A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resistant to collagen-induced arthritis.

Collagen-induced arthritis (CIA) represents an animal model of autoimmune polyarthritis with significant similarities to human rheumatoid arthritis that can be induced upon immunization with native type II collagen. As in rheumatoid arthritis, both cellular and humoral immune mechanisms contribute to disease pathogenesis. Genotypic studies have identified at least six genetic loci contributing to arthritis susceptibility, including the class II MHC. We have examined the mechanism of Ab-mediated inflammation in CIA joints, specifically the role of complement activation, by deriving a line of mice from the highly CIA-susceptible DBA/1LacJ strain that are congenic for deficiency of the C5 complement component. We show that such C5-deficient DBA/1LacJ animals mount normal cellular and humoral immune responses to native type II collagen, with the activation of collagen-specific TNF-alpha-producing T cells in the periphery and substantial intra-articular deposition of complement-fixing IgG Abs. Nevertheless, these C5-deficient mice are highly resistant to the induction of CIA. These data provide evidence for an important role of complement in Ab-triggered inflammation and in the pathogenesis of autoimmune arthritis.

Neonatal morbidity at 34-37 weeks: the role of ruptured membranes.

OBJECTIVE: Evaluate neonatal morbidity in deliveries occurring between 34 0/7 and 36 6/7 weeks' gestation, comparing outcomes in pregnancies complicated by preterm premature rupture of membranes with those in which delivery occurred with intact membranes prior to the onset of labor. METHODS: The obstetric database was reviewed for a 5-year period. Healthy gravidas delivering nonanomalous singleton gestations from vertex presentations were evaluated, with corticosteroid or antibiotic administration or both noted. The neonatal database was reviewed for the following complications: admission to the neonatal intensive care unit, need for assisted ventilation, and development of hyaline membrane disease, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, or culture-proven sepsis. Groups were compared using chi2 tests. The power of this study to detect a ten-fold decrease in the likelihood of neonatal complications at the P<.05 significance level was greater than 90%. RESULTS: Of 853 eligible pregnancies, 414 (48.5%) gravidas had ruptured membranes prior to the onset of active labor. No difference existed between groups in the number of patients who had received corticosteroids during pregnancy, but patients with ruptured membranes were more likely to have received antibiotics prior to delivery. No neonatal deaths occurred, and neonatal morbidity was low in both groups. CONCLUSION: No clinically significant difference exists in neonatal outcome between 34 0/7 and 36 6/7 weeks' gestation as the result of membrane status prior to the onset of labor.