IntroductionIn pregnancy, the mother and fetus differ in HLA antigens, and yet the maternal immune system generally tolerates the fetus. KIR receptors expressed by maternal uterine NK cells at the maternal-fetal interface directly interact with HLA-C on extravillous trophoblast cells for optimal placental development. In this study, we aimed to determine whether there is a preferential selection for HLA compatibility and specific KIR/HLA-C combinations in uncomplicated and preeclamptic naturally conceived pregnancies compared to what would be expected by chance.MethodsGenotyping for maternal and fetal HLA-A, -B, -C, -DR, and -DQ, and maternal KIR was performed for 451 uncomplicated pregnancies and 77 pregnancies complicated with preeclampsia. The number of HLA antigen (mis)matches between mother and fetus was calculated and compared to expected values obtained by randomization of the HLA haplotype, inherited from the father, over the existing maternal haplotype of the fetuses. A similar methodology was executed for analysis of the KIR/HLA-C data (n=309).ResultsIn uncomplicated pregnancies, the degree of maternal-fetal HLA matching was not different than expected-by-chance values. In preeclamptic pregnancies, the degree of maternal-fetal HLA matching was different in observed compared to expected-by-chance values (p=0.012). More specifically, the degree of maternal-fetal matching of HLA-C was higher in the actual preeclamptic pregnancies than was expected-by-chance (p=0.007). Preeclamptic pregnancies showed an overall tendency towards higher maternal-fetal HLA compatibility, for total HLA matches (p=0.021), HLA class I (p=0.038) and HLA-C (p=0.025) compared to uncomplicated pregnancies.ConclusionThe data suggest that there is no preferential selection of maternal-fetal HLA compatibility in uncomplicated pregnancies. In contrast, increased total HLA, HLA class I and, especially, HLA-C compatibility is associated with preeclampsia, suggestive for a role of HLA mismatches in immune regulation leading to uncomplicated pregnancy.

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IntroductionIn severe cases of COVID-19, late complications such as coagulopathy and organ injury are increasingly described. In milder cases of the disease, the exact time frame and causal path of late onset complications has not yet been determined. Although direct and indirect renal injury by SARS-CoV-2 has been confirmed, hemorrhagic renal infection or coagulative problems in the urinary tract have not yet been described.Case PresentationThis case report describes a 35-year-old female without relevant medical history who, five days after having recovered from an infection with SARS-CoV-2, had an unusual course of acute pyelonephritis of the right kidney and persistent fever under targeted antibiotic treatment. A hemorrhagic ureteral obstruction and severe swollen renal parenchyma preceded the onset of fever and was related to the developing pyelonephritis. Sudden thrombotic vascular occlusion in the right eye appeared during admission. Symmetrical paresthesia in de limbs in combination of severe lower back pain and gastro-intestinal manifestation was documented and not been explained despite of intensive investigation.ConclusionWe present the unusual combination of culture confirmed bacterial hemorrhagic pyelonephritis with a blood clot in the proximal right ureter, complicated by a retinal venous thrombosis, in a patient who had recovered from SARS-CoV-2-infection five days before presentation. The case is suspect of a COVID-19 related etiology.

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