Susceptibility of Lung Transplants to Preformed Donor-Specific Hla Antibodies as Detected by Flow Cytometry

Abstract

Class II, and perhaps class I HLA antibodies at relatively low concentrations represent a risk factor for severe early pulmonary graft dysfunction, with the potential to progress to hyperacute rejection and death.

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

“…Development of Abs against the donor-mismatched HLA Ags has been shown to correlate with the development of chronic rejection in transplant recipients, and the development of Ab has been shown to precede clinical evidence of chronic rejection (12,21). Studies from our laboratory (11) and others (22)(23)(24) have demonstrated that posttransplant development of anti-HLA Abs correlate with development of BOS following human lung transplantation. However, a substantial proportion of the transplant recipients, despite the absence of development of any detectable Abs against donor-mismatched HLA Ags, undergo chronic rejection, and in many of these cases Ab as well as complement deposition have been observed in their grafts (25)(26)(27).…”

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

“…Preformed anti-donor class II antibodies increase the risk of transplant failure [1][2][3][4][5][6][7][8][9] and the post-transplant development of anti-class II antibodies is associated with a higher incidence of acute and chronic rejection [10][11][12][13][14][15][16][17][18][19] Current class II matching strategies for kidney transplantation consider only the HLA-DR antigens controlled by the DRB1 locus but mismatching for HLA-DQ and HLA-DP may also lead to lower graft survival rates [20][21][22][23][24][25]. Newer serum screening methods such as ELISA, Flow Cytometry and Luminex have greatly enhanced the detection of anti-HLA-DQ and HLA-DP antibodies and their association with transplant rejection [2,7,[26][27][28][29].…”

Successful lung transplantation in the presence of pre-existing donor-specific cytotoxic HLA Class II antibodies

“…Antibodies to the 60QF epitope have been described previously and were found in 32% of patients with a failing kidney allograft. 21 In cohort studies on lung transplantation, the effect of pre-existing donor-specific anti-HLA antibodies on rejection and (graft) survival is difficult to evaluate, because only 5% to 15% of patients have elevated PRA levels prior to transplantation, 5,14,15 in contrast to 25% to 50% of kidney transplant patients on the waiting list. 22 Nevertheless, in two large studies (656 and 10,000 patients, respectively), decreased survival was reported in lung transplant recipients with a pre-transplant PRA exceeding 25%.…”

“…Although some studies could not identify differences in graft failure between sensitized and unsensitized patients, 6,13 most have shown that antibodies against HLA are associated with early graft dysfunction and decreased survival in lung transplant recipients. 5,14,15 However, these studies did not discriminate between donor-specific and non-donor-directed HLA antibodies. The effect of PRA on the allograft might therefore be due to donor-specific anti-HLA antibodies, but the concordant existence of antibodies toward non-HLA antigens or a general increased immune responsiveness could also play a role.…”

“…4 However, in lung transplantation the significance of pre-existing HLAspecific antibodies has not been fully established, which may be partly due to the low incidence of humoral sensitization in the lung transplant population. 5,6 Several cases of severe graft failure due to hyperacute rejection caused by pre-existing donor-specific anti-HLA antibodies have been reported, 7-12 but hyperacute rejection is a rare event after lung transplantation. The degree of humoral sensitization of a patient is determined by measuring http://www.jhltonline.org antibody-mediated reactivity toward a defined panel of HLA antigens (panel-reactive antibody, or PRA).…”