKİYE
Turkiye Klinikleri J Intern Med. 2020;5(3):123-36
doi: 10.5336/intermed.2019-72752
Article Language: TR
Full Text
ÖZET
 İmmün sistem, 3 ana kısımdan oluşmaktadır. Bunlar; immün sistem organları, immünositler adı da verilen immün sistem hücreleri ve immün moleküllerdir. Kompleman, çok sayıda protein içeren, doğal ve edinsel immün sistemin temel moleküllerindendir. Vücuttaki kompleman proteinlerinin oranı ve farklı kompleman proteinleri arasındaki denge, hastalıklarla yakından ilişkilidir. Kompleman sistemi, 3 farklı yolla aktifleşerek yabancı olan moleküllerden konağı korur. Farklı kompleman proteinleri ile başlayan aktivasyon süreci ortak bir mekanizma ile sonlanır. Böbrek nakli de aslında immün sistemin bir sınavıdır. Canlı veya kadavra vericiden (donör) alınan böbrek, hastaya yabancıdır ve nakil hastadaki immün sistemi harekete geçirir. Kompleman proteinleri de doğal olarak bu sürece katılır. Bu derlemede, naklin 2 tarafı olan hasta ve donörün, kompleman sistemine olan katkısı değerlendirilmiştir. Hastada, böbrek yetersizliğine gidişi tetikleyen kompleman proteinlerindeki anormal durumlar, hastalıktan kaynaklanan inflamasyon ve son dönem böbrek yetersizliği olan hastalardaki diyalizin, kompleman proteinlerini etkilemesi muhtemeldir. Özellikle kadavradan yapılan nakillerde, yoğun bakım ünitelerindeki donörlerden kaynaklı veya iskemi süreleri ile kompleman sisteminin aktivasyonu oluşur. Bu donörlerdeki, hemodinamik dengesizlik, hormon düzensizliği ve inflamatuar reaksiyonlar önemli fizyolojik değişikliklere neden olur. Sonuçta olarak, hücre fenotiplerinin değişimi, kemokin ve sitokin havuzlarındaki farklılıklar, kompleman aktivasyonuyla sonuçlanabilir. Farklı yolların aktivasyonu ve bu yollar arasındaki sinerji, immün reaksiyonu güçlendirir. Nakil öncesinde ve sonrasında immün sistem aktivasyonunun, kompleman penceresinden de değerlendirilmesi organ nakli kliniklerine katkı sağlayacaktır.

Anahtar Kelimeler: Böbrek transplantasyonu; diyaliz; kompleman
ABSTRACT
 The immune system consists of three main parts. These are organs of the immune system, cells of the immune system, also called immunocytes, and immune molecules. Complement is one of the basic molecules of the natural and acquired immune system that contains a large number of proteins. The proportion of complement proteins in the body and the balance between different complement proteins are closely related to diseases. The complement system is activated in three different ways to protect the host from foreign molecules. The activation process starts with different complement proteins and ends with a common mechanism. Renal transplantation is also the factor that activates the immune system. The kidney from living or cadaver donor is foreign to the patient and the transplant activates the immune system. Complement proteins are also naturally involved in this process. In this review, the contribution to the complement system of the patient and donor, who are on both sides of the transplant was evaluated. Abnormal conditions in the complement proteins that triggering the progression to renal failure in the patient, inflammation caused the disease, and dialysis in patients with endstage renal failure are likely to affect complement proteins. Especially in cadaver transplants, activation of the complement system occurs due to donor in intensive care units or ischemia times. Hemodynamic imbalance, hormone disorder and inflammatory reactions in these donors cause important physiological changes. As a result, changes in cell phenotypes, differences in chemokine and cytokine pools may result in complement activation. The evaluation of immune system activation before and after transplantation from the complement window will contribute to organ transplantation clinics.

Keywords: Kidney transplantation; dialysis; complement
REFERENCES:
  1. Nesargikar PN, Spiller B, Chavez R. The complement system: history, pathways, cascade and inhibitors. Eur J Microbiol Immunol (Bp). 2012;2(2):103-11.[PubMed] 
  2. Reis ES, DeAngelis RA, Chen H, Resuello RRG, Ricklin D, Lambris JD. Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology. 2015;220(4):476-82.[Crossref] [PubMed] 
  3. Nonaka M. Evolution of the complement system. Subcell Biochem. 2014;80:31-43.[Crossref] [PubMed] 
  4. Barnum SR. Complement: A primer for the coming therapeutic revolution. Pharmacol. Ther. 2017;172:63-72.[Crossref] [PubMed] 
  5. Tichaczek-Goska D. Deficiencies and excessive human complement system activation in disorders of multifarious etiology. Adv Clin Exp Med. 2012;21(1):105-14.[PubMed] 
  6. Michielsen LA, van Zuilen AD, Muskens IS, Verhaar MC, Otten HG. Complement polymorphisms in kidney transplantation: critical in graft rejection? Am J Transplant. 2017;17(8):2000-7.[Crossref] [PubMed] 
  7. Biglarnia AR, Huber-Lang M, Mohlin C, Ekdahl KN, Nilsson B. The multifaced role of complement in kidney transplantation. Nat Rev Nephrol. 2018;14(12):767-81.[Crossref] [PubMed] 
  8. Abbas A, Lichtman A, Pillai S. Effector Mechanisms of Humoral Immunity, Cellular and Mo­lecular Immunology. 7th ed. Philadelphia: El­sevier; 2011. p.269-92. https://www.elsevier.com/books/cellular-and-molecular-immunology/abbas/978-1-4377-1528-6
  9. Khan MA, Shamma T. Complement factor and T-cell interaction during alloimmune inflamation in transplantation. J Leukoc Biol. 2019;105(4):681-94.[Crossref] [PubMed] 
  10. Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part ý - molecular mechanisms of activation and regulation. Front Immunol. 2015;6;262:1.[Crossref] 
  11. de Taeye SW, Rispens T, Vidarsson G. The ligands for human IgG and their effector functions. Antibodies (Basel). 2019;25;8(2):30.[Crossref] [PubMed] [PMC] 
  12. Sharp TH, Boyle AL, Diebolder CA, Kros A, Koster AJ, Gros P, et al. Insights into IgM- madiated complement activation based on in situ structures of IgM-C1-C4b. Proc Natl Acad Sci U S A. 2019;116(24):11900-05.[Crossref] 
  13. Petru?ić V, Živković I, Stojanović M, Stojićević I, Marinković E, Dimitrijević L. Hexameric immunoglobulin M in humans: desired or unwanted? Med Hypotheses. 2011;77(6):959-61.[Crossref] [PubMed] 
  14. Stowell SR, Winkler AM, Maier CL, Arthur CM, Smith NH, Girard-Pierce KR, et al. Initiation and regulation of complement during hemolytic transfusion reactions. Clin Dev Immunol. 2012;2012:307093.[Crossref] [PubMed] [PMC] 
  15. Dekkers G, Treffers L, Plomp R, Bentlage AEH, de Boer M, Koeleman CAM, et al. Decoding the human immunoglobulin g-glycan repertoire reveals a spectrum of fc-receptor- and complement-mediated-effector activities. Front Immunol. 2017;2;8:877. eCollection 2017.[Crossref] [PubMed] [PMC] 
  16. Subedi GP, Hanson QM, Barb AW. Restricted motion of the conserved immunoglobulin G1 N-glycan is essential for efficient Fc?RIIIa binding. Structure. 2014;7;22(10):1478-88.[Crossref] [PubMed] [PMC] 
  17. Beltrame MH, Catarino SJ, Goeldner I, Boldt ABW, de Messias-Reason IJ. The lectin pathway of complement and rheumatic heart disease. Front Pediatr. 2015;21;2:148.[Crossref] [PubMed] [PMC] 
  18. Poppelaars F, Faria B, Gaya da Costa M, Franssen CFM, van Son WJ, Berger SP, et al. The complement system in dialysis: a forgotten story? Front Immunol. 2018;25;9:71.[Crossref] [PubMed] [PMC] 
  19. Kerr PG, Huang L. Review: membranes for haemodialysis. Nephrology (Carlton). 2010;15(4):381-5.[Crossref] [PubMed] 
  20. Craddock PR, Fehr J, Brigham KL, Kronenberg RS, Jacob HS. Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med. 1977;7;296(14):769-74.[Crossref] [PubMed] 
  21. Hempel JC, Poppelaars F, Gaya da Costa M, Franssen CFM, de Vlaam TPG, Daha MR, et al. Distinct in vitro complement activation by various intravenous iron preparations. Am J Nephrol. 2017;45(1):49-59.[Crossref] [PubMed] 
  22. Damman J, Seelen MA, Moers C, Daha MR, Rahmel A, Leuvenink HG, et al. Systemic complement activation in deceased donors is associated with acute rejection after renal transplantation in the recipient. Transplantation. 2011;27;92(2):163-9.[Crossref] [PubMed] 
  23. Sim E, Sim RB. Enzymic assay of C3b receptor on intact cells and solubilized cells. Biochem J. 1983;15;210(2):567-76.[Crossref] [PubMed] [PMC] 
  24. Denk S, Neher MD, Messerer DAC, Wiegner R, Nilsson B, Rittirsch D, et al. Complement C5a functions as a master switch for the ph balance in neutrophils exerting fundamental immunometabolic effects. J Immunol. 2017;15;198(12):4846-54.[Crossref] [PubMed] 
  25. Farrar CA, Tran D, Li K, Wu W, Peng Q, Schwaeble W, et al. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury. J Clin Invest. 2016;2;126(5):1911-25.[Crossref] [PubMed] [PMC] 
  26. Kolářová H, Ambrůzová B, Svihálková ?indlerová L, Klinke A, Kubala L. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm. 2014;2014:694312.[Crossref] [PubMed] [PMC] 
  27. Castellano G, Intini A, Stasi A, Divella C, Gigante M, Pontrelli P, et al. Complement modulation of anti-aging factor klotho in ischemia/reperfusion injury and delayed graft function. Am J Transplant. 2016;16(1):325-33.[Crossref] [PubMed] 
  28. Delpech PO, Thuillier R, SaintYves T, Danion J, Le Pape S, van Amersfoort ES, et al. Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation. J Transl Med. 2016;23;14(1):277.[Crossref] [PubMed] [PMC] 
  29. Nauser CL, Farrar CA, Sacks SH. Complement recognition pathways in renal transplantation. J Am Soc Nephrol. 2017;28(9):2571-8.[Crossref] [PubMed] [PMC] 
  30. Zhang R. Donor-specific antibodies in kidney transplant recipients. Clin J Am Soc Nephrol. 2018;6;13(1):182-92.[Crossref] [PubMed] [PMC] 
  31. Kılıçaslan Ayna T, Pirim İ. [Rejection mechanisms and bioindicators in kidney transplantation]. Turkiye Klinikleri J Intern Med. 2019;4(1):13-24.[Crossref] 
  32. Hamer R, Molostvov G, Lowe D, Satchell S, Mathieson P, Ilyas R, et al. Human leukocyte antigen- specific antibodies and gamma- interferon stimulate human microvascular and glomerular endothelial cells to produce complement factor C4. Transplantation. 2012;93(9):867-73.[Crossref] [PubMed] 
  33. Lee H, Han E, Choi AR, Ban TH, Chung BH, Yang CW, et al. Clinical impact of complement (C1q, C3d) binding De Novo donor-specific HLA antibody in kidney transplant recipients. PLoS One. 2018;14;13(11):e0207434.[Crossref] [PubMed] [PMC] 
  34. Delanghe JR, Speeckaert R, Speeckaert MM. Complement C3 and its polymorphism: biological and clinical consequences. Pathology. 2014;46(1):1-10.[Crossref] [PubMed] 
  35. Grafals M, Thurman JM. The role of complement in organ transplantation. Front Immunol. 2019;4;10:2380.[Crossref] [PubMed] [PMC] 
  36. Mohebnasab M, Eriksson O, Persson B, Sandholm K, Mohlin C, Huber-Lang M, et al. Current and future approaches for monitoring responses to anti-complement therapeutics. Front Immunol. 2019;8;10:2539.[Crossref] [PubMed] [PMC] 
  37. Lewis AG, Köhl G, Ma Q, Devarajan P, Köhl J. Pharmacological targeting of C5a receptors during organ preservation improves kidney graft survival. Clin Exp Immunol. 2008;153(1):117-26.[Crossref] [PubMed] [PMC] 
  38. Rich MC, Keene CN, Neher MD, Johnson K, Yu ZX, Ganivet A, et al. Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains. Neurosci Lett. 2016;23;617:188-94.[Crossref] [PubMed] 
  39. Ruseva MM, Ramaglia V, Morgan BP, Harris CL. An anticomplement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice. Proc Natl Acad Sci USA. 2015;17;112(46):14319-24.[Crossref] [PubMed] 
  40. Stegall MD, Diwan T, Raghavaiah S, Cornell LD, Burns J, Dean PG, et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011;11(11):2405-13.[Crossref] [PubMed] 
  41. Sicard A, Ducreux S, Rabeyrin M, Couzi L, McGregor B, Badet L, et al. Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. J Am Soc Nephrol. 2015;26(2):457-67.[Crossref] [PubMed] [PMC] 
  42. Tillou X, Poirier N, Le Bas-Bernardet S, Hervouet J, Minault D, Renaudin K, et al. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons. Kidney Int. 2010;78(2):152-9.[Crossref] [PubMed] 
  43. Kirschfink M. C1-inhibitor and transplantation. Immunobiology. 2002;205(4-5):534-41.[Crossref] [PubMed] 
  44. Viglietti D, Gosset C, Loupy A, Deville L, Verine J, Zeev A, et al. C1 inhibitor in acute antibody-mediated rejection nonresponsive to conventional therapy in kidney transplant recipients: a pilot study. Am J Transplant. 2016;16(5):1596-603.[Crossref] [PubMed] 
  45. Montgomery RA, Orandi BJ, Racusen L, Jackson AM, Garonzik-Wang JM, Shah T, et al. Plasma-derived C1 esterase inhibitor for acute antibody-mediated rejection following kidney transplantation: results of a randomized double-blind placebo-controlled pilot study. Am J Transplant. 2016;16(12):3468-78.[Crossref] [PubMed] 
  46. Halloran PF, Reeve JP, Pereira AB, Hidalgo LG, Famulski KS. Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: new insights from the Genome Canada studies of kidney transplant biopsies. Kidney Int. 2014;85(2):258-64.[Crossref] [PubMed] 
  47. Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018;14(1):26-47.[Crossref] [PubMed] [PMC] 
  48. Mastellos DC, Yancopoulou D, Kokkinos P, Huber-Lang M, Hajishengallis G, Biglarnia AR, et al. Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. Eur J Clin Invest. 2015;45(4):423-40.[Crossref] [PubMed] [PMC] 
  49. Vogel CW, Fritzinger DC. Cobra venom factor: structure, function, and humanization for therapeutic complement depletion. Toxicon. 2010;15;56(7):1198-222.[Crossref] [PubMed] 
  50. Heeger PS, Kemper C. Novel roles of complement in T effector cell regulation. Immunobiology. 2012;217(2):216-24.[Crossref] [PubMed] 

.: Up To Date

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com