Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation

Silviu Itescu, Thomas C. Tung, Elizabeth M. Burke, Alan Weinberg, Nader Moazami, John H. Artrip, Nicole Suciu-Foca, Eric A. Rose, Mehmet C. Oz, Robert E. Michler

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Background - Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. Methods and Results - The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti- MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P = 0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. Conclusions - These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

Original languageEnglish (US)
Pages (from-to)786-793
Number of pages8
JournalCirculation
Volume98
Issue number8
StatePublished - Aug 15 1998
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class II
Heart Transplantation
Major Histocompatibility Complex
Immunoglobulin G
Immunoglobulin Isotypes
Anti-Idiotypic Antibodies
Antibodies
Heart-Assist Devices
Tissue Donors
Histocompatibility Antigens Class I
HLA-A Antigens
Graft Rejection
Allografts
Blood Vessels
Heart Failure
Transplantation
Lymphocytes
Transplants
anti-IgG

Keywords

  • Antibodies
  • Risk factors
  • Transplantation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation. / Itescu, Silviu; Tung, Thomas C.; Burke, Elizabeth M.; Weinberg, Alan; Moazami, Nader; Artrip, John H.; Suciu-Foca, Nicole; Rose, Eric A.; Oz, Mehmet C.; Michler, Robert E.

In: Circulation, Vol. 98, No. 8, 15.08.1998, p. 786-793.

Research output: Contribution to journalArticle

Itescu, S, Tung, TC, Burke, EM, Weinberg, A, Moazami, N, Artrip, JH, Suciu-Foca, N, Rose, EA, Oz, MC & Michler, RE 1998, 'Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation', Circulation, vol. 98, no. 8, pp. 786-793.
Itescu, Silviu ; Tung, Thomas C. ; Burke, Elizabeth M. ; Weinberg, Alan ; Moazami, Nader ; Artrip, John H. ; Suciu-Foca, Nicole ; Rose, Eric A. ; Oz, Mehmet C. ; Michler, Robert E. / Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation. In: Circulation. 1998 ; Vol. 98, No. 8. pp. 786-793.
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AU - Itescu, Silviu

AU - Tung, Thomas C.

AU - Burke, Elizabeth M.

AU - Weinberg, Alan

AU - Moazami, Nader

AU - Artrip, John H.

AU - Suciu-Foca, Nicole

AU - Rose, Eric A.

AU - Oz, Mehmet C.

AU - Michler, Robert E.

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N2 - Background - Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. Methods and Results - The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti- MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P = 0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. Conclusions - These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

AB - Background - Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. Methods and Results - The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti- MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P = 0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. Conclusions - These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

KW - Antibodies

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