Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.

While the guidelines for vaccination in renal transplant recipients recommend the use of pneumococcal polysaccharide (PPS) and tetanus toxoid (TT), their efficacy in immunocompromised renal transplant recipients is not known. Here we tested the effect of everolimus on immune responses after vaccination by measuring the capacity of 36 stable renal transplant recipients to mount cellular and humoral responses after vaccination. Twelve patients in each treatment arm received immunosuppressive therapy consisting of prednisolone (P) plus cyclosporine (CsA), mycophenolate sodium (MPA), or everolimus. Patients were vaccinated with the T-cell-dependent antigens immunocyanin and TT, and the T-cell-independent PPS. Treatment with CsA partially inhibited and MPA completely abolished the capacity to mount a primary humoral response, whereas everolimus left this largely intact. Recall responses were inhibited by MPA only. All drug combinations inhibited cellular responses against TT. In patients treated with MPA, B-cell numbers were severely reduced. Thus, combined with P, treatment with MPA completely disturbed primary and secondary humoral responses. Everolimus or CsA allowed the boosting of T-cell-dependent and -independent secondary humoral responses. Treatment with everolimus allowed a primary response.

A significant correlation was observed between interstitial infiltrates of CD20+ cells and CD3+ cells (r=0.720, P<0.001) suggesting that if B-cell infiltrates are present during rejection, they occur with T-cell infiltrates in a concurrent fashion. In contrast to previous reports, no relation was found between the number of CD20+ cells, in aggregates or in a scattered interstitial pattern, and response to conventional therapy. Remarkably, CD3+T cell aggregates did predict a favorable renal outcome.