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Accepted: September 5, 2000
Pneumococcal polysaccharide (PPS) antibody deficiency occurs in some children immunosuppressed following cardiac transplantation in early childhood. We studied lymphocyte subset populations in these children to identify patterns associated with antibody deficiency, particularly in CD21 1 B cells.
Lymphocyte surface markers CD3, CD4, CD8, CD19, and CD21 were measured on whole blood by FACS analysis in four patient groups: cardiac transplant patients who did and did not respond to PPS, nontransplanted cardiac patients, and normal controls. Absolute cell numbers were compared with agerelated normal ranges. The proportion of children with values below the age-related 25th percentile in each group was compared.
Normal controls had significantly more CD31, CD81, and CD191 cells, even when age-related differences were accounted for. Control groups had significantly more CD19 cells than transplant patients and transplanted PPS responders and cardiac controls had more mature B cells (CD211) than transplanted PPS nonresponders.
PPS antibody deficiency following pediatric cardiac transplantation may be related to an immaturity in B cells due to immunosuppression commenced in early childhood.
KEY WORDS: Polysaccharide antibodies; antibody deficiency; immunosuppression; cardiac transplantation; B-cell maturation; CD21 receptor.
INTRODUCTION
Children who undergo cardiac transplantation in early childhood more often have a persisting deficient antipneumococcal polysaccharide antibody response compared with those transplanted when older (1). All the patients receive ongoing immunosuppression with cyclosporin A (CSA) and azathioprine. These findings therefore suggest that potent antilymphocyte immunosuppression may interfere with the maturing immune system if given before antipolysaccharide B lymphocyte responses have developed. While the mechanism for this effect is unclear, it is of note that Tindependent type 2 antigen-responsive B cells that use calcium-dependent intracellular signaling pathways are inhibited by CSA (2, 3). Moreover, azathioprine acts preferentially on human B cells (4) and impairs terminal differentiation of T1-2 antigen-stimulated B cells (5).
Polysaccharide antibody responses are absent or impaired in infants and young children but mature through childhood (6 - 8). Encapsulated pneumococcal subtypes activate complement via the alternative pathway (9) by binding to C3d. The complex associates with CD21 on the B cell surface, inducing signal transduction (reviewed in 10). Neonatal cord blood and infant splenic marginal zone B cells show decreased CD21 expression compared with adult peripheral B cells (11) and are unresponsive to pneumococcal polysaccharide antigen in...