Anti-Pdcd1 Monoclonal antibody, clone SNQ2-40 [PerCP-eFluor® 710]

We report the impact of anti-urothelial autoantibody (AUAb) on urinary bladder phenotype in BALB/c mice deficient of the Fc gamma RIIb and PD-1. AUAb was present in serum samples from approximately half of the double-knockout (DKO) mice, as detected by immunofluorescence and immunoblots for urothelial proteins including uroplakin IIIa. The AUAb-positive DKO mice showed degeneration of urothelial plaque and umbrella cells, along with infiltration of inflammatory cells in the suburothelial layer. TNF alpha and IL-1 beta were upregulated in the bladder and the urine of AUAb-positive DKO mice. Voiding behavior of mice was analyzed by the Voided Stain on Paper method. 10-week-old and older AUAb-positive DKO mice voided significantly less urine per void than did wild type (WT) mice. Furthermore, administration of the AUAb-containing serum to WT mice significantly reduced their urine volume per void. In summary, this report presents a novel comprehensive mouse model of autoimmune cystitis.

In current molecular medicine, next-generation sequencing (NGS) for transcript variant detection and multivariable analyses are valid methods for evaluating gene expression, cancer mechanisms, and prognoses of patients. We conducted RNA-sequencing on samples from patients with primary central nervous system lymphoma (PCNSL) using NGS and performed multivariable analysis on gene expression data and correlations focused on Th-1/Th-2 helper T cell balance and immune checkpoint to identify diagnosis/prognosis markers and cancer immune pathways in PCNSL. We selected 84 transcript variants to limit the analysis range for Th-1/Th-2 balance and stimulatory and inhibitory checkpoints in 31 PCNSLs. Of these, 21 highly-expressed transcript variants were composed of the formulas for prognoses based on Th-1/Th-2 status and checkpoint activities. Using formulas, Th-1(low), Th-2(high), and stimulatory checkpoint(high) resulted in poor prognoses. Further, Th-1(high)Th-2(low) was associated with good prognoses. On the other hand, CD40-001(high) and CD70-001(high) as stimulatory genes, and LAG3-001(high), PDCD1 (PD-1)-001/002/003(high), and PDCD1LG2 (PD-L2)-201(low) as inhibitory genes were associated with poor prognoses. Interestingly, Th-1(high)Th-2(low) and Th-1(low)Th-2(high) were correlated with stimulatory checkpoint(low) as CD70-001(low) and inhibitory checkpointlow as HAVCR2 (TIM-3)-001(low) and PDCD1LG2-001/201(low), respectively. Focused on the inhibitory checkpoint, specific variants of CD274 (PD-L1)-001 and PDCD1-002 served severe hazard ratios. In particular, PDCD1-002(high) by a cut off score was associated with poor prognoses, in addition to PDCD1-001/003(high), PDCD1LG2-201(low), and LAG3-001(high). These results mainly suggest that expression of transcript variants of PDCD1 and PDCD1LG2 on the Th-1/Th-2 balance enable prognostic prediction in PCNSL. This study provides insights for development of molecular target therapies and identification of diagnosis/prognosis markers in PCNSL.