High-risk Corneal Allografts Are Capable of Stimulating Complement Dependent Cytolytic Antibodies

Hargrave, Sylvia L.; Taherzadeh, Sherine; Hegde, Sushma; Niederkorn, Jérry Y.

doi:10.1097/00003226-200007000-00024

Cited by 12 publications

(7 citation statements)

References 12 publications

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“…Ocular immune privilege, however, can be compromised under certain conditions with corneal transplantation. A previous study reported that allospecific complement‐dependent cytolytic Abs may be involved in the rejection of corneal allotransplantation . Increased C3a levels in the AH are a biomarker related to corneal xenograft rejection .…”

Section: Discussionmentioning

confidence: 97%

Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates

Yoon

Choi

et al. 2019

Xenotransplantation

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Background We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome. Methods Nine rhesus macaques undergoing full‐thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti‐CD20 antibody. Results Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7‐ month‐old) and younger (≤7‐month‐old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti‐αGal IgG/M levels were unchanged in both groups. At last examination, anti‐non‐Gal IgG was increased in the control group alone (P = .013). Conclusions The GTKOm pig corneal graft achieved long‐term survival when combined with anti‐CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.

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Section: Discussionmentioning

confidence: 97%

Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates

Yoon

Choi

et al. 2019

Xenotransplantation

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“…In corneal allotransplantation, a CD4 + T cell-mediated reaction is primarily involved in graft rejection [8,[61][62][63], while CD8 + T cell-and complement-mediated reactions are partially involved in allograft rejection [64][65][66][67].…”

Section: Rejection Mechanism In Corneal Xenotransplantation Through Vmentioning

confidence: 99%

Current Progress in Corneal Xenotransplantation

Kim¹

2017

Xenotransplantation - New Insights

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Blindness is a devastating situation, and one of the common causes is corneal blindness. Corneal transplantation is the standard treatment for the corneal blindness. The lack of human donors demands the exploration of alternative treatments such as corneal xenotransplantation and bioengineered corneas. We review the researches regarding immunological and physio-anatomical barriers of corneal xenotransplantation, recent progress of corneal xenotransplantation in nonhuman primate studies, and updates of regulatory guidelines to conduct clinical trials for corneal xenotransplantation. The current development of genetically-engineered and gene-editing technologies suggests that the promise much for the field of xenotransplantation. A clinical trial of xenotransplantation using a cellular porcine corneal stroma has already been conducted; however, safety concerns have not been reported so far. With regard to the regulatory aspects and preclinical efficacies, corneal xenotransplantation has become one of the clinically realistic options as human substitutes and progress in recent research is promising to advance corneal xenotransplantation field.

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“…However, the rejection can be CD8 T-cell mediated in CD4 knockout mice [25,26]. In addition, some reports have suggested a possible involvement of allospecific antibodies in corneal graft rejection, in a complement-dependent manner [27,28].…”

Section: Rejection Mechanism In Xenocorneal Transplantationmentioning

confidence: 99%

Xenocorneal transplantation

Kim¹,

Wee²,

Park³

et al. 2011

Current Opinion in Organ Transplantation

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High-risk Corneal Allografts Are Capable of Stimulating Complement Dependent Cytolytic Antibodies

Abstract: Allospecific corneal antibody may be involved in corneal graft rejection in high-risk donor-host combinations.

Cited by 12 publications

References 12 publications

Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates

Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates

Current Progress in Corneal Xenotransplantation

Xenocorneal transplantation

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