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Background: Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection., Methods: We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies., Results: Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns., Conclusions: Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity- and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Aims: Recent studies in patients with dilated cardiomyopathy (DCM) have detected the genome of Borrelia burgdorferi sensu lato (BBSL) in endomyocardial biopsy (EMB) specimens using a qualitative polymerase chain reaction (PCR), suggesting a causal link between Lyme disease and DCM in areas in which Lyme disease is endemic. We aimed to study this relationship using a comprehensive molecular analysis detecting BBSL in EMB samples., Methods and Results: We performed a comprehensive histopathological, immunohistochemical, ultrastructural, and molecular analysis targeting cardiotropic viruses and BBSL in EMB specimens of 41 individuals with recent-onset DCM and 15 controls with end-stage coronary artery disease. Specifically, quantitative PCR and electron microscopy of EMB specimens were employed. In addition, autoantibodies and manifestation of autoimmune diseases were evaluated in both groups. Individuals with recent-onset DCM presented more frequently with myocardial BBSL persistence as compared with the control group (24% vs. 0%, P = 0.035). In contrast, the prevalence of parvovirus B19 and cytomegalovirus was similar in both groups. Sequence analysis of borrelial DNA revealed the following genospecies: Borrelia burgdorferi sensu stricto in three patients (30%), Borrelia afzelii in two patients (20%), and Borrelia garinii in four patients (40%), the results being inconclusive in one case. BBSL-positive DCM patients had a higher prevalence of organ-specific autoimmune diseases in comparison with the remaining DCM patients (50% vs. 16%, P = 0.030)., Conclusion: Myocardial persistence of BBSL may be involved in the pathophysiology of DCM in individuals living in areas in which Lyme disease is endemic.