Plasma cell biology: Foundations for targeted therapeutic development in transplantation

Abstract

Solid organ transplantation is a life‐saving procedure for patients with end‐stage organ disease. Over the past 70 years, tremendous progress has been made in solid organ transplantation, particularly in T‐cell‐targeted immunosuppression and organ allocation systems. However, humoral alloimmune responses remain a major challenge to progress. Patients with preexisting antibodies to human leukocyte antigen (HLA) are at significant disadvantages in regard to receiving a well‐matched organ, moreover, those who develop anti‐HLA antibodies after transplantation face a significant foreshortening of renal allograft survival. Historical therapies to desensitize patients prior to transplantation or to treat posttransplant AMR have had limited effectiveness, likely because they do not significantly reduce antibody levels, as plasma cells, the source of antibody production, remain largely unaffected. Herein, we will discuss the significance of plasma cells in transplantation, aspects of their biology as potential therapeutic targets, clinical challenges in developing strategies to target plasma cells in transplantation, and lastly, novel approaches that have potential to advance the field.

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

“…GO-term analysis based on the top 30 differentially expressed genes of PCs from both conditions revealed an overrepresentation of biological pathways associated with intense protein processing and B-cell receptor signaling pathway in PCs from ISGS (Figure 2C) Subsetting of the PC cluster uncovered 6 transcriptionally distinguishable PC-subtypes (PC1-PC6) in ISGS (Figure 2D). A more precise annotation of the detected subclusters according to previously described PC subtypes was not feasible (Figures S3) (38, 39). PC2 appeared to constitute the predominant PC type in healthy tissue (Figure 2D).…”

“…Subsetting of the PC cluster uncovered 6 transcriptionally distinguishable PC-subtypes (PC1-PC6) in ISGS (Figure 2D). A more precise annotation of the detected subclusters according to previously described PC subtypes was not feasible (Figures S3) (38,39). PC2 appeared to constitute the predominant PC type in healthy tissue (Figure 2D).…”

Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation

“…Studies on the mTORi effects on B cells, particularly plasmablasts and plasma B cells, are limited. 25 Hence, this might be important to better understand the production and prevention of DSAs after kidney transplantation upon mTORi-based immunosuppression. [26][27][28] Notably, p70S6K phosphorylation in plasmablasts was significantly stronger in the rejection group compared with the nonrejection group (Figure S4, SDC, http://links.lww.com/TXD/ A672).…”

Whole-eye transplantation: Current challenges and future perspectives

“…A significant effort has been directed towards minimizing immunosuppressive regimens by employing lower dosages and reducing the number of medications; however, this has been associated with an increased risk of allograft rejection. Novel immunomodulatory agents, such as anti-T-cell targeting molecules[ 100 ], interleukin-2 receptor antibodies[ 101 ], and monoclonal antibodies like alemtuzumab and rituximab[ 102 , 103 ], have demonstrated promising outcomes in this context. The heterogeneity of ocular tissue renders eye transplantation highly immunogenic, despite its immune-privileged characteristic, and challenging to manage without robust immune suppression, which inevitably carries its own set of side effects[ 102 , 104 , 105 ].…”