An increased number of thalassaemia patients treated with effective chelation therapy protocols are achieving body iron levels similar to those of normal individuals. Iron chelation therapy has also been recently used in a number of other categories of patients with no excess body iron load such as neurodegenerative, renal and infectious diseases. Chelation therapy in the absence of iron overload in the latter conditions raises many safety issues including chelator overdose toxicity and toxicity related to iron and other essential metal deficiencies. Preliminary preclinical and clinical toxicity evidence suggest that deferoxamine and deferasirox can only be safely used for these non-iron loaded conditions for short-term treatments of a few weeks, whereas deferiprone can be used for longer term treatments of many months. The selection of the chelating drug and appropriate dose protocols for targeting specific organs and conditions is critical for the safety of patients with normal iron stores. Chelation therapy is likely to play a major role as adjuvant, alternative or main therapy in many non-iron loading conditions in the forthcoming years.
Objective
Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in fact a subpopulation of B cells and exists in higher primates remains unclear. The objective of this study was to identify NKB cells in primates and study the impact of HIV/SIV infections.
Design and Methods
NKB cells were quantified in both naïve and lentivirus infected rhesus macaques and humans by excluding lineage markers (CD3, CD127), and positive Boolean gating for CD20, NKG2A/C and/or NKp46. Additional phenotypic measures were conducted by RNA-probe and traditional flow cytometry.
Results
Circulating cytotoxic NKB cells were found at similar frequencies in humans and rhesus macaques (range, 0.01 to 0.2% of total lymphocytes). NKB cells were notably enriched in spleen (median, 0.4% of lymphocytes), but were otherwise systemically distributed in tonsil, lymph nodes, colon, and jejunum. Expression of immunoglobulins was highly variable, but heavily favoured IgM and IgA rather than IgG. Interestingly, NKB cell frequencies expanded in PBMC and colon during SIV infection, as did IgG expression, but were generally unaltered in HIV-infected human subjects.
Conclusion
These results suggest a cell type expressing both NK and B cell features exists in rhesus macaques and humans and are perturbed by HIV/SIV infection. The full functional niche remains unknown, but the unique phenotype and systemic distribution could make NKB cells unique targets for immunotherapeutics or vaccine strategies.
The data suggest that it may not be necessary to continue performing gastroscopy in all patients preparing for gastric banding. The data collected support the policy of a selective use of gastroscopy, only focusing on patients suffering from gastroesophageal symptoms. By following this strategy, the rate of preoperative gastroscopies can be reduced safely by 80%.
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