ABSTRACT
Background: Primary membranous nephropathy (PMN) is an autoimmune kidney disease. Despite the identification of certain autoantigens, the etiology and pathophysiology of PMN are still largely unknown. Methods: Five patients with biopsy-proven PMN were enrolled in this study. Their blood, kidney and urine samples were collected respectively to profile cellular, molecular and immunological alterations by using single-cell RNA sequencing (scRNA-seq). Experimental verifications were also implemented in kidney tissue. Results: In the peripheral blood mononuclear cell (PBMC) samples, portions of B cells and plasma cells were increased in PMN patients. Cell-cell communication analysis suggests that APRIL (a proliferation-inducing ligand from B cells) might be a potential molecule that regulates the activity of plasma cells. In the kidney samples, scRNA-seq analysis showed that the infiltration of T cells, as well as the myeloid cells, appears abundant compared with healthy controls, suggesting that immune cells are actively recruited to kidney. Furthermore, we observed an enhanced interaction between inflammatory cells and podocytes, which might contribute to kidney injury. Accordingly, scRNA-seq analysis of urinary samples is partially reminiscent of the kidney cell landscape, especially T cells and myeloid cells, suggesting monitoring urinary samples is a promising method to monitor PMN development. Additionally, integrative analysis across the blood, kidney and urine identified LTB, HERP1, ANXA1, IL1RN and ICAM1 as common regulators of PMN. Finally, immune repertoire in PBMC also showed an elevated diversity of clonal type, implying the existence of autoreactive T-cell receptor/B-cell receptor. Conclusion: Our study comprehensively profiled the transcriptomic landscapes of blood, kidney and urine in patients with PMN using scRNA-seq. We depicted the alterations including cell compositions and cell-cell communication in PMN. These results offer important clues with regard to the diagnosis and pathogenesis of PMN and potential intervention of PMN progression.
ABSTRACT
Lung cancer is a common malignant tumor in clinic. Morbidity and mortality are the first place in cancer, which seriously threaten the health of human beings. Due to the lack of effective and specific screening methods, most patients were found already at an advanced stage, and often combined with bone, brain, liver, adrenal and other parts of the metastasis. Symptoms of patient resulted from the primary tumor, metastatic spread, or paraneoplastic syndrome commonly cause the medical attention. For the syndrome related to the distant metastatic spread as the first manifestation, diagnosis would be a challenge. Retinal metastasis is very rare as the first symptom of squamous cell carcinoma of the lung. This paper reviewed a case, in which a patient developed the retinal metastasis as the inital presentation. After systemic evaluation, our patient was managed in multidisciplinary treatments, including surgery and chemotherapy. Now, the patient has a good short-term prognosis and is still in fellow-up condition. Later, we summarized the characteristics of the diagnosis and treatment of this case and provided experience for clinicians. At the same time, reviewing the relevant literature on tumor metastasis provides a window for our understanding of the rare manifestations of lung cancer.
