Functional activity of CD40 antibodies correlates to the position of binding relative to CD154.

In this study we describe the characterization of a panel of 12 anti-mouse CD40 monoclonal antibodies (mAb). Characterization was performed in terms of antibody-binding site relative to the CD154 ligand, and the relationship between position and functional outcome of binding. The antibodies divided into three groups. The first were strong inhibitors of CD154 binding, and induced strong proliferative and activation signals to B cells. Two antibodies gave intermediary inhibition and comparable levels of activation. The remaining antibodies were found to bind outside the CD154 binding site and were poor inducers of B-cell activation. Data presented show a strong correlation between location of mAb binding and the resultant activation signal delivered. This correlation is shown to be independent of the isotype of the antibody involved and of its affinity. Implications of these findings are discussed.

Enhanced in vivo immune responses to bacterial lipopolysaccharide by exogenous CD40 stimulation.

The lack of specific T-cell help in immune responses to thymus-independent antigens results in weak, predominantly immunoglobulin M-mediated immunity with little or no memory. In the work presented here we show how the exogenous stimulation of CD40 by monoclonal antibodies can mimic T-cell help, resulting in enhanced immune responses which are protective against bacterial infection.

Extended follow-up in 212 long-term allogeneic bone marrow transplant survivors. Issues of quality of life.

A group of 235 allogeneic marrow recipients were contacted at least one year following their BMT to obtain information on their quality of life; 212 (90%) agreed to participate in this survey. A total of 162 adults and 50 pediatric survivors were interviewed during clinic visits (5%) or over the telephone (95%). Changes in productive activity and marital status at the time of interview were studied, as well as the presence of physical symptoms and perception of a general sense of well-being. Older transplant recipients were observed to have a significantly higher incidence of chronic graft-versus-host disease, common colds, and skin changes when compared with pediatric transplant recipients (P < 0.01). Older subjects were also more likely to require any type of regular medication. Younger survivors were rated with a higher Karnofsky performance status and global subjective score. There were no significant differences between patients who received TBI as part of the conditioning regimen and those who did not, with the exception of increased cataract development in pediatric patients receiving TBI (P < 0.008). We conclude that most allogeneic marrow transplant survivors, especially those individuals of younger age at the time of their transplants, are doing well in the domains tested.

Dynamic assessment of quality of life after autologous bone marrow transplantation.

To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.