Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

BACKGROUND: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. METHODOLOGY: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. RESULTS/CONCLUSION: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM

Severe Obstetric Brachial Plexus Palsies Can Be Identified at One Month of Age

OBJECTIVE: To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age. METHODS: Severe OBPP was defined as neurotmesis or avulsion of spinal nerves C5 and C6 irrespective of additional C7-T1 lesions, assessed during surgery and confirmed by histopathological examination. We first prospectively studied a derivation group of 48 infants with OBPP with a minimal follow-up of two years. Ten dichotomous items concerning active clinical joint movement and needle electromyography of the deltoid, biceps and triceps muscles were gathered at one week, one month and three months of age. Predictors for a severe lesion were identified using a two-step forward logistic regression analysis. The results were validated in two independent cohorts of OBPP infants of 60 and 13 infants. RESULTS: Prediction of severe OBPP at one month of age was better than at one week and at three months. The presence of elbow extension, elbow flexion and of motor unit potentials in the biceps muscle correctly predicted whether lesions were mild or severe in 93.6% of infants in the derivation group (sensitivity 1.0, specificity 0.88), in 88.3% in the first validation group (sensitivity 0.97, specificity 0.76) and in 84.6% in the second group (sensitivity of 1.0, specificity 0.66). INTERPRETATION: Infants with OBPP with severe lesions can be identified at one month of age by testing elbow extension, elbow flexion and recording motor unit potentials (MUPs) in the biceps muscle. The decision rule implies that children without active elbow extension at one month should be referred to a specialized center, while children with active elbow extension as well as active flexion should not. When there is active elbow extension, but no active elbow flexion an EMG is needed; absence of MUPs in the biceps muscle is an indication for referral