L. Calahorra

Alterations of naïve and memory B‐cell subsets are associated with risk of rejection and infection in heart recipients

Rejection and infection are relevant causes of mortality in heart recipients. We evaluated the kinetics of the maturation status of B lymphocytes and its relationship with acute cellular rejection and severe infection in heart recipients. We analyzed B‐cell subsets using 4‐color flow cytometry in a prospective follow‐up study of 46 heart recipients. Lymphocyte subsets were evaluated at specific times before and up to 1 year after transplantation. Higher percentages of pretransplant class‐switched memory B cells (CD19+CD27+IgM‐IgD‐ >14%) were associated with a 74% decrease in the risk of severe infection [Cox regression relative hazard (RH) 0.26, 95% confidence interval (CI), 0.07–0.86; P = 0.027]. Patients with higher percentages of naïve B cells at day 7 after transplantation (CD19+CD27‐IgM+IgD+ >58%) had a 91% decrease in the risk of developing acute cellular rejection (RH 0.09; 95% CI, 0.01–0.80; P = 0.02). Patients with infections showed a strong negative correlation between baseline serum B‐cell–activating factor (BAFF) concentration and absolute counts of memory class‐switched B cells (R = −0.81, P = 0.01). The evaluation of the immunophenotypic maturation status of B lymphocytes could prove to be a useful marker for identifying patients at risk of developing rejection or infection after heart transplantation.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

BACKGROUND New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post‐transplant IgG HGG.

Potential role of serum BAFF as a biomarker in HIV infection

Abstract We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations (> 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p = 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.

Immune Monitoring of Regulatory CD4 T Cells in Heart Recipients Using One-Single Dose Versus Two-Dose Basiliximab Induction

Background The use of induction immunosuppressive therapies in heart transplantation (HT) is still controversial. Delay in the initiation and reduced calcineurin inhibitor dose, due to renal failure and other settings are used as potential indications to induction use in some centers. On the other hand minimization of doses of monoclonal antibodies for induction therapy is indicated in some clinical settings such as high infection risk. Immunemonitoring of lymphocyte subsets after induction therapy might provide useful information. Methods In a retrospective single center analysis of data prospectively collected, a comparative analysis of the kinetics of lymphocyte subsets was performed in patients using the recommended two doses [2D] of anti-IL2R-alpha monoclonal antibodies (Basiliximab, 20 mg, n=18) versus a single dose (1D, n=32). This was a non interventional study, single dose was indicated in specific clinical settings. We analysed the kinetics of regulatory CD4 T cells during the first 6 months after transplantation. Assessment points were pre-HT, day [d] 7, d15, d30, d60, d90 and d180. Maintenance immunosuppression included steroids, tacrolimus and mycophenolate mofetil in a similar way in both groups. Percentages and total counts of lymphocyte subsets were studied by flow-cytometry. Results Baseline (pre-HT) percentages were similar in both groups (5.45±2.48 vs 5.36±3.31%, p=0.93). In 2D group, a decrease of CD4+CD25+CD127low regulatory cells was observed as compared with pre-transplant values between day 7 and 60; while in 1D patients there were not significant differences. Lower levels of regulatory CD4+ cells were observed up to d30 in 2D patients as compared with 1D patients: d7 2.52±2.62 vs 4.76±3.90%, p=0.046; d14 2.75±2.55 vs 5.08±5.17%, p=0.074 and d30 2.96±2.69 vs 5.61±3.78%, p=0.014. During the 6 months follow up there was no significant difference in the prevalence of acute cellular rejection in both groups. Conclusion In a 6 month post transplant immunemonitoring follow-up study of a single cohort, one-dose of Basiliximab maintained higher levels of regulatory cells compared to a conventional 2-dose regimen. Since CD4 regulatory cells are considered to have an important role against allograft rejection, this information should be taken into account. The potential role of this cellular immune monitoring to assist in clinical decision making should be further explored in future studies. Fondo de Investigación Sanitaria. Project FIS 1501472. With participation of FEDER funds. A way of making Europe.