Javier Carbone, Spain
Hospital General Universitario Gregorio Marañon ImmunologyPresenter of 5 Presentations
IGG2 INSUFFICIENCY BEFORE HEART TRANSPLANTATION: A NEW WAY OF EVALUATING RISK OF EARLY DEADLY INFECTIONS
Abstract
Background and Aims
The IgG antibody response against polysaccharide microbial antigens is enriched for IgG2 antibodies. Lower IgG2 concentration has been found to be a risk factor of death after community acquired pneumonia. Infection is a major cause of death during the first year after heart transplantation. We evaluated the prevalence of IgG2 insufficiency in heart recipients before transplantation and its relationship with the risk for development of severe early deadly infections.
Methods
119 patients evaluated in a single center were included. IgG2 assessment was performed at the time of inclusion in waiting list. Prospective follow-up was performed to identify early deadly infections during the first month after transplantation (n=11, mainly bacterial infections). Definitions: IgG2 deficiency, IgG2 <115 mg/dL; IgG2 insufficiency, IgG2 115-272 mg/dL.
Results
Forty-six (38.7%) patients disclosed 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). IgG anti-pneumococcal polysaccharide antibody levels were significantly lower in patients with IgG2 insufficiency before transplantation, at day 7 and day 30 after transplantation.
Conclusions
Pre-transplant IgG2 insufficiency is a risk factor of early deadly infection after heart transplantation. This new immunological definition warrants evaluation in a multicenter study.
COMPLEX SECONDARY IMMUNODEFICIENCY AFTER HEART TRANSPLANTATION
Abstract
Background and Aims
Infection is the first cause of death during the first year after heart transplantation according to the registry of the international society for heart and lung transplantation (2018). A complex secondary immunodeficiency (CSID) may affect a small number of heart recipients after transplantation and predispose them to severe or recurrent infections. We aimed to analyze the prevalence of this immunological complication in a cohort of heart recipients performed in a single center.
Methods
Prospective cohort follow-up. The CSID was defined as severe or recurrent infection requiring hospitalization including more than one type of microorganisms (i.e. bacterial + invasive fungal or bacterial + CMV disease) persisting after 6 months. Immunoglobulins, IgG subclasses, specific antibodies, C3, C4 and MBL complement factors and lymphocyte subsets were performed at 30 days after transplantation to define the combined secondary immunodeficiency status. A follow-up of 12 months was required to recruit patients.
Results
200 heart transplant recipients were evaluated. A total of 12 (6%) patients were found to have severe or recurrent infections persisting more than 6 months. IgG, IgA, IgM, IgG1, IgG2, anti-pneumococcal polysacharide antibody, anti-CMV antibody levels, CD3, CD4 and CD8 cells/uL were lower in these patients as compared with the rest of the cohort. In multivariate regression models IgG levels remained as the most strong predictor.
Conclusions
A CSID status including humoral and cellular immunity parameters was demonstrated in a small group of heart transplant recipients. A continuous highly specialized immunological monitoring is warranted after transplantation to detect this severe complex clinical setting.
MANNOSE-BINDING LECTIN GENOTYPES: A LINK BETWEEN PRIMARY IMMUNODEFICIENCY AND RISK OF CMV INFECTION IN HEART RECIPIENTS
Abstract
Background and Aims
Gene polymorphisms leading to lower serum levels of MBL, have been associated with an increased risk of infection. This study evaluates for the first time the correlation between functionally relevant MBL2 gene polymorphisms and serum MBL concentration in a cohort of heart recipients and risk of development of CMV infection after transplantation.
Methods
160 adult heart recipients were evaluated. Universal prophylaxis with gancyclovir was administered. CMV antigenemia and viral load were prospectively evaluated at distinct times after transplantation during the first year. Genotyping of MBL was done by a polymerase chain reaction/sequence-based typing technique. MBL serum concentration was evaluated by ELISA.
Results
During follow-up 30 patients (18.8%) developed CMV infection. Frequencies of the MBL genotypes in our patients was similar than that described in Spanish population. There was a good correlation between the MBL genotype and pre transplant serum concentrations of MBL. Patients with low and intermediate expressing MBL genotype were at higher risk of developing CMV infection during the first year after transplantation as compared with patients with the high-expressing genotype (RH 3.02, 95% CI 1.24-7.34, p=0.0146). After transplantation, patients with CMV infections showed significantly lower serum levels of MBL at day 30 as compared with recipients who did not developed CMV infection (559±443 vs 1233±920 ng/mL, p<0.001; T-2-tailed test). Pre-transplant and day 7 serum MBL tended to be lower in heart recipients who developed CMV infection.
Conclusions
Under the immunosuppressive clinical setting of heart transplantation MBL genotype and MBL serum levels were associated with high risk for development of CMV infection.
AN IMMUNOLOGICAL PROFILE OF SECONDARY IMMUNODEFICIENCY IS ASSOCIATED WITH MALIGNANCY RISK IN HEART TRANSPLANTATION
Abstract
Background and Aims
Malignancy is still a relevant barrier to long term survival after heart transplantation. Immune monitoring of basic components of the immune response could be a useful tool to identify the risk for development of malignancy. We aimed to identify immunological biomarkers that could be associated with risk of malignancy.
Methods
In a prospective follow-up study 265 patients were evaluated in a single center. Mean age was 66,48 years (women 13,04%, men 86,96%). During a long-term follow-up, 69 patients developed at least one new malignancy after heart transplantation. Mean time from transplantation to diagnosis of post transplant malignancy was 4,71 years. A total of 122 malignancies were diagnosed: epithelial (35,2%), mucose (24,6%), metastasis (8,2%). Immunological biomarkers were evaluated at the time of inclusion in waiting list and at 7 and 30 days after heart tranplantation.
Results
One-week after transplantation lower B-cell percentages (<3,13%) and lower B-cell absolute counts (<73,5 cells/uL) were risk factors for development of malignancy. Seven days after-transplantation, patients with IgG hypogammaglobulinemia (IgG<477 mg/dL, p=0,019), absolute NK-cell counts (<72,5/uL, p=0,004) and absolute T CD3+ counts (<208,50/uL) were at higher risk of having metastasis after diagnosis of malignancy during follow-up. Clinical risk factors of malignancy were age> 66 years; smoke; ischemia, chronic inflammatory conditions and infections. Low B-cell counts at 7 days (LB <73,5 cell/uL, OR 6.19, 95% CI 2,25-17,07, p<0,001) were significantly associated with malignancy risk after adjustment by clinical variables.
Conclusions
A profile of distinct immunological abnormalities is associated with a high risk for developing malignancy and metastasis after heart transplantation.
IVIG IS ASSOCIATED WITH LOWER RATES OF RE-INFECTION IN SOLID ORGAN RECIPIENTS WITH INFECTION AND SECONDARY ANTIBODY DEFICIENCY: PRELIMINARY RESULTS OF A RANDOMIZED CLINICAL TRIAL
Abstract
Background and Aims
In a multicenter randomized clinical trial we evaluated the efficacy of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of re-infection in solid organ recipients with severe infections and secondary antibody deficiency.
Methods
Distribution: Heart 19, Lung 9, Kidney 5, Liver transplantation 3. Patients with post transplant severe infections and secondary antibody deficiency (IgG levels < 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. 36 patients were randomized to receive IVIG in combination with conventional antimicrobial therapy (n=17) or conventional antimicrobial therapy alone (n=19). Specific antibodies were tested at inclusion in the clinical trial and 30-45 days after last IVIG dose (last-visit) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution.
Results
The primary outcome measure (rate of re-infection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (37.5 vs 76.5%, chi-square test, p=0.024). Time to reach normal IgG (IgG > 750 mg/dL) was shorter in IVIG group (55±44 vs 93±42 days, p=0.06). Significantly higher levels of specific anti-cytomegalovirus, anti-clostridium difficile toxins A and B was demonstrated at last-visit in patients who received IVIG as compared with patient that were treated with antimicrobial therapy alone.
Conclusions
In a multicenter randomized clinical trial we have preliminarily demonstrated that IVIG is associated with a lower rate of re-infection in solid organ transplantation with severe infection and secondary antibody deficiency.