IVIg and LPS Co-stimulation Induces IL-10 Production by Human Monocytes, Which Is Compromised by an FcγRIIA Disease-Associated Gene Variant

Intravenous Immunoglobulin (IVIg) is used to treat autoimmune or inflammatory diseases, but its mechanism of action is not completely understood. We asked whether IVIg can induce interleukin-10 (IL-10) and reduce pro-inflammatory cytokine production in human monocytes, and whether this response is reduced in monocytes from people with an Fcγ receptor IIA (FcγRIIA) gene variant, which is associated with increased risk of inflammatory diseases and poor response to antibody-based biological therapy. IVIg increased IL-10 production and reduced pro-inflammatory cytokine production in response to bacterial lipopolysaccharide (LPS), which required FcγRI and FcγRIIB and activation of MAPKs, extracellular signal-regulated kinase 1/2 (ERK1/2), and p38. IL-10 production was lower and pro-inflammatory cytokine production was higher in monocytes from people with the FcγRIIA risk variant and the risk variant prevented IL-10 production in response to (IVIg+LPS). Finally, we show that IVIg did not induce MAPK activation in monocytes from people with the risk variant. Our results demonstrate that IVIg can skew human monocytes to an anti-inflammatory, IL-10-producing activation state, which is compromised in monocytes from people with the FcγRIIA risk variant. This research has profound implications for the use of IVIg because 25% of the population is homozygous for the FcγRIIA risk variant and its efficacy may be reduced in those individuals. In addition, this research may be useful to develop new therapeutic strategies to replace IVIg by cross-linking FcγRIs and FcγRIIBs to promote anti-inflammatory macrophage activation, independent of the FcγRIIA genotype

A patient‐led, peer‐to‐peer qualitative study on the psychosocial relationship between young adults with inflammatory bowel disease and food

Abstract Background Inflammatory bowel diseases (IBDs) are chronic gastrointestinal diseases that negatively affect the enjoyment of food and engagement in social and cultural gatherings. Such experiences may promote psychosocial challenges, an aspect of IBD often overlooked and under‐supported in clinical settings and research. Objectives This study explored the psychosocial experiences that young adults with IBD have with food via a qualitative patient‐led research process. Methods Trained patient researchers conducted this study by engaging peers via semi‐structured interviews and focus groups in a three‐step co‐design process. Participants (n = 9) identified the research topic (SET), explored the topic and identified emerging themes (COLLECT), refined themes and made recommendations for healthcare system change (REFLECT). Results Themes that emerged included: ‘Experimenting with Food’, ‘Evolution Over Time’, ‘Diet Changes are Emotional’ and ‘Role of Stigma’. Participants identified the significance and frustrations of repeated testing and experimenting with food compatibility, and noted nuances in food relationships as they gain knowledge and experience over time. They emphasized the importance of maintaining a sense of hope throughout and wished to impart this to newly diagnosed patients. Conclusion Participants experience numerous psychosocial challenges as they strive to manage their diet, noting gaps in support available from IBD practitioners. Participants made practical recommendations for healthcare system change to improve patient outcomes, highlighting the importance of sharing stories and collaboratively including patients in the development of new services and protocols. Authors recommend further research in this area to build a body of knowledge and support that helps IBD patients maintain hope while navigating challenges with food. Patient or Public Contribution The first four authors on this paper were the lead researchers in this study's design and analysis and identify as patients; they conducted the research with this identity at the forefront following a peer‐to‐peer research model. These authors were mentored by patient researchers who also contributed to the manuscript, and the research process itself was co‐lead and directed by other patient participants and consultants. Results and recommendations coming from this paper came directly from patient participants