Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(IV)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4+ T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration.

Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.

Background: Previous studies on coronavirus disease 2019 have focused on populations with normal immunity, but lack data on immunocompromised populations. Objective: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. Design, setting, and participants: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. Intervention: Immunosuppressant reduction and low-dose methylprednisolone therapy. Outcome measurements and statistical analysis: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. Results and limitations: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 AE 9.3 vs 12.2 AE 4.6 d in the control group) and a longer course of illness (35.3 AE 8.3 vs 18.8 AE 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. Conclusions: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. Patient summary: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.

Highlights d Mitochondria-located circRNA SCAR inhibits mROS output and fibroblast activation d circRNA SCAR shuts down mPTP by binding to ATP5B d Lipid-induced ER stress impairs PGC-1a-mediated circRNA SCAR expression d Mitochondria-specific delivery of circRNA SCAR alleviates metaflammation in vivo

Reports have associated non‐HLA antibodies, specifically those against angiotensin II type‐1 receptor (AT1R), with antibody‐mediated kidney graft rejection. However, association of anti‐AT1R with graft failure had not been demonstrated. We tested anti‐AT1R and donor‐specific HLA antibodies (DSA) in pre‐ and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy‐proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG's rate of anti‐AT1R was significantly higher than the CG's (18% vs. 6%, p < 0.001). Moreover, 79% of ABG patients with anti‐AT1R lost their grafts (vs. 0%, CG), anti‐AT1R levels in 58% of those failed grafts increasing posttransplant. With anti‐AT1R detectable before DSA, time to graft failure was 31 months—but 63 months with DSA detectable before anti‐AT1R. Patients with both anti‐AT1R and DSA had lower graft survival than those with DSA alone (log‐rank p = 0.007). Multivariate analysis showed that de novo anti‐AT1R was an independent predictor of graft failure in the ABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti‐AT1R with graft failure. Further study is needed to establish causality between anti‐AT1R and graft failure and, thus, the importance of routine anti‐AT1R monitoring and therapeutic targeting.