Early increase of peripheral B cell levels in kidney transplant recipients with CMV infection or reactivation.
BACKGROUND
Cytomegalovirus (CMV) infection or reactivation is a frequent complication of renal transplantation. Diagnosis of these conditions relies on the detection of circulating antigen, or of specific IgM and/or IgG, which develop over several weeks. Evocative clinical features may be detected earlier, but lack specificity. Rapid and early changes in the partition of lymphocyte subsets could be an additional indication of pending CMV infection.


METHODS
A systematic follow-up of peripheral B lymphocytes identified immunophenotypically by the determination of surface immunoglobulins (sIg), performed in 97 kidney transplant recipients, allowed to identify transient increases apparently predictive of CMV primo-infection or reactivation over the next 3 months. To better define the nature of these B cells, an extended investigation was performed for 14 prospective patients. In addition to surface Ig, membrane CD19, HLA-DR, and CD80 expression were explored. The cytoplasmic presence of mu, kappa, and lambda chains was also examined. B cell function was investigated using the ELISPOT technique, which allows an enumeration of the populations of IgG, IgA, and IgM secreting B cells.


RESULTS
Retrospective analysis of the clinical outcome of the cohort of 97 patients evidenced that early transient increases in B cell levels were significantly (P<0.0001) associated with CMV infection. The same trend was noted in the smaller series of patients who benefited from a more extensive investigation of B cells, 10 of whom presented clinical or biological signs of CMV infection. Mature B cells, expressing surface Ig, CD19, DR, and CD80 are those presenting transient increases. No significant variation of preB (cmu+/kappalambda-) or activated (spot-forming) cells was evidenced in these patients.


CONCLUSIONS
Individual examination of each patient's immune reconstitution profile allows to detect transient peaks of mature B cell during the initial immunosuppressive therapy, that appear to be predictive of oncoming CMV infection or reactivation.
Besançon-Watelet
C
C
Immunology Laboratory, Nephrology Department, Faculté de Médecine and CHU, Vandoeuvre les Nancy, France.
De March
A K
AK
Renoult
E
E
Kessler
M
M
Béné
M C
MC
Faure
G C
GC
Sarda
M N
MN
D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000009:adverse effects*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D018941:Antigens, CD19; D018122:B7-1 Antigen; D006684:HLA-DR Antigens