Korean J Radiol.  2009 Feb;10(1):58-62. 10.3348/kjr.2009.10.1.58.

Induction of Upregulation and Downregulation of the T-Cell Activation Marker CD98 in Patients Undergoing Contrast-Enhanced CT with Iodinated Non-Ionic Dimeric Contrast Medium

• Bohm I
• Schild HH

• KMID: 1088679
• DOI: http://doi.org/10.3348/kjr.2009.10.1.58

Abstract

OBJECTIVE
This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9% +/- 10.8% vs. 38.8% +/- 16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.

Keyword

Contrast media; Adverse drug reaction; Drug hypersensitivity; Flow cytometry; CD98 antigen; T-cells

MeSH Terms

Adult
Antigens, CD98/*metabolism
Benzamides/diagnostic use/*pharmacology
Contrast Media/*pharmacology
Down-Regulation/*drug effects
Female
Flow Cytometry
Humans
Lymphocyte Activation
Male
Middle Aged
Propanolamines/diagnostic use/*pharmacology
T-Lymphocytes/*drug effects/immunology
*Tomography, X-Ray Computed
Triiodobenzoic Acids/diagnostic use/*pharmacology
Up-Regulation/*drug effects

Figure

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  Fig. 1 Chemical structure of iosimenol (upper panel) and iodixanol (lower panel).

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  Fig. 2 Representative fluorescence microscopy of peripheral white blood cells expressing CD98 after staining with monoclonal anti-CD98 antibody labelled with FITC (fluorescein isothiocyanate).

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  Fig. 3 Modulation of the CD98 expression under the influence of contrast media injection.A. Contrast media injection in patients that received iosimenol and iodixanol induced non-significant decrease of CD98 expression after one hour and significant decrease of CD98 expression in peripheral lymphocytes after 24 hours (*p < 0.04).B. CD98 expression in lymphocytes (%) ± standard deviation prior to and at one hour and at 24 hours after injection of either iosimenol (left diagram) or iodixanol (right diagram). Decrease of CD98 expression in patients that received iosimenol was significant after 24 hours (**p < 0.05).

Reference

1. Webb JA, Stacul F, Thomsen HS, Morcos SK. Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. Late adverse reactions to intravascular iodinated contrast media. Eur Radiol. 2003; 13:181–184. PMID: 12541128.

2. Christiansen C, Pichler WJ, Skotland T. Delayed allergy-like reactions to X-ray contrast media: mechanistic considerations. Eur Radiol. 2000; 10:1965–1975. PMID: 11305580.

3. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology. 1990; 175:621–628. PMID: 2343107.

4. Delayed allergy-like reactions to X-ray contrast media. Exploration of the problem. Eur Radiol. 1996; 6:1–24. PMID: 9403083.

5. Schild HH, Kuhl CK, Hübner-Steiner U, Böhm I, Speck U. Adverse events after unenhanced and monomeric and dimeric contrast-enhanced CT: a prospective randomized controlled trial. Radiology. 2006; 240:56–64. PMID: 16720865.

6. Mikkonen R, Kontkanen T, Kivisaari L. Acute and late adverse reactions to low-osmolal contrast media. Acta Radiol. 1995; 36:72–76. PMID: 7833173.

7. Böhm I, Schild HH. A practical guide to diagnose lesser-known immediate and delayed contrast media-induced adverse cutaneous reactions. Eur Radiol. 2006; 16:1570–1579. PMID: 16770655.

8. Lapi F, Cecchi E, Pedone C, Attanasio F, Banchelli G, Vannacci A, et al. Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals. Eur J Clin Pharmacol. 2008; 64:723–737. PMID: 18401577.

9. Beeler A, Zaccaria L, Kawabata T, Gerber BO, Pichler WJ. CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity. Allergy. 2008; 63:181–188. PMID: 18005225.

10. Torres MJ, Mayorga C, Cornejo-Garcia JA, Lopez S, Chaves P, Rondon C, et al. Monitoring non-immediate allergic reactions to iodine contrast media. Clin Exp Immunol. 2008; 152:233–238. PMID: 18341616.

11. Lerch M, Keller M, Britschgi M, Kanny G, Tache V, Schmid DA, et al. Cross-reactivity patterns of T cells specific for iodinated contrast media. J Allergy Clin Immunol. 2007; 119:1529–1536. PMID: 17412404.

12. Kanny G, Pichler W, Morisset M, Franck P, Marie B, Kohler C, et al. T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests. J Allergy Clin Immunol. 2005; 115:179–185. PMID: 15637566.

13. Delgado-Jimenez Y, Perez-Gala S, Aragüés M, Sanchez-Perez J, Garcia-Diez A. Late skin reaction to iodixanol (Visipaque): clinical manifestations, patch test study, and histopathological evaluation. Contact Dermatitis. 2006; 55:348–353. PMID: 17101010.

14. Komada H, Imai A, Hattori E, Ito M, Tsumura H, Onoda T, et al. Possible activation of murine T lymphocyte through CD98 is independent of interleukin 2/interleukin 2 receptor system. Biomed Res. 2006; 27:61–67. PMID: 16707844.

15. Cho JY, Skubitz KM, Katz DR, Chain BM. CD98-dependent homotypic aggregation is associated with translocation of protein kinase Cdelta and activation of mitogen-activated protein kinases. Exp Cell Res. 2003; 286:1–11. PMID: 12729789.

16. Cho JY, Fox DA, Horejsi V, Sagawa K, Skubitz KM, Katz DR, et al. The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood. 2001; 98:374–382. PMID: 11435306.

17. Cai S, Bulus N, Fonseca-Siesser PM, Chen D, Hanks SK, Pozzi A, et al. CD98 modulates integrin beta1 function in polarized epithelial cells. J Cell Sci. 2005; 118:889–899. PMID: 15713750.

18. Suga K, Katagiri K, Kinashi T, Harazaki M, Iizuka T, Hattori M, et al. CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1. FEBS Lett. 2001; 489:249–253. PMID: 11165259.

19. Shikano N, Kanai Y, Kawai K, Ishikawa N, Endou H. Characterization of 3-[125I]iodo-alpha-methyl-L-tyrosine transport via human L-type amino acid transporter 1. Nucl Med Biol. 2003; 30:31–37. PMID: 12493540.

20. Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G, et al. Thyroid hormone transport by the heterodimeric human system L amino acid transporter. Endocrinology. 2001; 142:4339–4348. PMID: 11564694.

21. Su TZ, Feng MR, Weber ML. Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. J Pharmacol Exp Ther. 2005; 313:1406–1415. PMID: 15769862.

22. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, et al. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002; 61:729–737. PMID: 11901210.

23. Yan Y, Dalmasso G, Sitaraman S, Merlin D. Characterization of the human intestinal CD98 promoter and its regulation by interferon-gamma. Am J Physiol Gastrointest Liver Physiol. 2007; 292:G535–G545. PMID: 17023546.

24. Yao SY, Muzyka WR, Cass CE, Cheeseman CI, Young JD. Evidence that the transport-related proteins BAT and 4F2hc are not specific for amino acids: induction of Na+-dependent uridine and pyruvate transport activity by recombinant BAT and 4F2hc expressed in Xenopus oocytes. Biochem Cell Biol. 1998; 76:859–865. PMID: 10353721.

25. Nakamura E, Sato M, Yang H, Miyagawa F, Harasaki M, Tomita K, et al. 4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer. J Biol Chem. 1999; 274:3009–3016. PMID: 9915839.

26. Layseca-Espinosa E, Baranda L, Alvarado-Sanchez B, Portales-Perez D, Portillo-Salazar H, Gonzalez-Amaro R. Rolipram inhibits polarization and migration of human T lymphocytes. J Invest Dermatol. 2003; 121:81–87. PMID: 12839567.

27. Gonzalez-Amaro R, Portales-Perez D, Baranda L, Redondo JM, Martinez-Martinez S, Yanez-Mo M, et al. Pentoxifylline inhibits adhesion and activation of human T lymphocytes. J Immunol. 1998; 161:65–72. PMID: 9647208.

28. Taylor ML, Noble PW, White B, Wise R, Liu MC, Bochner BS. Extensive surface phenotyping of alveolar macrophages in interstitial lung disease. Clin Immunol. 2000; 94:33–41. PMID: 10607488.

29. Harada N, Nagasaki A, Hata H, Matsuzaki H, Matsuno F, Mitsuya H. Down-regulation of CD98 in melphalan-resistant myeloma cells with reduced drug uptake. Acta Haematol. 2000; 103:144–151. PMID: 10940652.

30. Ritchie JW, Peter GJ, Shi YB, Taylor PM. Thyroid hormone transport by 4F2hc-IU12 heterodimers expressed in Xenopus oocytes. J Endocrinol. 1999; 163:R5–R9. PMID: 10556789.