Complement activation during OKT3 treatment: A possible explanation for respiratory side effects

Complement activation during OKT3 treatment: A possible explanation for respiratory side effects. Respiratory side effects that sometimes occur during treatment with anti-CD3 MAb OKT3 might result from pulmonary sequestration of activated neutrophils. Therefore, we studied complement activation in relation to activation and pulmonary sequestration of neutrophils during antirejection treatment with OKT3. In each of nine patients studied, plasma C3a-desarg and C4b/c levels increased compared with pretreatment values already in the first sample taken 15 minutes after the first dose of OKT3 (P < 0.05), with peak values at 15 and 30 minutes, respectively. Levels of neutrophil degranulation product elastase (complexed to α1-antitrypsin) also increased already at 15 minutes after the first dose of OKT3 (P < 0.05), which is before elevated levels of the cytokines TNFα, IL-6 or IL-8 were detectable. In contrast, upon subsequent OKT3 administrations or in the control group treated with methylprednisolone, neither complement activation, cytokine release nor neutrophil degranulation occurred. In five studied patients treated with OKT3, pulmonary sequestration of radiolabeled granulocytes was observed from 3 until 15 minutes after the first dose of OKT3, together with peripheral blood granulocytopenia, which lasted at least 30 minutes. In conclusion, we demonstrate a simultaneous activation of complement and pulmonary sequestration of activated granulocytes immediately following the first dose of OKT3. These phenomena may be involved in the development of respiratory side effects complicating this therapy

Implantation of Cultured Thymic Fragments in Patients With Acquired Immunodeficiency Syndrome

• Cultured thymic fragments were implanted in one patient with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and in eight AIDS patients with opportunistic infections (Ols, four patients), Kaposi’s sarcoma (KS, two patients), or both (two patients). Thereafter, objective clinical improvement was noted in one patient with 01, and a stable symptom-free condition was observed in the ARC patient and in two other patients with Ols. However, the ARC patient and two of the three patients with Ols developed infections three to six months after implantation. A fourth case of 01 and the patients with KS showed progression of the disease. Peripheral blood investigations for counts of total leukocytes, lymphocytes, and T-lymphocyte subsets as well as for lymphocyte stimulation with mitogens showed no changes interpretable as an improvement of the cellular immune deficiency status. We conclude that cultured thymic fragments have no distinct in vivo effect on the course of AIDS, except for a temporary clinical improvement or a period of stable condition in some patients with Ols

Persistence of Human Immunodeficiency Virus Antigenemia in Patients With the Acquired Immunodeficiency Syndrome Treated With a Reverse Transcriptase Inhibitor, Suramin: Ten-Patient Case-Control Study

Ten homosexual men with the acquired immunodeficiency syndrome were included in a serologic follow-up study (duration, 40 weeks) of human immunodeficiency virus (HIV) antigenemia. Five of these men were treated with the reverse transcriptase inhibitor, suramin, for a period of 19 to 37 weeks. In contrast with reported changes in HIV antigen levels after treatment with zidovudine, HIV antigenemia persisted in the suramin-treated group, as well as in the untreated group. No clinical or immunologic improvement was seen in either group within the observation period. These data add evidence to the notion that monitoring HIV antigen levels helps to assess the efficacy of antiviral therapy

Immune responsiveness in renal transplant recipients: mycophenolic acid severely depresses humoral immunity in vivo

BACKGROUND: Current immunosuppressive drug treatments for renal transplant recipients result in high one-year graft survival rates. Despite adequate suppression of the immune response directed to the allograft, the immune system remains able to cope with many infectious agents. METHODS: To define the influence of distinct immunosuppressive treatment protocols, primary and secondary cellular and humoral immune responses in groups of renal transplant recipients were studied: patient treated with prednisolone and cyclosporine A (P/CsA); with IgA CD3 monoclonal antibody as a rejection treatment superimposed on prednisolone and cyclosporine A (IgA CD3 mAb+P/CsA); and with prednisolone, cyclosporine A and mycophenolate mofetil (P/CsA/MMF). RESULTS: Primary in vitro proliferative responses to the protein antigen keyhole limpet hemocyanin (KLH) were not significantly disturbed in P/CsA treated patients, or in IgA CD3 mAb+P/CsA and P/CsA/MMF treated patients. In vitro proliferative responses to the recall antigen tetanus toxoid (TT) were similarly unaffected. Antigen-specific antibody responses to immunization with KLH and TT were not affected by treatment with P/CsA, or by IgA CD3 mAb+P/CsA, but were severely disturbed in patients treated with P/CsA/MMF. All patients displayed a profound inhibition of the delayed-type hypersensitivity skin reactivity to KLH and recall antigens. Nevertheless, in most patients with P/CsA treatment, T cell infiltrates were observed in skin biopsies from the site of KLH challenge, while expression of intercellular cell adhesion molecule-1 (ICAM-1) expression in challenged skin was significantly decreased in these patients. The balance between T helper 1 and T helper 2 cells was unaffected by immunosuppressive treatments during one year of follow-up. CONCLUSIONS: Immunosuppressive drug treatment with P/CsA inhibits delayed-type hypersensitivity skin reactions to both primary and frequently encountered antigens. Histological studies indicate an effect on ICAM-1 expression, leaving the influx of CD3pos T cells unaffected. Administration of a 10-day course of IgA CD3 mAb does not add profound immunosuppressive effects on the measured parameters. In contrast, addition of treatment with MMF profoundly decreases both primary and secondary humoral immune responsiveness in vivo. Finally, no effect of the studied immunosuppressive drugs on Th1/Th2 balance in vivo was measure