Belatacept may result in profound and persistent loss of cytomegalovirus‐specific cell‐mediated immunity: A case report

Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor–Intolerant Patients

“…In fact, control patients demonstrated a decrease in naive double-cytokine CMV-specific T cells, suggesting possible impaired antiviral immune response, whereas belatacept-switched patients demonstrated no significant decrease in CMV- or EBV-specific T-cell response ( Supplementary Tables S3 and S4 ), with memory cells likely providing protection against clinically CMV infection. 36 These findings are in contrast to other reports of impaired CMV immune response, 17 potentially because we used peptides representing multiple CMV antigens for stimulation and measured the expression of multiple cytokines simultaneously, allowing for a more complete evaluation of antiviral response. The observation of preserved antiviral function in the face of impaired alloimmunity could reflect the fact that TCR avidity toward viral antigens is generally higher than alloantigens, requiring less costimulation and therefore more difficult to inhibit with costimulation-inhibitor.…”

“…In addition, increased rates of CMV DNAemia and disease and impaired development of the anti-CMV cellular immune response have been reported. 15 , 16 , 17 , 18 There is a lack of previous ex vivo data in human subjects receiving belatacept comparing in parallel the impact of belatacept treatment on immune phenotype, alloimmune, and antiviral immune response using a flow cytometry–based approach, with previous data limited to exogenous addition of belatacept in vitro . 19 , 20 Therefore, it is important to understand how CMV-specific T-cell immunity may be affected in the context of kidney transplant after belatacept switch from CNI therapy.…”

Belatacept as a Treatment Option in Patients with Severe BK Polyomavirus Infection and High Immunological Risk—Walking a Tightrope between Viral Control and Prevention of Rejection

“…Chavarot et al describe a sevenfold increase in the incidence of CMV disease and an atypical, aggressive disease phenotype in their patients [ 19 ]. In response to that study, Kleiboeker et al presented the case of a 56-year-old male patient who lost his CMV-specific cell-mediated immunity after conversion to belatacept, and they hypothesized that this was a possible reason for the observations by Chavarot et al [ 20 ]. To note, in contrast to our patients, who received belatacept at a dose of 5 mg/kg of body weight, in the case presented by Kleiboeker et al belatacept was dosed at 10 mg/kg of body weight [ 20 ].…”

“…In response to that study, Kleiboeker et al presented the case of a 56-year-old male patient who lost his CMV-specific cell-mediated immunity after conversion to belatacept, and they hypothesized that this was a possible reason for the observations by Chavarot et al [ 20 ]. To note, in contrast to our patients, who received belatacept at a dose of 5 mg/kg of body weight, in the case presented by Kleiboeker et al belatacept was dosed at 10 mg/kg of body weight [ 20 ]. However, in the study by Chavarot et al belatacept was administrated at 5 mg/kg of body weight [ 19 ].…”

Cytomegalovirus antiviral stewardship in solid organ transplant recipients: A new gold standard

“…Two cases were in patients receiving belatacept for maintenance immunosuppression, one of which was described in a previous publication. 32 The third was in the setting of secondary prophylaxis, potentially due to interrupted therapy, although this could not be confirmed. Both patients on primary prophylaxis successfully resumed letermovir after clearance of viral loads <1000 IU/ml with positive outcomes.…”