Purpose In a multicenter randomized clinical trial we evaluated the safety and efficacy of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of reinfection in solid organ recipients with severe infections and secondary antibody deficiency. Methods Distribution: Heart 20, Lung 15, Kidney 5, Liver transplantation 4 were randomized. Patients with post transplant severe infections and secondary antibody deficiency (defined as IgG < 600 mg/dL) were included. IVIG protocol: Two doses of 15 grams (interval between doses 7-15 days) followed by another 3 doses of 20 grams (interval between doses 15-30 days) of a 5% IVIG product. 39 patients that completed the protocol were analysed [IVIG in combination with conventional antimicrobial therapy (n=21) versus conventional antimicrobial therapy alone (n=18)]. Specific antibodies were tested at inclusion in the clinical trial (V1) and 30-45 days after last IVIG dose (last-visit, V7) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution. Results The primary outcome measure (rate of reinfection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (28.6 vs 66.7%, chi-square test, p=0.017). Mean number of reinfections tended to be lower in IVIG group (0.47, interval 1-3, versus 0.89, interval 1-4, Mann-Whitney test, p=0.056). IVIG recipients tended to have lower IgG levels in V1 but disclosed significantly higher IgG concentrations at distinct visits during follow-up. Significantly higher levels of specific IgG anti-cytomegalovirus, IgG anti-clostridium difficile toxins A and B and IgG1 anti-tetanus toxoid antibodies was demonstrated at V7 in patients who received IVIG as compared with patient that were treated with antimicrobial therapy alone. A significant decrease of serum IL6 and BAFF levels (V1 versus V7) was demostrated in IVIG treated patients. IVIG infusions were well tolerated. Conclusion In a multicenter randomized clinical trial we have demonstrated that IVIG is associated with a lower rate of reinfection in solid organ transplantation with severe infection and secondary IgG hypogammaglobulinemia.

Purpose: The last decade has seen a considerable rise in ventricular assist device (VAD) support as bridge to heart transplant (HT) coupled with increasing transplantation for single ventricle congenital heart disease (SV CHD).Neurologic events (NE) are common in both patient groups.We sought to describe NE before and after HT in the modern era among children and young adults.Methods: We performed a single center retrospective review of patients who underwent HT between 1/2013 and 4/2020.NE included seizures, stroke, subdural hemorrhage (SDH) and posterior reversible encephalopathy syndrome (PRES).Clinical characteristics were compared between patients with and without post-HT NE.Results: Overall 163 patients met study criteria, of whom 54 (33%) had a pre-HT NE and 29 (18%) had at least one post-HT NE.Post-HT NE included seizures in 23/163 (14%), strokes in 10/163 (6%), SDH in 9/163 (6%), and PRES in 7/163 (4%).Median time from HT to first post-HT NE was 24 days (IQR 3, 277).Post-HT NE were associated with SDH (6/29 (21%) vs 9/134 (7%), p=0.03), pre-HT ICU admission (11/29 (38%) vs 21/ 134 (16%), p=0.009), and allograft ischemic time (250 min (IQR 221, 224) vs 223 min (IQR 189, 250), p=0.001), and not with pre-HT NE, SV CHD, or VAD support.ICU admission was an independent predictor of post-HT NE on multivariate analysis (hazard ratio 2.87 (CI 1.09, 7.62), p=0.03).Post-HT NE were associated with significantly decreased survival.Conclusion: Post-HT NE are common in children and young adults and occur early post-HT.They are associated with ICU status at time of HT, and not with SV CHD or pre-HT VAD support.Post-HT neurologic events portend a poor prognosis, with 50% mortality by 5 years.

Purpose Bacterial infections are the most frequent infectious complications after heart transplantation. IgA and IgM serological response to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) can be used to assess antibody function against T-cell independent type-2 antigens (anti-PPS). We evaluated if IgA and IgM anti-PPS titers after vaccination in a cohort of heart recipients were associated with the risk for development of bacterial infections. Methods A prospective follow-up study of 151 adult heart recipients (124 male, 27 female, mean age: 58 years) at a single center. The study population received one injection of PPSV23 before transplantation. Specific IgA and IgM anti-PPS were measured in pre and post vaccination sera before transplantation by ELISA (2-3 weeks interval between pre and post vaccination samples) and at distinct times after transplantation (day 7, 30, 90, 180). ELISA plate contained the 23 antigens of the pneumococcal vaccine. The prevalence of bacterial infections was registered during the first 6 months after transplantation. Results During follow-up 32 patients (21%) developed bacterial infectious complications that required IV drug therapy in hospital. Mean anti-PPS titers were significantly lower in transplanted patients who developed bacterial infections as compared with heart recipients who remained free of bacterial infections: after vaccination before transplantation (IgA anti-PPS, 12±10 vs 27±51 mg/dL, p=0.031), at day 7 after transplantation (IgA anti-PPS, 6±5 vs 13±12 mg/dL, p=0.01), at day 30 after transplantation (IgA anti-PPS, 6±5 vs 19±34 mg/dL, p=0.003 and IgM anti-PPS, 6±4 vs 14±19 mg/dL, p=0.002), at day 90 (IgA anti-PPS, 4±2 vs 17±10 mg/dL, p=0.003 and IgM anti-PPS, 7±4 vs 13±8 mg/dL, p=0.04) and at day 180 (IgA anti-PPS, 3±1 vs 15±9 mg/dL, p=0.003). Conclusion Low IgA and IgM anti-polysaccharide responses may predispose heart recipients to develop bacterial infections. IgA anti-PPS as a biomarker warrants validation in a multicenter study.

In a randomized clinical trial we have preliminarily demonstrated that IVIG is associated with reconstitution of distinct specific antibodies and with a lower rate of re-infection in solid organ transplantation with severe infection and secondary antibody deficiency.

Purpose The identification of pre-transplant biomarkers to assess the risk of post transplant infections in lung transplantation is of interest. The anti-inflammatory cytokine interleukin-10 (IL-10) was investigated in this study. Higher IL-10 plasma levels have been associated with prolonged CMV clearance in lung recipients. In other clinical setings higher IL-10 levels have been found to be a predictor of clinical outcome in sepsis. In this study we evaluated the relationship between pre-transplant IL-10 serum concentration and the development of infections occurring after lung transplantation. Methods In a prospective follow-up multicenter study, 87 patients in 5 centers were included to identify potential biomarkers of risk for development of post transplant infections. 82 patients were transplanted. 41 patients (50%) developed at least one infection episode that required intravenous drug therapy during the first 6 months after transplantation. Pre-transplant IL-10 was measured with an enzyme-linked immunosorbent assay in blood. IL-10 levels were then correlated with the prevalence of infections. Results The distribution of post transplant infections was as follows: bacterial (67,35%), fungal (20,41%), viral (10,20%). Patients who developed infections disclosed significantly higher levels of pre-transplant serum IL-10: 43,26 ± 39,55 pg/ml vs. 21,70 ± 23,34 pg/ml; p 29 pg/ml were at higher risk of having post transplant infections (Logistic regression relative hazard 3.64 (p= 0.021; 95% confidence interval: 1.28- 10.87). Conclusion We demostrated that in lung recipients with pre-transplant higher levels of serum IL-10, the prevalence of post-transplant infections was higher which suggest a potential role of individual anti-inflammatory responses in the predisposition to infection.

Purpose The IgG antibody response against polysaccharide microbial antigens is enriched for IgG2 antibodies, which possess characteristics that are likely to enhance opsonisation of these antigens. IgG2 molecules are more effective than other IgG subclasses in opsonising antigens with a high epitope density. Lower IgG2 concentration has been found to be a risk factor of death after community acquired pneumonia. Infection is still a major cause of death during the first year after heart transplantation. In this study we evaluated the prevalence of IgG2 insufficiency in heart recipients before transplantation and its relationship with the risk for development of severe deadly infections. Methods 119 patients evaluated in a single center were included. Prospective follow-up was performed to identify the clinical outcomes: early deadly infections during the first month and deadly infections during the follow-up after transplantation. In this study using the Binding Site nephelometry test, IgG2 insufficiency was defined as IgG2 levels below 2.72 mg/dL. Results In the pre-transplant evaluation 46 (38.7%) patients were found to have IgG2 insufficiency. Early deadly infections were more prevalent among patients with IgG2 insufficiency (RH 2.68, 95% CI 1.10-6.53, p=0.029). Use of mechanical ventilation, pre-transplant infections and pre transplant use of ventricular assist devices were risk factors of early deadly infections. In multivariate regression analysis IgG2 insufficiency remained in the model (RH 4.18, 95% CI 1.20-14.47, p=0.024). IgG2 insuficiency was also a risk factor of deadly infections (RH 4.27, 95% CI 1.37-13.26, p=0.012) and a risk factor of 1-year all-cause mortality (RH 2.68, 95% CI 1.10-6.53, p=0.029). Conclusion Pre-transplant IgG2 insufficiency is a risk factor of bad outcome after transplantation. This immunological biomarker warrants evaluation in a multicenter study. The IgG antibody response against polysaccharide microbial antigens is enriched for IgG2 antibodies, which possess characteristics that are likely to enhance opsonisation of these antigens. IgG2 molecules are more effective than other IgG subclasses in opsonising antigens with a high epitope density. Lower IgG2 concentration has been found to be a risk factor of death after community acquired pneumonia. Infection is still a major cause of death during the first year after heart transplantation. In this study we evaluated the prevalence of IgG2 insufficiency in heart recipients before transplantation and its relationship with the risk for development of severe deadly infections. 119 patients evaluated in a single center were included. Prospective follow-up was performed to identify the clinical outcomes: early deadly infections during the first month and deadly infections during the follow-up after transplantation. In this study using the Binding Site nephelometry test, IgG2 insufficiency was defined as IgG2 levels below 2.72 mg/dL. In the pre-transplant evaluation 46 (38.7%) patients were found to have IgG2 insufficiency. Early deadly infections were more prevalent among patients with IgG2 insufficiency (RH 2.68, 95% CI 1.10-6.53, p=0.029). Use of mechanical ventilation, pre-transplant infections and pre transplant use of ventricular assist devices were risk factors of early deadly infections. In multivariate regression analysis IgG2 insufficiency remained in the model (RH 4.18, 95% CI 1.20-14.47, p=0.024). IgG2 insuficiency was also a risk factor of deadly infections (RH 4.27, 95% CI 1.37-13.26, p=0.012) and a risk factor of 1-year all-cause mortality (RH 2.68, 95% CI 1.10-6.53, p=0.029). Pre-transplant IgG2 insufficiency is a risk factor of bad outcome after transplantation. This immunological biomarker warrants evaluation in a multicenter study.

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene. Previous epidemiological studies have presented evidence regarding associations between IL1RN polymorphisms and sepsis susceptibility. In the present study the potential role of IL-1RN genotypes was evaluated as a potential risk factor of severe infection in heart recipients.

Due to growing incidence of severe infections associated with secondary antibody deficiency (SAD), this risk factor is being explored as a potential new indication of intravenous immunoglobulin (IVIG) in settings such as solid organ transplantation, post-rituximab use in autoimmune diseases and after therapy of B-cell lymphomas. The clinical criteria for this IVIG indication is the presence of severe infections. The immunological criteria that is being explored by the European Medicines Agency is the presence of severe hypogammaglobulinemia (HGG: IgG below 400 mg/dL) with demonstration of failure to produce specific antibodies after vaccination. In the case of thoracic transplantation the majority of severe infections are concentrated during the first 6 months, a period in which vaccination is avoided in the majority of centers. Objective. To define the prevalence and components of severe SAD in thoracic transplantation.

The indication of induction immunosuppressive therapies in heart transplantation (HT) is still controversial. 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 is not a common practice but might provide useful information.

Acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV) continue to hinder the long-term success of heart transplantation (HT). However, we still lack reliable biomarkers to identify heart recipients at risk of humoral and cellular acute and chronic rejection. Changes in biomarker levels after HT can reflect various processes, such as inflammation, cardiomyocyte necrosis, heart function, fibrosis, and global cardiorenal risk. We aimed to assess the relationship between the levels of specific serum proteins and development of ACR and CAV in a retrospective case-control study performed in HT.

Acute allograft rejection is a problem in lung transplantation. More than a third of lung transplant recipients are treated for acute rejection in the first year after transplant. Growing evidence suggests that B cells may play a role in allograft rejection in solid organ transplantation. B cell activating factor, BAFF, plays a role in B cell survival, maturation and activation. To date, little is known of the role of BAFF in lung transplantation. We aimed to determine whether there was a correlation between BAFF concentration and acute rejection.

Background Autoantibodies, low complement levels and higher NK cell counts are present in a subset of women with recurrent pregnancy loss (RPL). The combination of these abnormalities might be a surrogate profile for the presence of a subclinical inflammatory or autoimmune condition. Objectives In a cohort of women with unexplained RPL we evaluated if an immunological profile combining innate and adaptive immunity mediators was associated with the presence of distinct clinical characteristics that are commonly observed in autoimmune diseases and if it was a risk factor for developing these diseases. In a small subset of women with the immunological profile we evaluated the activation status of CD4+ and CD8+ cells. Methods We evaluated 366 women with RPL defined as 2 or more pregnancy losses and 93 control women. We defined the immune profile as the presence of 2 or more of the following abnormalities: Peripheral blood NK cell percentages >15%, positive antiphospholipid antibodies, positive antinuclear antibodies, positive anti-thyroid antibodies, low complement C3 levels and low C4 complement levels. Evolution to autoimmune diseases was detected during follow-up. Lymphocyte subsets were evaluated by flow-cytometry. Statistics: Chi-square test. Logistic regression. Results The prevalence of women with 2 or more immunological abnormalities was 57 out of 366 women (15.6%) and was significantly higher than in control women. Demographic clinical characteristics were similar in women with 2 or more immunological abnormalities as compared with women with only one immunological alteration or no abnormalities. The presence of the immunological profile was significantly associated with the presence of the following clinical characteristics: Leucopenia (p=0.048), lymphopenia (p=0.007), livedo reticularis (p=0.01), cutaneous rash (p=0.009), and arthritis (p=0.001). During follow-up 17 patients (4.6%) developed an inflammatory or autoimmune disease that was not present at the time of the diagnose of RPL including SLE and lupus like disease. Women with the immunological profile were at higher risk for evolution into these diseases: OR 4.19, 95% confidence interval 1.52–11.51, p=0.0055. In 10 women with the immunological profile we observed significantly higher levels of CD4+DR+ and CD8+DR+ T-cells as compared with women without the immune profile. Conclusions A subgroup of women with unexplained RPL are at risk of developing clinical characteristics of an inflammatory or autoimmune disease. In this regard, the immunological evaluation of women with RPL might be necessary not only to identify a potential cause of abortion but also to identify women that could require a more careful clinical follow-up. Higher CD4+DR+ and CD8+DR+ T-cells might be a pathogenic pathway leading to development of autoimmune diseases in RPL women. References Viallard JF, Bloch-Michel C, Neau-Cransac M, Taupin JL, Garrigue S, Miossec V, Mercie P, Pellegrin JL, Moreau JF. HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus. Clin Exp Immunol. 2001;125(3):485–91. CD8+DR+ T-Cells and C3 Complement Serum Concentration as Potential Biomarkers in Thrombotic Antiphospholipid Syndrome. Sarmiento E, Dale J, Arraya M, Gallego A, Lanio N, Navarro J, Carbone J. Autoimmune Dis. 2014. Acknowledgements Research Funds. Fundacion Salud 2000. Madrid Spain. Disclosure of Interest None declared

New therapeutic approaches are needed to improve survival outcomes for patients with severe infections after solid organ transplantation (SOT). One such approach might be adjunctive treatment with intravenous immunoglobulin (IVIG) in patients with hypogammaglobulinemia. Antibody titers in IVIG products are considered as being critical for efficacy. In a substudy performed in a randomized multicenter clinical trial of IVIG in solid organ transplantation with hypogammaglobulinemia and severe infections, we aimed to demonstrate if IVIG conferred protection against distinct microorganisms.

Some heart recipients are more susceptible to earlier onset of severe infections after transplantation. In primary antibody deficiencies it has been suggested that switched memory B cells (SMB cells) can be used as a tool to identify patients at higher risk for development of infectious complications. The aim of this study was to evaluate in a cohort of heart recipients if the quantification of pre-transplant peripheral blood SMB cells was useful to identify those patients at higher risk for severe infections.

During the first year infection remains as a major problem after heart transplantation (HT). We aimed to assess an extended humoral immunity profile to be performed before transplantation as a potential tool to identify high risk of infection. In a prospective multicenter follow-up study (9 centers in Spain), we evaluated 290 patients at the time of inclusion in the waiting list. Laboratory tests: immunoglobulin levels (IgG, IgA, IgM), complement factors (C3 and C4) and IgG anti-CMV serology. These biomarkers are easily available in the routine laboratory facilities in transplant centers. The prevalence of infection during the first 6 months was registered. Infections were defined as severe infections requiring IV-antimicrobial therapy. During follow-up, 96 patients developed infections including severe bacterial infections, CMV disease and systemic fungal infections. The individual risk factors of overall infection (Logistic regression) were as follows: Serum IgG <850 mg/dL (relative hazard [RH], 1.88; 95% confidence interval [CI], 1.04-3.41; p=0.01), C3 <110 mg/dL (RH, 2.68; 95% CI, 1.46-4.92; p=0.0014) and negative IgG anti-CMV serology (RH, 2.75; 95% CI, 1.28-5.91; p=0.0093). An immunological score was created using hazard ratios to determine the number of points assigned to each of the individual risk factors and the sume was the score. In multivariate analysis an immunological score ≥3 was stronger as a risk factor of severe infections (RH, 5.61; 95% CI, 2.41-13.06; p=0.0001); specificity 94%. After adjustment by clinical risk factors the score remained as a significant risk factor for severe infection. A pre transplant immunological score combining IgG, C3 and CMV serology was useful for identifying heart recipients at risk of developing severe infections. Fund. Fondo de Investigación Sanitaria. Project FIS 11/01323, Spain.

Ventricular assist device (VAD) infections are difficult to manage. The potential role of the immunocompetence status on development of infections in heart recipients using VADs has been poorly investigated. We aimed to evaluate the relationship between humoral and cellular immunity abnormalities and development of severe infections in these patients. We performed a retrospective analysis of 25 VAD implantations as bridge to transplant or after transplant in heart recipients between 2003 and 2010 at our institution. Nine patients developed at least one episode of severe infection during the first 3 months after transplantation. Infections were defined as all episodes that required IV antimicrobial therapy. Catheter related infections and superficial surgical wound infections were not included as events. The immunocompetence protocol was performed at 7 days after transplantation including: IgG, IgG subclasses, distinct IgG specific antibodies, IgA, IgM, C3, C4, mannose binding lectins and CD3+, CD4+, CD8+, CD19+ and CD3-CD16+/CD56+ lymphocyte subsets. Patients who developed infections were found to have significantly lower levels of the following parameters as compared with heart recipients without infections: IgG (497 ± 145 vs 668 ± 168 mg/dL, 2-sided Student’s T-test, p=0.048); complement C3 (62 ± 26 vs 137 ± 30 mg/dL, p<0.001); complement C4 (13 ± 6 vs 24 ± 6 mg/dL, p=0.003); CD3+ T-cell absolute counts (265 ± 199 vs 610 ± 184 cells/uL, p=0.008) and of absolute counts of CD4+ T-cells (183 ± 97 vs 424 ± 123 cells/uL, p=0.004). Mannose binding lectin and factor B levels tended to be lower in patients who had infections (309 ± 361 vs 945 ± 702, p=0.14 and 22 ± 6 vs 32 ± 12 ng/mL, p=0.18, respectively). Specificities in ROC analysis were as follows: IgG<500 mg/dL 81%, C3<95 mg/dL 95%, C4<16 mg/dL 91%, CD4<300 cells/uL 98%. In this cohort of heart recipients using VADs, patients who developed severe infections were found to have significantly lower levels of distinct humoral and cellular immunity parameters early after transplantation. The potential role of these routine parameters as risk factors for development of infections should be evaluated in multicenter prospective studies.

Lower naive B-cells and higher memory class-switched B cells have been described in trasplant recipients with rejection. It has been suggested that naïve B-cells may disclose regulatory functions. Indeed, operational tolerance has been accounted by increased frequencies of transitional and naïve B-cells. In this study we performed an extended immunological analysis to assess the correlation between naïve B-cells and memory class-switched B cells in heart transplantation (HT) with and without acute cellular rejection (ACR). We analyzed 46 HT, 11 of whom developed at least one episode of treated ACR during the first year after HT (graded as ISHLT 1R or greater). Study times: At the time of inclusion in the waiting list, 7 days and 6 months after HT. 28 heart recipients with more than one-year after HT, 31 patients with open heart surgery without immune suppression and 33 healthy individuals were analyzed as control groups. Surgical controls were evaluated before surgery and one week after surgery. Naïve B-cells (CD19+CD27-IgM+IgD+) and memory class-switched B-cells (CD19+CD27+IgM-IgD-) were evaluated by 4-colour flow cytometry. A significative negative correlation was found between naïve B-cells and memory class-switched B-cells in healthy controls (Pearson correlation -0.72, p<0.001); in patients with more than one year after HT (-0.89, p<0.001), and in surgical controls at baseline and 7 days after surgery (-0.77, p<0.001 and -0.79, p<0.001, respectively). Baseline correlations between B-cell subsets in heart recipients without and with rejection were -0.80, p<0.001 and -0.78, p=0.013, respectively. At day 7 and 6-months after transplantation heart recipients without ACR maintained this correlation (-0.76, p<0.001 and -0.74, p<0.001) while patients with ACR loss the correlation between naïve B-cells and memory class-switched B-cells (-0.49, p=0.19 and -0.28, p=0.41, respectively). Lower levels of naïve-B cells at one-week after transplantation (<58%) were associated with a higher rate of ACR (Log rank 7.80, p=0.005). A loss of correlation between naïve B-cells and memory class-switched B cells is observed early after transplantation in patients who later develop ACR. These results highlight the hypothesis of a potential role of B-cells in the pathogenesis of ACR. Limitation. Study sample.

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. (C) 2017 International Society for Heart and Lung Transplantation. All rights reserved.

To investigate whether Toll-like receptor (TLR) expression on distinct leukocyte subsets and the human leukocyte antigen-DR (HLA-DR) expression on peripheral monocytes could be utilized as biomarkers of risk for severe infections after heart transplantation. 41 patients diagnosed with terminal heart disease and who were admitted into Gregorio Marañon Hospital for heart transplant evaluation were included. We have evaluated the expression of TLR2 and TLR4 in monocytes, plasmacytoid dendritic cells and myeloid dendritic cells and HLA-DR/CD38 expression on peripheral monocytes at the time of pre-transplant evaluation and on the 7th day after transplantation with flow cytometry analysis to determine whether a prediction could be made in regards to development of a severe infection. There were 20 patients with severe infectious complications. Before heart transplantation TLR2 expression on plasmacytoid dendritic cells was significantly higher in heart recipients who developed infections (MFI ratio 1.24 vs 1.007, P=0.02). On 7th day after transplantation, HLA-DR+CD38+ expression on monocytes in the infected patients was lower than those in the noninfected patients (80 vs 89%, P = 0.046). The area under the ROC curve (AUC) was 0.837 (95%CI: 0.685-0.989, P = 0.001) for CD14+DR+CD38+ percentage to predict severe infection. The cut-off value of prediction of severe infection was 85% with a specificity of 89%. The results indicate that TLR2 expression in plasmacytoid dendritic cells is up-regulated before transplantation in patients who later develop severe infections including opportunistic pathogens in the post-transplant period. We suggest that modulation of TLRs expression might represent a mechanism that promotes a tendency towards bad control of infections when the immunosuppressive status of transplantation is present. On the other hand, as it has been suggested in other clinical settings, the HLA-DR expression on monocytes may be a biomarker for an early prediction of severe infections. Limitations. Small sample.