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Autoantibody formation against Factor H (FH) is found in 7–10% of patients who are diagnosed with atypical haemolytic uraemic syndrome (aHUS). These autoantibodies predominately target the C-terminal cell binding recognition domain of FH and are associated with absence of FHR1. Additional autoantibodies have also been identified in association with aHUS, for example autoantibodies to Factor I. Based on this, and that there are genetic mutations in other complement regulators and activators associated with aHUS, we hypothesised that other complement regulator proteins, particularly surface bound regulators in the kidney, might be the target for autoantibody formation in aHUS. Therefore, we assayed serum derived from 89 patients in the Newcastle aHUS cohort for the presence of autoantibodies to CD46 (membrane cofactor protein, MCP), CD55 (decay accelerating factor, DAF), CD35 (complement receptor type 1, CR1; TP10) and CD59. We also assayed 100 healthy blood donors to establish the normal levels of reactivity towards these proteins in the general population. Recombinant proteins CD46 and CD55 (purified from Escherichia coli) as well as soluble CR1 (CD35) and oligomeric C4BP-CD59 (purified from eukaryotic cell media) were used in ELISA to detect high responders. False positive results were established though Western blot and flow cytometric analysis. After excluding false positive responders to bacterial proteins in the CD46 and CD55 preparations, and responses to blood group antigens in CD35, we found no significant level of patient serum IgG reactivity with CD46, CD55, CD35 or CD59 above that detected in the normal population. These results suggest that membrane anchored complement regulators are not a target for autoantibody generation in aHUS.

OmCI is an ectoparasite derived bifunctional lipocalin that inhibits complement (C) by binding to C5 and also captures the proinflammatory eicosanoid leukotriene B4 (LTB4). We present the crystal structure of recombinant bacterial bOmCI with and without LTB4 at 2.1 A resolution, and test the relative contributions of C5 inhibition and LTB4 binding to amelioration of experimental immune complex acute lung injury alveolitis (IC-ALI). The structure shows why OmCI is able to accommodate LTB4, arachidonic acid (AA) and 12-OH hydroxyeicosatetraenoic acid (HETEs), but not cysteinyl leukotrienes, prostaglandins or thromboxanes. It also reveals that only minor structural changes occur when bOmCI is bound to LTB4 rather than palmitoleic acid (C16H30O2) which is the dominant fatty acid in the binding pocket of recombinant bOmCI. In accord with the minor structural changes and use of opposite faces of OmCI for C5 binding and entry of LTB4, the two activities of the protein appear to be entirely independent - since the binding kinetics to LTB4 do not change when bOmCI is bound to C5 and the affinity for C5 and inhibition of C activation is unaltered by binding LTB4. In a mouse model of IC-ALI OmCI inhibited neutrophil recruitment and microvascular damage, and reduced protein exudation in the bronchoalveolar space. To examine the relative importance of OmCIs independent inhibitory activities in IC-ALI, OmCI was saturated with LTB4. The saturated protein was a less potent inhibitor of lung inflammation, though both LTB4 binding and C inhibition were required for maximum effect. The dual activity of OmCI may have advantages over conventional biotherapeutics, such as monoclonal antibodies, which typically target only single components of the immune system

A case of enteric fever was defined as isolation of Salmonella enterica serotypes typhi or paratyphi A, B and C from blood, or from stool or urine in a patient with clinical features compatible with enteric fever. Cases were considered to be imported if they occurred following travel within the prior 8 weeks. Patients were identified from a database listing all diagnoses on patients seen at the emergency walk-in clinic at the HTD or admitted to the Infectious Diseases ward at University College London Hospital between 2000 and 2009. Epidemiological, demographic, clinical, radiological, microbiologic and treatment data were gathered retrospectively.