A transitional B-cell cytokine biomarker for risk stratifying renal transplant patients with borderline rejection.

Borderline allograft rejection can promote acute rejection and graft loss in some, but not all, patients. In this issue, Cherukuri et al. use a novel test based on peripheral blood transitional T1 B cells producing interleukin-10 and tumor necrosis factor-α, which identifies patients at high risk for poor outcomes. The potential mechanisms by which transitional T1 B cells might modulate alloreactivity need exploration, but following appropriate validation, this biomarker could risk stratify patients in need of early intervention.

Regulation of T- and B-cell interactions determines the clinical phenotype associated with donor-specific antibodies.

The cellular mechanisms that regulate donor-specific antibody formation and antibody-mediated rejection remain unknown. In this issue, Louis et al. report that specific T-regulatory cell and B-regulatory transitional cell subsets are concomitantly diminished in patients with donor-specific antibody and consequent antibody-mediated rejection and advance alterations in specific cytokines and costimulatory molecules as important mechanisms by which these cells may suppress donor-specific antibody formation and, independently, progression to antibody-mediated rejection.

Potential Application of T-Follicular Regulatory Cell Therapy in Transplantation.

Regulatory T cells (Tregs) constitute a small proportion of circulating CD4+ T cells that function to maintain homeostasis and prevent autoimmunity. In light of their powerful immunosuppressive and tolerance-promoting properties, Tregs have become an interesting potential candidate for therapeutic use in conditions such as solid organ transplant or to treat autoimmune and inflammatory conditions. Clinical studies have demonstrated the safety of polyclonally expanded Tregs in graft-versus-host disease, type 1 diabetes, and more recently in renal and liver transplantation. However, Tregs are heterogenous. Recent insights indicate that only a small proportion of Tregs, called T follicular regulatory cells (Tfr) regulate interactions between B cells and T follicular helper (Tfh) cells within the germinal center. Tfr have been mainly described in mouse models due to the challenges of sampling secondary lymphoid organs in humans. However, emerging human studies, characterize Tfr as being CD4+CD25+FOXP3+CXCR5+ cells with different levels of PD-1 and ICOS expression depending on their localization, in the blood or the germinal center. The exact role they play in transplantation remains to be elucidated. However, given the potential ability of these cells to modulate antibody responses to allo-antigens, there is great interest in exploring translational applications in situations where B cell responses need to be regulated. Here, we review the current knowledge of Tfr and the role they play focusing on human diseases and transplantation. We also discuss the potential future applications of Tfr therapy in transplantation and examine the evidence for a role of Tfr in antibody production, acute and chronic rejection and tertiary lymphoid organs. Furthermore, the potential impact of immunosuppression on Tfr will be explored. Based on preclinical research, we will analyse the rationale of Tfr therapy in solid organ transplantation and summarize the different challenges to be overcome before Tfr therapy can be implemented into clinical practice.

How effective is bipolar radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether, in patients undergoing cardiac surgery, concomitant bipolar radiofrequency ablation had an acceptable success rate to justify the additional procedure. Altogether 263 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The consensus in the literature was that bipolar radiofrequency ablation was highly successful in restoring sinus rhythm. One meta-analysis of six non-randomized studies demonstrated that 76% of patients were in sinus rhythm compared with 16% in atrial fibrillation 3 months postoperatively. One randomized controlled trial found that the sinus rhythm conversion rate for any maze procedure was highly significant compared with the control group (P = 0.001). Another found that Cardioblate radiofrequency ablation was significantly better at restoring sinus rhythm at 1 year (75 vs 39% control, P = 0.019). Prospective studies showed a similar rate of sinus rhythm return at 1 year (89%). Notably some studies demonstrated a significant reduction in the New York Heart Association class when sinus rhythm was restored compared with those remaining in atrial fibrillation (P < 0.0001), demonstrating the value of this procedure beyond simply restoring sinus rhythm. In another study, the investigators found that both ablation and total procedure times were shorter with bipolar compared with monopolar ablation. These authors strongly recommend bipolar radiofrequency ablation due to a shorter procedure time, ability to avoid performing a standard left atriotomy and a greater guarantee of transmurality. With the current limited evidence, we conclude that bipolar radiofrequency ablation has a higher success rate in restoring sinus rhythm as an adjunct to cardiac surgery compared with no ablation for at least 1 year. The procedure had a high survival rate. There is randomized evidence to suggest the superiority of bipolar radiofrequency ablation over microwave ablation but limited evidence to suggest the superiority of bipolar over unipolar radiofrequency ablation. Factors found to be accurate predictors of ablation failure include a larger preoperative atrial diameter, permanent vs paroxysmal atrial fibrillation and longer duration of atrial fibrillation.