Association of T Gamma Delta-CD16+ Cells and Anti-CMV Immunoglobulins in the Prevention of CMV Infection
Status:
Not yet recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
CMV infection in transplantation remains the most frequent infectious complication causing
increased morbidity and mortality. International recommendations advocate prevention of this
infection by instituting direct antiviral treatment or monitoring viral replication by PCR
with the start of curative antiviral treatment when the DNAemia is positive.
The risk of CMV infection varies according to the serostatus of the donor (D) and recipient
(R) at the time of transplantation. In the absence of prophylaxis, CMV infection occurs in
60-80% of D+R-, 50-60% of D+R+ and 25-50% of D-R+.
The humoral anti-CMV response is represented by the production of antibodies to envelope
proteins (gB and gH) and to molecules involved in viral attachment and entry into target
cells. However, the majority of CMV-specific antibodies do not have antiviral neutralising
activity. The investigators have identified a new player in the specific anti-CMV response
expressing the Fc RIIIa receptor (CD16), that interacts with anti-CMV immunoglobulins (Ig):
the Tgamma-delta V delta 2-negative lymphocyte (LTgdVd2neg). This lymphocyte subpopulation
shows persistent expansion in the peripheral blood of kidney transplant patients with CMV
infection. These cells express an effector-memory phenotype (CD45RA+/CD27-). This expansion
is associated with resolution of infection in patients. The investigators have shown that
CD16 is specifically and constitutively expressed on the surface of CMV-induced LTgdVd2neg in
healthy volunteers and kidney transplant patients. The investigators have observed that one
of the antiviral activities of anti-CMV IgG lies in its binding to the Fc RIIIa receptor
(CD16) on the surface of LTgdVd2neg. The anti-CMV IgGs capturing virions thus activate CD16+
LTgdVd2neg with production of IFN interferon which in turn is responsible for inhibition of
CMV viral multiplication.
Anti-CMV IgG is a recommended therapeutic option, with a marketing authorisation for the
prevention of CMV infection in kidney transplantation in Europe and a Temporary Authorisation
for Use in France.
Thus, R+ patients expressing a significant level of LTgdVd2neg CD16+ at D0 of transplantation
could be protected against CMV, in the absence of direct antiviral treatment by the addition
of anti-CMV Ig.