Akrep Antivenomunun İmmunassay Yöntem Üzerindeki İnterferans Etkisinin Deneysel Araştırılması

Skorpionizmde özgün tedavi yöntemi antivenom kullanımıdır. Antivenomların klinik olarak alerjik reaksiyonlara yol açtığı bilinse de antikor özelliğinden dolayı immunassay ölçüm yöntemlerinde oluşturabileceği interferans etkisi bilinmemektedir. İmmunassay metotlar hormon, kardiyak markır, tümör markırı ve pek çok büyük moleküllü parametrenin ölçülmesinde kullanılmaktadır. Birçok çalışmada farklı antikorların neden olduğu interferans gösterilmiş fakat aynı durumun antivenomlar tarafından da olabileceği gösterilmemiştir. Bu çalışmanın amacı akrep antivenomunun immunassay yöntemde interferans oluşturma potansiyelinin deneysel olarak araştırılmasıdır. Bu çalışmada akrep antivenomunun 23 adet immunassay test üzerindeki interferans etkileri incelendi. Çalışma sonucunda serbest T3 seviyesi yüksek titre antivenomda %13.09’luk bir sapma gösterdi. Fertilite testlerinden progesteron seviyesi düşük titrede %10.58 oranında, testosteron seviyesi %14.57 oranında negatif interferansa uğramıştır. Parathormon seviyelerinde düşük ve yüksek titre antivenom maruziyetinde %11-16 arasında negatif interferans gözlenmiştir. Kütle kreatin kinaz MB testi %7.35-21.58 oranında negatif interferansa, troponin I testi %3-8.9 oranında pozitif interferansa uğramıştır. Özellikle kardiyak testlerin yanlış negatif bulunması kardiyak komplikasyonların atlanmasına neden olacağından hayati öneme sahiptir. Tümör markırları içinde en çok negatif interferansa maruz kalan test %28.65-28.9 oranı ile kanser antijeni 19-9 oldu. Çoğu klinisyen tarafından bilinmeyen interfernas etki immunassay testlerde hatalı ölçüme neden olabilecek birer risk faktörüdür. Tedavi sırasında oluşabilecek bu tür durumlarla karşılaşmamak için hastane bilgi yönetim sistemleri ile klinisyenler önceden uyarılabilir. İnterferansın neden olduğu hatalı test sonuçları malpraktislerle karşılaşma riskini arttırmaktadır. Sonuç olarak klinisyenler immunassay tekniklerden daha iyi yöntemler bulunana kadar laboratuvar testlerini değerlendirirken interferansa karşı dikkatli olmalıdır.

Anahtar Kelimeler:

Skorpionizm, Antivenom, İnterferans, İmmunassay

Experimental Investigation of Interference Effect of Scorpion Antivenom on Immunoassay Method

The original treatment of scorpionism is intravenous antivenom infusion. It is known that antivenom causes clinically allergic reactions, however potential interference effect of scorpion antivenom is unknown . The aim of present study was to investigate the potential of antivenom interference in immunosassay methods. In this study, 50 uL and 100 uL scorpion antivenom was added to 23 immunassay tests used for measuring T3, progesterone, testosterone, parathormone, creatin kinase, cancer antigen and troponin-I concentrations. The free T3 level showed a deviation of 13.09% in high titer antivenom.Progesterone levels were low in the fertility test at 10.58% and testosterone level was 14.57% at the low level. Rate of free T3 deviation was 13.09% in high titer of antivenom. In fertility tests, it was observed that levels of progesterone and testosterone decreased between 10.58-14.57% in low titre antivenom exposure. Negative interference was observed between 11-16% in low and high titre antivenom at parathomone levels.Mass creatine kinase MB test exposured 7.35-21.58% negative interference and troponin-I test introduced positive interference. Especially, the false negative results of cardiac test have a vital proposition because it will cause cardiac complications to be skipped. The most negative interference was observed for Cancer Antigen 19-9 concentration with a rate of 28.65-28.9%. For all immunoassay measurements, every antibody is a risk factor that cause false negative or positive test result. Therefore, clinicians should be careful to confirm diagnostic laboratory tests until better methods than immunoassay techniques are found.

Keywords:

Scorpionism, Antivenom, Interference, Immunoassay,

PDF

___

Aydin S, 2015: A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides, 72, 4-15.
Bais R, 2010: The effect of sample hemolysis on cardiac troponin I and T assays. Clin Chem, 56, 1357-59.
Berth M, Bosmans E, Everaert J, Dierick J, Schiettecatte J, Anckaert E, Delanghe J, 2006: Rheumatoid factor interference in the determination of carbohydrate antigen 19-9 (CA 19-9). Clin Chem and Lab Med (CCLM), 44, 1137-39.
Cavalier E, Carlisi A, Chapelle JP, Delanaye P, 2008: False positive PTH results: an easy strategy to test and detect analytical interferences in routine practice. Clinica Chimica Acta, 387, 150-52.
Chatenoud L, Baudrihaye MF, Chkoff N, Kreis H, Goldstein G, Bach JF, 1986: Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3. The Journal of Immunology, 137, 830-38.
Covinsky M, Laterza O, Pfeifer JD, Farkas-Szallasi T, Scott MG, 2000: An IgM λ antibody to Escherichia coli produces false-positive results in multiple immunometric assays. Clin Chem, 46, 1157-61.
De Rezende, Alves N, Dias MB, Campolina D, Chavez-Olortegui C, Diniz CR, Santos Amaral CF, 1995: Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions. Am J Trop Med Hyg, 52, 277-80.
Eriksson S, Halenius H, Pulkki K, Hellman J, Pettersson K, 2005: Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies. Clin Chem, 51, 839-47.
Frödin JE , Lefvert AK, Mellstedt H, 1992: The clinical significance of HAMA in patients treated with mouse monoclonal antibodies. Cell biophysics, 21, 153-65.
García-González E, Aramendía M, Álvarez-Ballano D, Trincado P, Rello L, 2016: Serum sample containing endogenous antibodies interfering with multiple hormone immunoassays. Laboratory strategies to detect interference. Pract Lab Med, 4, 1-10.
Gulbahar O, Degertekin CK, Akturk M, Yalcin MM, Kalan I, Atikeler GF, Altinova AE, Yetkin I, Arslan M, Toruner F, 2015: A case with immunoassay interferences in the measurement of multiple hormones. The Journal of Clinical Endocrinology & Metabolism, 100, 2147-53.
Gutiérrez JM, León G, Lomonte B, 2003: Pharmacokinetic-pharmacodynamic relationships of immunoglobulin therapy for envenomation. Clin Pharmacokinet, 42, 721-41.
Ismail AAA, Walker PL, Barth JH, Lewandowski KC, Jones R, Burr WA, 2002: Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results. Clin Chem, 48, 2023-29.
Ismail AAA, Walker PL, Cawood ML, Barth JH, 2002: Interference in immunoassay is an underestimated problem. Ann Clin Biochem, 39, 366-73.
Khattabi A, Soulaymani-Bencheikh R, Achour S, Salmi LR, 2011: Classification of clinical consequences of scorpion stings: consensus development. Trans R Soc Trop Med Hyg, 105, 364-69.
Krahn J, Parry DM, Leroux M, Dalton J, 1999: High percentage of false positive cardiac troponin I results in patients with rheumatoid factor. Clin Biochem, 32, 477-80.
Marks, Vincent, 2002: False-positive immunoassay results: a multicenter survey of erroneous immunoassay results from assays of 74 analytes in 10 donors from 66 laboratories in seven countries. Clin Chem, 48, 2008-16.
McCarthy RC, Ryan FJ, McKenzie CM, 1988: Interference in immunoenzymometric assays caused by IgM anti-mouse IgG antibodies. Arch Pathol Lab Med, 112, 901-07.
Natrajan A, Sharpe D, Costello J, Jiang Q, 2010: Enhanced immunoassay sensitivity using chemiluminescent acridinium esters with increased light output. Anal Biochem, 406, 204-13.
Rauch P, Zellmer A, Dankbar N, Specht C, Sperling D, 2005: Assayoptimierung: Störeffekte bei Immunoassays erkennen und vermeiden. Laborwelt, 4, 33-39.
Sturgeon CM, Viljoen A, 2011: Analytical error and interference in immunoassay: minimizing risk. Ann Clin Biochem, 48, 418-32.
Taylor AE , Keevil B, Huhtaniemi IT, 2015: Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow. Eur J Endocrinol, 173, D1-D12.
Theakston RDG, Warrell DA, Griffiths E, 2003: Report of a WHO workshop on the standardization and control of antivenoms. Toxicon, 41, 541-57.
Valikhanfard-Zanjani E, Mirakabadi AZ, Oryan S, Goodarzi HR, Rajabi M, 2016: Specific Antivenom Ability in Neutralizing Hepatic and Renal Changes 24 Hours after Latrodectus dahli Envenomation. Journal of Arthropod-Borne Diseases, 10(2), 238-245.
Thompson M, Ellison SLR, 2008: A review of interference effects and their correction in chemical analysis with special reference to uncertainty. Accred Qual Assur, 10, 82–97.