The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients

Amy B. Hahn, Gary N. Foulks, Cheryl Enger, Nancy Fink, Walter J. Stark, Katherine A. Hopkins, Fred Sanfilippo

Research output: Contribution to journalArticle

Abstract

The Collaborative Corneal Transplantation Studies are a pair of multicenter prospective clinical trials evaluating the effectiveness of histocompatibility matching in high risk keratoplasty patients. The antigen matching study (AMS) evaluated HLA matching in patients without circulating lymphocytotoxic antibody to HLA antigens and the cross-match study (CS) evaluated the effect of using cross-match-negative donors in patients with identified circulating lymphocytotoxic antibodies to HLA antigens. Sera from 510 patients considered for enrollment in the studies were screened preoperatively for the presence of anti-class I lymphocytotoxic antibodies (LA). The 42 patients (8%) found to have detectable LA entered the CS. The 468 patients found not to have detectable LA preoperatively entered the AMS. Fifteen of the 37 transplanted CS patients were found to have donor-specific anticlass I antibody (before or after surgery). These patients were also screened for anti-class II LA and 25 had anti-class II panel reactive antibody > 5%. Forty-nine of the 419 transplanted AMS patients (12%) were found to have produced anti-class I LA after surgery, and in 19 patients, antibody specificities were those of donor HLA antigens. There was a significant association between the number of mismatched class I antigens and the number of donor-specific LA produced. The production of LA by AMS patients was significantly associated with reaction episodes; eighty-two percent of patients (40 of 49) with LA had reaction, compared with 63% of patients (230 of 365) without LA (P=0.02). Likewise, production of donor-specific LA was significantly associated with immune-mediated graft failure (P=0.025). For CS patients, there was no correlation between the production of donor-specific anti-class I or nonspecific anti-class II antibodies and graft outcome. However, the CS patients had poorer graft survival than did AMS patients at 3 years (57% vs. 66%, P=0.01). These data demonstrate that LA, especially directed against donor class I HLA antigens following comeal transplantation in high risk patients, are associated with immune graft rejection and can be an indicator of allograft rejection.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalTransplantation
Volume59
Issue number1
StatePublished - Jan 15 1995

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Antilymphocyte Serum
Allografts
HLA Antigens
Tissue Donors
Antigens
Histocompatibility Antigens Class I
Corneal Transplantation
Transplants
Histocompatibility
Antibody Specificity
Antibodies
Immunoglobulin Isotypes
Graft Rejection
Graft Survival

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Hahn, A. B., Foulks, G. N., Enger, C., Fink, N., Stark, W. J., Hopkins, K. A., & Sanfilippo, F. (1995). The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients. Transplantation, 59(1), 21-27.

The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients. / Hahn, Amy B.; Foulks, Gary N.; Enger, Cheryl; Fink, Nancy; Stark, Walter J.; Hopkins, Katherine A.; Sanfilippo, Fred.

In: Transplantation, Vol. 59, No. 1, 15.01.1995, p. 21-27.

Research output: Contribution to journalArticle

Hahn, AB, Foulks, GN, Enger, C, Fink, N, Stark, WJ, Hopkins, KA & Sanfilippo, F 1995, 'The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients', Transplantation, vol. 59, no. 1, pp. 21-27.
Hahn AB, Foulks GN, Enger C, Fink N, Stark WJ, Hopkins KA et al. The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients. Transplantation. 1995 Jan 15;59(1):21-27.
Hahn, Amy B. ; Foulks, Gary N. ; Enger, Cheryl ; Fink, Nancy ; Stark, Walter J. ; Hopkins, Katherine A. ; Sanfilippo, Fred. / The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients. In: Transplantation. 1995 ; Vol. 59, No. 1. pp. 21-27.
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abstract = "The Collaborative Corneal Transplantation Studies are a pair of multicenter prospective clinical trials evaluating the effectiveness of histocompatibility matching in high risk keratoplasty patients. The antigen matching study (AMS) evaluated HLA matching in patients without circulating lymphocytotoxic antibody to HLA antigens and the cross-match study (CS) evaluated the effect of using cross-match-negative donors in patients with identified circulating lymphocytotoxic antibodies to HLA antigens. Sera from 510 patients considered for enrollment in the studies were screened preoperatively for the presence of anti-class I lymphocytotoxic antibodies (LA). The 42 patients (8{\%}) found to have detectable LA entered the CS. The 468 patients found not to have detectable LA preoperatively entered the AMS. Fifteen of the 37 transplanted CS patients were found to have donor-specific anticlass I antibody (before or after surgery). These patients were also screened for anti-class II LA and 25 had anti-class II panel reactive antibody > 5{\%}. Forty-nine of the 419 transplanted AMS patients (12{\%}) were found to have produced anti-class I LA after surgery, and in 19 patients, antibody specificities were those of donor HLA antigens. There was a significant association between the number of mismatched class I antigens and the number of donor-specific LA produced. The production of LA by AMS patients was significantly associated with reaction episodes; eighty-two percent of patients (40 of 49) with LA had reaction, compared with 63{\%} of patients (230 of 365) without LA (P=0.02). Likewise, production of donor-specific LA was significantly associated with immune-mediated graft failure (P=0.025). For CS patients, there was no correlation between the production of donor-specific anti-class I or nonspecific anti-class II antibodies and graft outcome. However, the CS patients had poorer graft survival than did AMS patients at 3 years (57{\%} vs. 66{\%}, P=0.01). These data demonstrate that LA, especially directed against donor class I HLA antigens following comeal transplantation in high risk patients, are associated with immune graft rejection and can be an indicator of allograft rejection.",
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AB - The Collaborative Corneal Transplantation Studies are a pair of multicenter prospective clinical trials evaluating the effectiveness of histocompatibility matching in high risk keratoplasty patients. The antigen matching study (AMS) evaluated HLA matching in patients without circulating lymphocytotoxic antibody to HLA antigens and the cross-match study (CS) evaluated the effect of using cross-match-negative donors in patients with identified circulating lymphocytotoxic antibodies to HLA antigens. Sera from 510 patients considered for enrollment in the studies were screened preoperatively for the presence of anti-class I lymphocytotoxic antibodies (LA). The 42 patients (8%) found to have detectable LA entered the CS. The 468 patients found not to have detectable LA preoperatively entered the AMS. Fifteen of the 37 transplanted CS patients were found to have donor-specific anticlass I antibody (before or after surgery). These patients were also screened for anti-class II LA and 25 had anti-class II panel reactive antibody > 5%. Forty-nine of the 419 transplanted AMS patients (12%) were found to have produced anti-class I LA after surgery, and in 19 patients, antibody specificities were those of donor HLA antigens. There was a significant association between the number of mismatched class I antigens and the number of donor-specific LA produced. The production of LA by AMS patients was significantly associated with reaction episodes; eighty-two percent of patients (40 of 49) with LA had reaction, compared with 63% of patients (230 of 365) without LA (P=0.02). Likewise, production of donor-specific LA was significantly associated with immune-mediated graft failure (P=0.025). For CS patients, there was no correlation between the production of donor-specific anti-class I or nonspecific anti-class II antibodies and graft outcome. However, the CS patients had poorer graft survival than did AMS patients at 3 years (57% vs. 66%, P=0.01). These data demonstrate that LA, especially directed against donor class I HLA antigens following comeal transplantation in high risk patients, are associated with immune graft rejection and can be an indicator of allograft rejection.

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