PMID- 36018390 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220830 IS - 1869-5760 (Print) IS - 1869-5760 (Electronic) IS - 1869-5760 (Linking) VI - 12 IP - 1 DP - 2022 Aug 26 TI - Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response. PG - 27 LID - 10.1186/s12348-022-00305-2 [doi] LID - 27 AB - 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. CI - (c) 2022. The Author(s). FAU - van Romunde, Saskia H M AU - van Romunde SHM AD - Department of Vitreoretinal surgery, Rotterdam Eye Hospital, Schiedamse Vest 180 - 3011BH, Rotterdam, the Netherlands. s.vanromunde@oogziekenhuis.nl. FAU - Vergouwen, Daphne P C AU - Vergouwen DPC AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. FAU - Iacovello, Daniela AU - Iacovello D AD - Department of Ophthalmology, IRCCS Sacro Cuore Don Calabria, Viale Rizzardi, 437024, Negrar, Italy. FAU - Roelen, Dave L AU - Roelen DL AD - Department of Immunology, Leiden Universitary Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands. FAU - Verdijk, Robert M AU - Verdijk RM AD - Department of Vitreoretinal surgery, Rotterdam Eye Hospital, Schiedamse Vest 180 - 3011BH, Rotterdam, the Netherlands. AD - Department of Pathology, Section Ophthalmic Pathology, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. AD - Department of Pathology, Leiden Universitary Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands. FAU - Ten Berge, Josianne C E M AU - Ten Berge JCEM AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. FAU - Pertile, Grazia AU - Pertile G AD - Department of Ophthalmology, IRCCS Sacro Cuore Don Calabria, Viale Rizzardi, 437024, Negrar, Italy. FAU - Schreurs, Marco W J AU - Schreurs MWJ AD - Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. FAU - van Meurs, Jan C AU - van Meurs JC AD - Department of Vitreoretinal surgery, Rotterdam Eye Hospital, Schiedamse Vest 180 - 3011BH, Rotterdam, the Netherlands. AD - Department of Ophthalmology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. LA - eng GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ GR - 6.1.0/Stichting Combined Ophthalmic Research Rotterdam/ PT - Journal Article DEP - 20220826 PL - Germany TA - J Ophthalmic Inflamm Infect JT - Journal of ophthalmic inflammation and infection JID - 101553216 PMC - PMC9418395 OTO - NOTNLM OT - Age-related macular degeneration OT - Antibodies OT - Immunofluorescence OT - Submacular surgery OT - Western blot COIS- The authors declare that they have no competing interests. EDAT- 2022/08/27 06:00 MHDA- 2022/08/27 06:01 PMCR- 2022/08/26 CRDT- 2022/08/26 11:16 PHST- 2022/03/13 00:00 [received] PHST- 2022/08/11 00:00 [accepted] PHST- 2022/08/26 11:16 [entrez] PHST- 2022/08/27 06:00 [pubmed] PHST- 2022/08/27 06:01 [medline] PHST- 2022/08/26 00:00 [pmc-release] AID - 10.1186/s12348-022-00305-2 [pii] AID - 305 [pii] AID - 10.1186/s12348-022-00305-2 [doi] PST - epublish SO - J Ophthalmic Inflamm Infect. 2022 Aug 26;12(1):27. doi: 10.1186/s12348-022-00305-2.