Correlation of Fc Receptor Polymorphisms with Pneumococcal Antibodies in Vaccinated Kidney Transplant Recipients.

Several polymorphisms within Fc receptors (FCR) have been described, some of which correlate with allograft function. In the current study, we determined three Fcγ receptor and five Fcα receptor dimorphisms in 47 kidney transplant recipients who had been vaccinated against Streptococcus pneumoniae. We analyzed if FCR genotypes correlated with pneumococcal antibodies and their serotype-specific opsonophagocytic function, tested prior to and at months 1 and 12 post-vaccination. In parallel, we assessed antibodies against HLA and MICA and determined kidney function. We observed that IgG2 antibodies against pneumococci at months 1 and 12 after vaccination and IgA antibodies at month 1 differed significantly between the carriers of the three genotypes of FCGR3A rs396991 (V158F, p = 0.02; 0.04 and 0.009, respectively). Moreover, the genotype of FCGR3A correlated with serotype-specific opsonophagocytic function, reaching statistical significance (p < 0.05) at month 1 for 9/13 serotypes and at month 12 for 6/13 serotypes. Heterozygotes for FCGR3A had the lowest antibody response after pneumococcal vaccination. On the contrary, heterozygotes tended to have more antibodies against HLA class I and impaired kidney function. Taken together, our current data indicate that heterozygosity for FCGR3A may be unfavorable in kidney transplant recipients.

Humoral response to a 13-valent pneumococcal conjugate vaccine in kidney transplant recipients.

BACKGROUND: Vaccination against S. pneumoniae is recommended by national guidelines. Moderate immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) has been reported in adult kidney transplant recipients (KTR). This study further defines the immunogenicity of PCV13 in this cohort. METHODS: 49 KTR were immunized with PCV13. A validated opsonophagocytic killing assay (OPA), a global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG, IgG2, IgM and IgA ELISA, and - for selected patients - a serotype specific anti-PCP WHO reference ELISA were performed pre-vaccination and at month 1 and 12 post-vaccination. RESULTS: Geometric mean OPA titers increased significantly for 13/13 serotypes at month 1 and for 10/13 serotypes at month 12 post-vaccination. Vaccine response defined as an OPA titer ≥1:8 was reached in 9/13 serotypes (median). 53% reached the vaccine response criteria at month 1 and 45% at month 12. At month 1 after vaccination, the median OPA titer in an age-group matched healthy reference population was 5- to 10-fold higher than in KTR. OPA titers correlated strongly with results to the global and serotype specific anti-PCP IgG ELISA. Lower OPA titers significantly (p < 0.05) correlated with albuminuria, an interval between vaccination and transplantation <12 months, age and treatment with mycophenolate mofetil. Global IgG, IgG2, IgM and IgA, as well as serotype specific anti-PCP antibody concentrations (12/13 serotypes) increased significantly at month 1 and 12 post-vaccination. CONCLUSIONS: Kidney transplant recipients show a significant humoral response after vaccination with PCV13. Functional antibody response exists, but is not as vigorous as in healthy adults.

Sex-Specific Differences in HLA Antibodies after Pneumococcal Vaccination in Kidney Transplant Recipients.

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.