PMID- 32046454 OWN - NLM STAT- MEDLINE DCOM- 20201215 LR - 20201215 IS - 1933-7205 (Electronic) IS - 1933-7191 (Print) IS - 1933-7191 (Linking) VI - 27 IP - 5 DP - 2020 May TI - Upregulation of HLA-Class I and II in Placentas Diagnosed with Villitis of Unknown Etiology. PG - 1129-1138 LID - 10.1007/s43032-019-00101-9 [doi] AB - The placenta utilizes many mechanisms to protect the haploidentical fetus from recognition by the maternal immune system. However, in cases of villitis of unknown etiology (VUE), maternal lymphocytes gain access into the placenta, causing significant health risks for the fetus. Evidence suggests that VUE is a rejection response between the mother and the haploidentical fetus. Therefore, we profiled human leukocyte antigen (HLA), an important predictor of transplant rejection, in VUE using placental tissue from ten patients with VUE and ten gestational age matched controls. Placentas were stained using novel multiplexed immunofluorescence (MxIF) to investigate morphology and HLA classes I and II. Gene expression was evaluated by microarray, and where available, tissue typing of mother/baby pairs was completed to determine HLA type. MxIF demonstrated strong CD8+ T cell infiltration and HLA class I staining both the distal and stem villi of VUE placentas. Compared to controls, VUE cases had significantly higher expression of HLA class II mRNA and pathway analysis demonstrated that 40% of the differentially expressed genes in VUE are related to tissue rejection. The data suggest that VUE resembles a rejection response between the mother and the fetus. It remains unknown what initiates immune recognition and why some mothers appear to be at higher risk for developing this condition than others. Understanding this etiology will be critical for developing effective interventions or prevention strategies during pregnancy. FAU - Enninga, Elizabeth Ann L AU - Enninga EAL AD - Department of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Enninga.elizabethann@mayo.edu. FAU - Leontovich, Alexey A AU - Leontovich AA AD - Department of Health Science Research, Mayo Clinic, Rochester, MN, USA. FAU - Fedyshyn, Bohdana AU - Fedyshyn B AD - Department of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Wakefield, Laurie AU - Wakefield L AD - Department of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Gandhi, Manish AU - Gandhi M AD - Department of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Markovic, Svetomir N AU - Markovic SN AD - Department of Immunology, Mayo Clinic, Rochester, MN, USA. FAU - Ruano, Rodrigo AU - Ruano R AD - Department of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. FAU - Kerr, Sarah E AU - Kerr SE AD - Department of Laboratory Pathology, Mayo Clinic, Rochester, MN, USA. LA - eng GR - K12 HD065987/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200106 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 RN - 0 (HLA Antigens) SB - IM MH - Chorionic Villi/*metabolism/pathology MH - Female MH - HLA Antigens/*metabolism MH - Humans MH - Inflammation/*metabolism/pathology MH - Lymphocytes/metabolism/pathology MH - Placenta/*metabolism/pathology MH - Placenta Diseases/*metabolism/pathology MH - Pregnancy MH - *Up-Regulation PMC - PMC7255550 MID - NIHMS1548331 OTO - NOTNLM OT - HLA OT - Inflammation OT - Placenta OT - Rejection OT - Villitis COIS- The authors declare that there are no conflicts of interest. EDAT- 2020/02/13 06:00 MHDA- 2020/12/16 06:00 PMCR- 2020/10/07 CRDT- 2020/02/13 06:00 PHST- 2019/05/23 00:00 [received] PHST- 2019/09/17 00:00 [accepted] PHST- 2020/02/13 06:00 [pubmed] PHST- 2020/12/16 06:00 [medline] PHST- 2020/02/13 06:00 [entrez] PHST- 2020/10/07 00:00 [pmc-release] AID - 10.1007/s43032-019-00101-9 [pii] AID - 101 [pii] AID - 10.1007/s43032-019-00101-9 [doi] PST - ppublish SO - Reprod Sci. 2020 May;27(5):1129-1138. doi: 10.1007/s43032-019-00101-9. Epub 2020 Jan 6.