Abstract
Background Owing to contradictory results, HLA matching in penetrating keratoplasty still is equivocal. Different surgical techniques in multicentre studies, missing risk differentiation in high-risk situations, and faulty HLA typing can be identified as main reasons for these contradictory results. In this monocentre study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogeneous group of 418 normal-risk keratoplasty patients using serological typing techniques for HLA class I and immuno-genetic typing techniques for class II.
Methods Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0–2, group II with 3–6 mismatches in the A/B/DR loci). All surgery was carried out by three experienced surgeons according to a standardized scheme. Furthermore, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups with regard to the number of ABO or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft, and endothelial cell density of the graft at the end of organ culture. All HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and immunogenetically for HLA class II (DR locus).
Results At 4 years postoperatively, the ratio of clear and rejection-free graft survival was 92% in group I and 66% in group II (Kaplan–Meier estimation, log rank test, P=0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (P=0.03).
Conclusions In this monocentre study with proper typing techniques, the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogeneous group of normal-risk keratoplasty patients.
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References
Zirm E . Eine erfolgreiche totale Keratoplastik. Graefe's Arch Clin Exp Ophthalmol 1906; 64: 581–593.
Hill JC . The use of cyclosporine in high risk keratoplasty. Am J Ophthalmol 1989; 107: 506–510.
Hill JC . Systemic cyclosporine in high risk keratoplasty. Short-versus long-term therapy. Ophthalmology 1994; 101: 128–133.
Reinhard T, Hutmacher M, Sundmacher R, Godehardt E . Akute und chronische Immunreaktionen nach perforierender Keratoplastik mit normalem Immunrisiko. Klin Monatsbl Augenheilkd 1997; 210: 139–143.
Streilein J . Unraveling immune privilege. Science 1995; 270: 1158–1159.
Niederkorn JY, Mellon J . Anterior chamber-associated immune deviation promotes corneal allograft survival. Invest Ophthalmol Vis Sci 1996; 36: 1530–1540.
Yamada J, Streilein JW . Induction of anterior chamber-associated immune deviation by corneal allografts placed in the anterior chamber. Invest Ophthalmol Vis Sci 1997; 38: 2833–2843.
Sano Y, Okamoto S, Streilein JW . Induction of donor-specific ACAID can prolong orthotopic corneal allograft survival in ‘high-risk’ eyes. Curr Eye Res 1997; 16: 1171–1174.
Sundmacher R . Immunreaktionen nach Keratoplastik. Klin Monatsbl Augenheilkd 1977; 171: 705–722.
Sundmacher R, Stefansson A, Mackensen G . Verlaufsbeobachtungen nach Keratoplastik. Fortschr Ophthalmol 1983; 80: 224–227.
Opelz G, Mytilineos J, Scherer S, Dunckley H, Trejaut J, Chapman J et al. Analysis of HLA-DR matching in DNA-typed cadaver kidney transplants. Transplantation 1993; 55: 782–785.
Gibbs DC, Batchelor R, Werb A, Schlesinger W, Casey TA . The influence of tissue-type compatibility on the fate of full-thickness corneal grafts. Trans Ophthalmol Soc 1974; 94: 101–126.
Vannas S . Histocompatibility in corneal grafting. Invest Ophthalmol 1975; 14: 883–886.
Stark WJ, Hugh RT, Bias WB, Maumenee AE . Histocompatibility (HLA) antigens and keratoplasty. Am J Ophthalmol 1978; 86: 595–604.
Ehlers N, Kissmeyer-Nielsen F . Corneal transplantation and HLA histocompatibility. Acta Opthalmol 1979; 57: 738–741.
Foulks GN, Sanfilippo FP, Locasio JA, MacQueen JM, Dawson DV . Histocompatibility testing for keratoplasty in high-risk patients. Ophthalmology 1983; 90: 239–244.
Sanfilippo F, MacQueen JM, Vaughn WK, Foulks GN . Reduced graft rejection with good HLA-A and -B matching in high-risk corneal transplantation. New Engl J Med 1986; 315: 29–35.
Völker-Dieben HJ, D’Amaro J, Kruit PJ, Lange P . Interaction between prognostic factors for corneal allograft survival. Transplant Proc 1989; 21: 3135–3138.
Boisjoly HM, Roy R, Bernard PM, Dubé I, Laughrea PA, Bazin R . Association between corneal allograft reactions and HLA compatibility. Ophthalmology 1990; 97: 1689–1698.
Baggesen K, Ehlers N, Lamm LU . HLA-DR/RFLP compatible corneal grafts. Acta Ophthalmol 1991; 69: 229–233.
Beekhuis WH, van Rij G, Renardel de Lavalette JG, Rinkel-van Driel E, Persijn G, D’Amaro J . Corneal graft survival in HLA-A-and HLA-B-matched transplantations in high-risk cases with retrospective review of HLA-DR compatibility. Cornea 1991; 10: 9–12.
CCTS. Effectiveness of histocompatibility matching in high-risk corneal transplantation. Arch Ophthalmol 1992; 110: 1392–1403.
Vail A, Gore SM, Bradley BA, Easty DL, Rogers CA, Armitage WJ . Conclusions of the corneal transplant follow up study. Br J Ophthalmol 1997; 81: 631–636.
Hoffmann F, Pahlitzsch T . Predisposing factors in corneal graft rejection. Cornea 1989; 8: 215–219.
Hoffmann F, Tregel M, Noske W, Bünte S . HLA-B and -DR match reduces the allograft rejection after keratoplasty. Ger J Ophthalmol 1994; 3: 100–104.
Gore SM, Vail A, Bradley BA, Rogers CA, Easty DL, Armitage WJ . HLA-DR matching in corneal transplantation: systematic review of published data. Transplantation 1995; 110: 1392.
Reinhard T, Sundmacher R, Heering P . Systemic Cyclosporin A in high-risk keratoplasties. Graefe's Arch Clin Exp Ophththalmol 1996; 234 (Suppl 1): 115–121.
Hopkins KA, Maguire MG, Fink NE, Bias WB . Reproducibility of HLA-A, -B, and -DR typing using peripheral blood samples: results of retyping in the CCTS. Hum Immunol 1992; 22: 132.
Völker-Dieben HJ, Claas FHJ, Schreuder GMT, Schipper RF, Pels E, Persijn GG, Smits J, D’Amaro J . Beneficial effect of HLA-DR matching on the survival of corneal allografts. Transplantation 2000; 70: 640–648.
Wernet P, Kögler G, Enczmann J, Kuhröber A, Knipper A, Bonte W, Reinhard T, Sundmacher R . Rapid method for successful HLA Class I and II typing from cadaveric blood for direct matching in cornea transplantation. Graefe's Arch Clin Exp Ophthalmol 1998; 236: 507–512.
Pels L, Maas H, Tullo A . European Eye Bank Association Directory, 8th ed., 2000, EEBA, Amsterdam.
Böhnke M . Spendergewebe für die Keratoplastik. Klin Monatsbl Augenheilkd 1991; 198: 563–571.
Reinhard T, Holzwarth D, Spelsberg H, Dahmen N, Sundmacher R . Wissensbasierte Bildanalyse von Hornhauttransplantaten. Klin Monatsbl Augenheilkd 1999; 214: 407–411.
Hoffmann F . Nahttechnik bei perforierender Keratoplastik. Klin Mbl Augenheilk 1976; 169: 584–590.
Allredge OC, Krachmer JH . Clinical types of corneal transplant reaction. Arch Ophthalmol 1981; 99: 599–604.
Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Armitage WJ, Easty DL . Factors influencing the suitability of organ-cultured corneas for transplantation. Invest Ophthalmol Vis Sci 1997; 38: 16–24.
Borderie VM, Scheer S, Touzeau O . Donor organ cultured corneal tissue selection before penetrating keratoplasty. Br J Ophthalmol 1998; 82: 382–388.
Streilein JW . Immunobiology and immunopathology of corneal transplantation. In: Streilein JW (ed). Immune Response and the Eye. Chem Immunol, Vol 79. Karger: Basel, 1999, pp 186–206.
Newsome DA, Takasugi M, Kenyon K, Stark WF, Opelz G . Human corneal cells in vitro: morphology and histocompatibility antigens of pure cell populations. Invest Ophthalmol Vis Sci 1974; 13: 23–32.
Jager M . Corneal Langerhans cells and ocular immunology. Regional Immunol 1992; 4: 186–195.
Donelly JJ, Li W, Rockey JH, Prendergast RA . Induction of class II alloantigen expression on corneal endothelium in vivo and in vitro. Invest Ophthalmol Vis Sci 185; 26: 575–580.
Young E, Stark WJ, Prendergast RA . Immunology of corneal allograft rejection: HLA-DR antigens on human corneal cells. Invest Ophthalmol Vis Sci 1985; 26: 571–574.
Vilcek J, Jumming L . Inferon gamma. In: Delves PJ, Roitt IM (eds). Encyclopedia of Immunology. Academic Press: San Diego, 1999, pp 1421–1426.
Reis A, Megahed H, Reinhard T, Godehardt E, Spelsberg H, Braunstein S et al. Coadministration of the new macrolide RAD and Mycophenolate mofetil in experimental corneal transplantation. Transplantation 2000; 70: 1397–1401.
Beekhuis WH . Langzeitergebnisse bei HLA-A und B gematchter Hochrisiko-Keratoplastik. Ophthalmologe 2001; 98: S6–S7.
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This work was supported by the Bio Implant ServicesLeiden, NL
Proprietary interest: None
A special symposium took place on 30 September 2001 at Berlin which covered many problems and questions beyond the scope of this paper. The proceedings of this symposium will be published in a booklet separately
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Reinhard, T., Böhringer, D., Enczmann, J. et al. Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching. Eye 18, 269–277 (2004). https://doi.org/10.1038/sj.eye.6700636
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DOI: https://doi.org/10.1038/sj.eye.6700636
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