Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells.

High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2–59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNFα, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery.

Background and AimsPrimary sclerosing cholangitis [PSC] is an idiopathic chronic disorder of the hepatobiliary system associated with inflammatory bowel disease [IBD], mainly ulcerative colitis [UC]. Colitis in patients with PSC and UC [PSC-UC] exhibits characteristic features and is linked to increased colon cancer risk. Genetic studies have identified immune-related susceptibility genes that only partially overlap with those involved in IBD. These observations suggest that PSC-UC may represent a distinct form of IBD. It remains to be elucidated whether different immune mechanisms are involved in colitis in these patients. We aimed to evaluate systemic and intestinal T cell and innate lymphoid cell [ILC] responses, previously associated with IBD, in patients with PSC-UC compared with patients with UC and healthy controls.MethodsBlood samples and colorectal biopsies were collected from patients with PSC-UC, patients with UC, and healthy controls. T cell and ILC phenotypes were analysed by multicolour flow cytometry.ResultsChemokine receptor [CCR] profiling of circulating T cells showed decreased CCR6-CXCR3+ Th1 cells in PSC-UC, but increased CCR6-CCR4+ Th2 cells only in UC, whereas increased CCR6+CCR4+ Th17 cells were found in both patient groups compared with healthy controls. Increased frequencies of IFN-γ secreting T cells were found in the colon of patients with PSC-UC compared with UC. Interestingly, we observed accumulation of ILC in the colon in PSC-UC.ConclusionsOur study suggests that PSC-UC represents a different immunological disorder from UC, characterised by increased intestinal Th1 and ILC responses. These results provide further evidence that PSC-UC may represent a distinct form of IBD.

paralysis is likely a central driver of immune dysfunction resulting in increased vulnerability to both acute and chronic infections during childhood. 3