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

Serum neopterin/creatinine values correlate with severity of symptoms caused by cytomegalovirus infection in renal transplant recipients

Serum neopterin/creatinine ratios were longitudinally measured in 86 renal transplant recipients from the day before transplantation until 4 months after transplantation, and the relationship to the clinical symptoms of cytomegalovirus (CMV) infection was studied. Infection with cytomegalovirus occurred in 23 patients, 11 cases of which were due to primary infection. Symptoms caused by CMV infection were more severe in male patients, in patients who had received prior antirejection treatment, and in patients with primary CMV infection. The measurement of serum neopterin/creatinine ratios proved to be a marker for the severity of symptoms caused by CMV infection, as peak values were significantly higher in eight patients with CMV disease than in patients with no or only mild symptoms of CMV infection (P<0.05). Moreover, in seven out of eight cases of CMV disease, serum neopterin/creatinine ratios started to rise up to 2 weeks before CMV infection was proven by serology