Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders

Yıl: 2019 Cilt: 45 Sayı: 4 Sayfa Aralığı: 31 - 37 Metin Dili: İngilizce DOI: 10.4999/uhod.193047 İndeks Tarihi: 18-06-2020

Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders

Öz:
In myeloproliferative disorders (MPDs), vitamin B12 levels are measured falsely elevated with conventional methods due to increasedcarrier protein synthesis. HoloTranscobalamine (HoloTC) assay is a first-choice method for detecting true vitamin B12 deficiency inMPDs. Our aim was to determine effects of immune complexes on HoloTC assay. This is a cross-section study. Vitamin B12 levels in61 patients with myeloproliferative disorders were measured by both electrochemical immunoassay and HoloTC assay. The HoloTCcutoff was greater than 35 pmol/L. HoloTC assay for each sample were repeated after polyethylene glycol (PEG) treatment to exclude IgG, IgA and IgM type immune complexes. Also, methylmalonic acid, folate, homocystein, liver, and kidney function tests wereobtained. Methylmalonic acid test showed that 42 patients (68.9%) had vitamin B12 deficiency. Vitamin B12 levels by HoloTC assaydecreased by 19.2±11.28% in essential thrombocytosis, 40.0±9.39% in chronic myeloid leukemia, 30.9±14.62% in myelofibrosisand 21.2±11.55% in polycythemia vera patients after PEG treatment. There was significant difference between the averages of groups(p< 0.01). Methylmalonic Acid Test was used as the B12 status variable. The comparison of ROC curves of HoloTC before and afterPEG showed no statistically significance between area under curves. The optimum cut-off points for both HoloTC before and afterPEG were 40.6 pmol/L and 32.1 pmol/L, respectively. Immune complexes may have some effect on HoloTC assay which has been recently reported to have a superior diagnostic accuracy for vitamin B12 deficiency in patients with MPDs. Although exclusion of immunecomplexes did not improve its diagnostic performances, effects of exclusion were significantly different between subgroups of MPDs.
Anahtar Kelime:

A comparison between the efficacy and safety of microscopic inguinal and subinguinal varicocelectomy

Öz:
Objective: To compare microscopic inguinal (MIV) and subinguinal varicocelectomy (MSV) surgeries with respect to efficacy and safety.Material and methods: Patients who underwent varicocelectomy between January 2002 and January2018 were evaluated retrospectively and prospectively. The patients who underwent varicocelectomyuntil December 2015 were analyzed retrospectively and the cases after January 2016 were analyzedprospectively. In our study, the married infertile male cases were compared on the basis of operationduration, number of ligated veins, number of preserved veins, postoperative pain score (visual analogue scale: VAS), patient satisfaction, surgeon satisfaction, changes in sperm parameters, testicularconsistency, pregnancy rates, and complications, such as hydrocele, testicular atrophy, and recurrenceof varicocele. Surgical success rates were compared by semen analysis between unmarried infertilemale cases because pregnancy rates cannot be tested. The patients were recalled for control examinations every 3 months for 1 year and tested the above-mentioned parameters. Statistical Package for theSocial Sciences Version 20 Windows Software was used for data analysis and comparison between thetwo groups.Results: The study included a total of 136 adult patients. Mean age of the patients was 28.14 (20–41)years. MSV and MIV were performed in 62 (45.6%) and 74 (54.4%) patients, respectively. No statistically significant difference was detected between the two groups in terms of admission duration, semenparameters within the 1-year follow-up process, hormonal changes, and complication rates. Operationduration was significantly longer in the MSV group. It was determined that a fewer number of veinswere ligated, and a fewer number of veins needed to be ligated in the MIV group. The analysis of allthe patients revealed that pain scores at 4 and 24 hours postoperatively were significantly statisticallylower in the MSV group.Conclusion: MIV and MSV are distinct, efficient, and safe surgical techniques with specific advantages and disadvantages. Their efficacy and safety rates are similar.
Anahtar Kelime:

İmmün Kompleksler Myeloproliferatif Hastalıklarda B12 Vitamin Eksikliğinin Holotranskobalamin Testini Etkileyebilir

Öz:
Miyeloproliferatif hastalıklarda (MPH), artan taşıyıcı protein sentezi nedeniyle, vitamin B12 düzeylerinin, geleneksel yöntemlerle ölçümünde bazı zorluklar yaşanmaktadır HoloTranskobalamin (HoloTC) testi MPH’da gerçek B12 eksikliklerini tespit etmek için ilk seçilecek testlerden birisidir. Bu çalışmadaki amacımız immunkomplekslerin HoloTC testi üzerindeki etkilerini tespit etmektir. Bu araştırma, Kesitsel bir çalışmadır. Hastanemizin Hematoloji Kliniğine başvuran ve MPH tanısı ile takip edilen 61 hastanın Vitamin B12 düzeyleri hem elektro-kimyasal immünassay hem de HoloTC testi ile çalışıldı. Aynı örnekler immün kompleksleri çöktürmek için polyetilen glikol (PEG) ile muamele edildikten sonra HoloTC testi tekrar edildi. Aynı zamanda, metilmalonik asit, folat, homosistein düzeyleri ile birlikte karaciğer ve böbrek testleri yapıldı. Metilmalonik asit testi ile 42 hastanın (%68.9), vitamin B12 eksikliği tespit edildi. PEG muamelesinden sonra HoloTC testi ile Vitamin B12 düzeyleri essansiyel trombositosis hastalarında %19.2±11.28, kronik myeloid lösemi hastalarında %40.0±9.39, myelofibrosis’te %30.9±14.62% ve polistemiya vera (PV) hastalarında ise 21.2±11.55% oranlarında azaldı. Grupların ortalamaları arasında istatistiksel anlamlı fark bulundu (p< 0.01). B12 durum değişkeni olarak Metilmalonik Asit Testi alındı. PEG uygulaması öncesi ve sonrası HoloTC testlerinin ROC eğrileri karşılaştırıldı. Her iki durumun eğri altında kalan alanları istatistiksel olarak anlamlı bir farklılık göstermedi. Optimum “cut-off” noktaları PEG öncesi HoloTC için 40.6 pmol/L; PEG sonrası için ise 32.1 pmol/L olarak tespit edildi. Son zamanlarda myeloproliferatif hastalıklarda tanısal doğruluğu gösterilmiş olan HoloTC testi, bu hastalıklarda oluşan immun komplekslerden etkilenebilir. İmmun komplekslerin ekarte edilmesi bu testin diagnostik performansını etkilememekle birlikte etkileri hastalık gruplarına göre anlamlı olarak farklık göstermektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Cayan S, Shavakhabov S, Kadioglu A. Treatment of palpable varicocele in infertile men: a meta-analysis to define the best tech-nique. J Androl 2009;30:33-40. [CrossRef]
  • 1. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ 349: g5226, 2014.
  • 2. Lv JX, Wang LL, Wei XD, Zhang Z, Zheng TL, Huang YH, et al., Comparison of Treatment Outcomes of Different Spermatic Vein Ligation Procedures in Varicocele Treatment. Am J Ther 2016;23:1329-34. [CrossRef]
  • 2. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician 67: 979-986, 2003.
  • 3. Söylemez H, Penbegül N, Atar M, Bozkurt Y, Sancaktutar AA, Al-tunoluk B. Comparison of laparoscopic and microscopic subingui-nal varicocelectomy in terms of postoperative scrotal pain. JSLS 2012;16:212-7. [CrossRef]
  • 3. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med 368: 149-160, 2013.
  • 4. Cayan S, Erdemir F, Ozbey I, Turek PJ, Kadioğlu A, Tellaloğlu S. Can varicocelectomy significantly change the way couples use assisted re-productive technologies? J Urol 2002;167:1749-52. [CrossRef] 5. Palomo A. Radical cure of varicocele by a new technique; prelimi-nary report. J Urol 1949;61:604-7. [CrossRef]
  • 4. Healton EB, Savage DG, Brust JC, et al. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 70: 229-245, 1991.
  • 6. Glassberg KI, Poon SA, Gjertson CK, DeCastro GJ, Misseri R. Laparoscopic lymphatic sparing varicocelectomy in adolescents. J Urol 2008;180:326-31. [CrossRef]
  • 5. Golding PH. Holotranscobalamin (HoloTC, Active-B12) and Herbert’s model for the development of vitamin B12 deficiency: a review and alternative hypothesis. Springerplus 5: 668, 2016.
  • 7. Ivanissevich O. Left varicocele due to reflux; experience with 4,470 operative cases in forty-two years. J Int Coll Surg 1960;34:742-55. 8. Nabi G, Asterlings S, Greene DR, Marsh RL. Percutaneous em-bolization of varicoceles: outcomes and correlation of semen im-provement with pregnancy. Urology 2004;63:359-63. [CrossRef] 9. Watanabe M, Nagai A, Kusumi N, Tsuboi H, Nasu Y, Kumon H.
  • 6. Bench AJ, Cross NC, Huntly BJ, et al. Myeloproliferative disorders. Best Pract Res Clin Haematol 14: 531-551, 2001.
  • Minimal invasiveness and effectivity of subinguinal microscopic varicocelectomy: a comparative study with retroperitoneal high and laparoscopic approaches. Int J Urol 2005;12:892-8. [CrossRef]
  • 7. Faurschou M, Nielsen OJ, Jensen MK, Hasselbalch HC. High prevalence of hyperhomocysteinemia due to marginal deficiency of cobalamin or folate in chronic myeloproliferative disorders. Am J Hematol 65: 136-140, 2000.
  • 10. Cayan S, Kadioglu TC, Tefekli A, Kadioglu A, Tellaloglu S. Com-parison of results and complications of high ligation surgery and microsurgical high inguinal varicocelectomy in the treatment of varicocele. Urology 2000;55:750-4. [CrossRef]
  • 8. Woo KS, Kim KE, Park JS, et al. Relationship between the levels of holotranscobalamin and vitamin B12. Korean J Lab Med 30: 185-189, 2010.
  • 11. Orhan İ, Onur R, Yüzgeç V, Semerciöz A, Fatih F. Subinguinal Varikoselektomide Anatomik Vasküler Varyasyonlar. Fırat Tıp Dergisi 2004;9:18-20. 12. Nuhoğlu B, Göçen A, Ersoy E, Ayyıldız A, Fidan V, Germiyanoğlu C. Subinguinal mikrocerrahi ve inguinal varikoselektominin se-men ve hormon parametrelerine etkilerinin karsılaştırılması, 1 yıllık izlenim. Turk J Urol 2004;30:302-7.
  • 9. Gauchan D, Joshi N, Gill AS, et al. Does an elevated serum vitamin B(12) level mask actual vitamin B (12) deficiency inmyeloproliferative disorders? Clin Lymphoma Myeloma Leuk 12: 269-273, 2012.
  • 13. Yurdakul T, Gökçe G, Kısakol G, Kılınç M. İnfertil erkeklerde yük-sek inguinal ve mikrocerrahi ile subinguinal varikoselektominin karşılaştırılması. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2003;56. [CrossRef]
  • 10. Cinemre H, Serinkan Cinemre BF, Cekdemir D, et al. Diagnosis of vitamin B12 deficiency in patients with myeloproliferative disorders. J Investig Med 63: 636-640, 2015.
  • 14. Cerit N, Gamlı M, Örnek D, Özdoğan L, Erdoğan G, Kalaycı D, ve ark. Genel Anesteziye bağlı perioperatif dönemde gözlenen komplikasyonların ve nedenlerinin retrospektif değerlendirilmesi. J Anesthesia 2011;19:106-13.
  • 11. Cervantes F, Pereira A, Marti J, et al. Bone marrow lymphoid nodules in myeloproliferative disorders: association with the nonmyelosclerotic phases of idiopathic myelofibrosis and immunological significance Br J Haematol 70: 279-282, 1988.
  • 15. Pettersson S, Söderholm B, Persson JE, Eriksson S, Fritjofs-son A. Testicular blood flow in man measured with venous oc-clusion plethysmography and xenon133. Scand J Urol Nephrol 1973;7:115-9. [CrossRef]
  • 12. Hasselbach H. Idiopathic myelofibrosis: A clinical study of 80 patients. Am J Hematol 34: 291-300, 1990.
  • 16. Coolsaet BL. The varicocele syndrome: venography determining the optimal level for surgical management. J Urol 1980;124:833-9. [CrossRef]
  • 13. Centers for Disease Control and Prevention. National report on biochemical indicators of diet and nutrition in the US population 1999–2002. Atlanta, GA: National Center for Environmental Health, 2008.
  • 17. Beck EM, Schlegel PN, Goldstein M. Intraoperative varico-cele anatomy: a macroscopic and microscopic study. J Urol 1992;148:1190-4. [CrossRef]
  • 14. Jeffery J, Millar H, Mackenzie P, et al. An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations. Clin Biochem 43: 82-88, 2010.
  • 18. Süer E, Yaman Ö. Varikoselin tedavi endikasyonları, tedavi yön-temleri, prognostik faktörler ve komplikasyonlar. Erkek üreme sistemi hastalıkları ve tedavisi, ed. Aşçı R. İstanbul Tıp kitapevi Vol. 1. 2013.
  • 15. Baglin TP, Price SM, Boughton BJ. A reversible defect of platelet PDGF content in myeloproliferative disorders Br J Haematol 69: 483-486, 1988.
  • 19. Lv KL, Zhuang JT, Zhao L, Wan Z, Zhang YD, Gao Y, et al., Vari-cocele anatomy during subinguinal microsurgical varicocelectomy in Chinese men. Andrologia 2015;47:1190-5. [CrossRef]
  • 16. Marcus RE, Hibbin JA, Mattutes E. Megakaryoblastic transformation of myelofibrosis with expression of the csis oncogene. Scand J Haematol 36: 186-193, 1986.
  • 20. Hopps CV, Lemer ML, Schlegel PN, Goldstein M. Intraoperative varicocele anatomy: a microscopic study of the inguinal versus subinguinal approach. J Urol 2003;170:2366-70. [CrossRef]
  • 17. Aparicio-Ugarriza R, Palacios G, Alder M, GonzálezGross M. A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population. Clin Chem Lab Med 53: 1149-1159, 2015.
  • 21. Orhan İ, Onur R, Yüzgeç V, Semerciöz A, Fırdolaş F. Inguinal re-gion testicular artery and vein anatomy. Fırat Med J 1999;1:561-4.
  • 18. Morkbak AL, Heimdal RM, Emmens K, et al. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project. Clin Chem Lab Med 43: 1058-1064, 2005.
  • 22. Gontero P, Pretti G, Fontana F, Zitella A, Marchioro G, Frea B. Inguinal versus subinguinal varicocele vein ligation using magni-fying loupe under local anesthesia: which technique is preferable in clinical practice? Urology 2005;66:1075-9. [CrossRef]
  • 19. Miller JW, Garrod MG, Rockwood AL, et al. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem 52: 278-285, 2006.
APA ÇEKDEMIR D, DEMİRDÖĞEN Ş, cinemre f, ÖZKAYA F, AYDEMİR B, CİNİSLİOĞLU A, Dilaveroglu N, ALTAY M, Cekdemir Y, ADANUR Ş, Gunduz M, Polat Ö, Cinemre H, ÖZBEY İ (2019). Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. , 31 - 37. 10.4999/uhod.193047
Chicago ÇEKDEMIR DEMET,DEMİRDÖĞEN Şaban Oğuz,cinemre fatma behice,ÖZKAYA FATİH,AYDEMİR Birsen,CİNİSLİOĞLU AHMET EMRE,Dilaveroglu Nilgun,ALTAY MEHMET SEFA,Cekdemir Yasin ertug,ADANUR ŞENOL,Gunduz Mehmet,Polat Özkan,Cinemre Hakan,ÖZBEY İsa Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. (2019): 31 - 37. 10.4999/uhod.193047
MLA ÇEKDEMIR DEMET,DEMİRDÖĞEN Şaban Oğuz,cinemre fatma behice,ÖZKAYA FATİH,AYDEMİR Birsen,CİNİSLİOĞLU AHMET EMRE,Dilaveroglu Nilgun,ALTAY MEHMET SEFA,Cekdemir Yasin ertug,ADANUR ŞENOL,Gunduz Mehmet,Polat Özkan,Cinemre Hakan,ÖZBEY İsa Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. , 2019, ss.31 - 37. 10.4999/uhod.193047
AMA ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. . 2019; 31 - 37. 10.4999/uhod.193047
Vancouver ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. . 2019; 31 - 37. 10.4999/uhod.193047
IEEE ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ "Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders." , ss.31 - 37, 2019. 10.4999/uhod.193047
ISNAD ÇEKDEMIR, DEMET vd. "Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders". (2019), 31-37. https://doi.org/10.4999/uhod.193047
APA ÇEKDEMIR D, DEMİRDÖĞEN Ş, cinemre f, ÖZKAYA F, AYDEMİR B, CİNİSLİOĞLU A, Dilaveroglu N, ALTAY M, Cekdemir Y, ADANUR Ş, Gunduz M, Polat Ö, Cinemre H, ÖZBEY İ (2019). Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. Uluslararası Hematoloji-Onkoloji Dergisi, 45(4), 31 - 37. 10.4999/uhod.193047
Chicago ÇEKDEMIR DEMET,DEMİRDÖĞEN Şaban Oğuz,cinemre fatma behice,ÖZKAYA FATİH,AYDEMİR Birsen,CİNİSLİOĞLU AHMET EMRE,Dilaveroglu Nilgun,ALTAY MEHMET SEFA,Cekdemir Yasin ertug,ADANUR ŞENOL,Gunduz Mehmet,Polat Özkan,Cinemre Hakan,ÖZBEY İsa Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. Uluslararası Hematoloji-Onkoloji Dergisi 45, no.4 (2019): 31 - 37. 10.4999/uhod.193047
MLA ÇEKDEMIR DEMET,DEMİRDÖĞEN Şaban Oğuz,cinemre fatma behice,ÖZKAYA FATİH,AYDEMİR Birsen,CİNİSLİOĞLU AHMET EMRE,Dilaveroglu Nilgun,ALTAY MEHMET SEFA,Cekdemir Yasin ertug,ADANUR ŞENOL,Gunduz Mehmet,Polat Özkan,Cinemre Hakan,ÖZBEY İsa Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. Uluslararası Hematoloji-Onkoloji Dergisi, vol.45, no.4, 2019, ss.31 - 37. 10.4999/uhod.193047
AMA ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. Uluslararası Hematoloji-Onkoloji Dergisi. 2019; 45(4): 31 - 37. 10.4999/uhod.193047
Vancouver ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders. Uluslararası Hematoloji-Onkoloji Dergisi. 2019; 45(4): 31 - 37. 10.4999/uhod.193047
IEEE ÇEKDEMIR D,DEMİRDÖĞEN Ş,cinemre f,ÖZKAYA F,AYDEMİR B,CİNİSLİOĞLU A,Dilaveroglu N,ALTAY M,Cekdemir Y,ADANUR Ş,Gunduz M,Polat Ö,Cinemre H,ÖZBEY İ "Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders." Uluslararası Hematoloji-Onkoloji Dergisi, 45, ss.31 - 37, 2019. 10.4999/uhod.193047
ISNAD ÇEKDEMIR, DEMET vd. "Effects of Immune Complexes on Holotranscobalamine Assay of Vitamin B12 Deficiency in Myeloproliferative Disorders". Uluslararası Hematoloji-Onkoloji Dergisi 45/4 (2019), 31-37. https://doi.org/10.4999/uhod.193047