Early recovery of CD4+ T lymphocytes in children on highly active antiretroviral therapy. Dutch study group for children with HIV infections.

INTRODUCTION: Regeneration of CD4+ T lymphocytes has been shown to be thymus-dependent in bone marrow transplant recipients and after intensive chemotherapy. The rate of CD4+ T cell regeneration is correlated positively with enlargement of the thymus, as shown on radiographs, and higher rates of CD4+ T lymphocyte regeneration were observed in children as compared with adults, consistent with thymic function diminishing with age. We hypothesized that in HIV infected patients CD4+ T cell recovery during highly active antiretroviral therapy (HAART) may also be thymus dependent. Therefore, repopulation of naive (CD45RA+), memory (CD45RO+) and total CD4+ T lymphocytes and total CD8+ T lymphocytes in peripheral blood was assessed in 13 HIV infected children during the initial 3 months of HAART. RESULTS: Significantly higher recovery rates of naive, memory and total CD4+ T cells were observed in children below the age of 3 years as compared with older children. Kinetics of total CD8+ T cells showed no relation to age. Moreover, recovery rates of naive CD4+ T cells in patients below 3 years of age were 10-40 fold higher as compared with previously reported naive CD4+ T cell recovery rates in adults on HAART. CONCLUSIONS: High recovery rates of naive, memory and total CD4+ T cells can be achieved in children below 3 years of age. Changes in CD8 counts did not correlate with age. These results indicate that regeneration of CD4+ T cells during HAART may be a thymus-dependent process.

Hepatic GVHD after HLA-haploidentical bone marrow transplantation in children with severe combined immunodeficiency: the effect of ursodeoxycholic acid.

We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T-cell-depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft-versus-host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct syndrome was confirmed by liver biopsies. Because corticosteroids and cyclosporin A induced only a partial response, ursodeoxycholic acid (UDCA) was added to their treatment schedule. Serum bilirubin and liver enzymes returned to normal within months. A control liver biopsy showed normal and proliferating bile ducts without cholestatic damage. We conclude that UDCA was well tolerated and may be of value as an additional treatment for hepatic GVHD in SCID.

Defective antipneumococcal polysaccharide antibody response in children with recurrent respiratory tract infections.

BACKGROUND: Recurrent pyogenic infections are known to occur in patients with an impaired response to polysaccharide antigens. We investigated the occurrence of deficient responses to pneumococcal capsular polysaccharides in patients with recurrent respiratory tract and recurrent systemic infections. METHODS: Forty-five patients, 1.7 to 17.1 years of age, were immunized with 23-valent pneumococcal polysaccharide vaccine. Antibody levels to seven pneumococcal serotypes (3, 4, 6A, 9N, 14, 19F, 23F) were determined by ELISA before and after immunization. In addition, patients received a booster immunization with diphtheria toxoid, tetanus toxoid, and poliomyelitis virus vaccine. RESULTS: Thirty-five patients had normal serum immunoglobulin levels. Five of these patients (14%) had low antipneumococcal preimmunization antibody levels and failed to respond to pneumococcal vaccination, whereas the response to booster immunization with protein antigens was appropriate. Three patients were younger than 3 years old, and one had a family history of IgG2 deficiency. Low IgG developed in a fifth patient during follow-up. Ten patients had a humoral immunodeficiency. Seven of these patients failed to respond to pneumococcal vaccination. CONCLUSIONS: We conclude that a defective immune response to polysaccharide antigens in patients requires long-term follow-up to distinguish transient maturational delay from a persistent selective impaired response to polysaccharide antigens, which on occasion may precede the development of humoral immunodeficiency disease.