Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response

Saskia H M van Romunde; Daphne P C Vergouwen; Daniela Iacovello; Dave L Roelen; Robert M Verdijk; Josianne C E M Ten Berge; Grazia Pertile; Marco W J Schreurs; Jan C van Meurs

doi:10.1186/s12348-022-00305-2

Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response

J Ophthalmic Inflamm Infect. 2022 Aug 26;12(1):27. doi: 10.1186/s12348-022-00305-2.

Authors

Affiliations

¹ Department of Vitreoretinal surgery, Rotterdam Eye Hospital, Schiedamse Vest 180 - 3011BH, Rotterdam, the Netherlands. s.vanromunde@oogziekenhuis.nl.
² Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
³ Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
⁴ Department of Ophthalmology, IRCCS Sacro Cuore Don Calabria, Viale Rizzardi, 437024, Negrar, Italy.
⁵ Department of Immunology, Leiden Universitary Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands.
⁶ Department of Vitreoretinal surgery, Rotterdam Eye Hospital, Schiedamse Vest 180 - 3011BH, Rotterdam, the Netherlands.
⁷ Department of Pathology, Section Ophthalmic Pathology, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
⁸ Department of Pathology, Leiden Universitary Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands.

Abstract

Purpose: Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach.

Methods: Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed.

Results: Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found.

Conclusions: Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.

Keywords: Age-related macular degeneration; Antibodies; Immunofluorescence; Submacular surgery; Western blot.

Abstract

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