Immunofrailty defines the ability of an individual to cope with chronic and acute inflammatory diseases. It is a complex condition with a wide range of causes, that all lead to high levels of chronic inflammation. Extensive scientific research demonstrated that chronic inflammation is the primary driver of the majority chronic diseases and ageing
Our Immunofraility Model (IFM) uses a systems science approach to model the complex and diverse mechanisms of degradation in immune system structure and function in different inflammatory diseases (IDs). It attempts to map causal relationships between the progression of chronic-IDs and the disruption of the immune system’s structure and functions that are seen in serious acute-IDs.
IFM considers alterations to:
- The integrity of skin, mucous membranes of the gut and respiratory systems and vascular endothelium
- The occurrence of chronic and acute inflammatory processes
Tissue and organ damage - The glycomics patterns of immune system glycoproteins
From this we propose that:
- Immunofraility is highly complex with multiple causal pathways,
- IF correlates closely with chronic inflammation (cI)
- CI has both systemic and disease-specific components
- Both IF and cI typically rise in phases throughout progression of IBD and other chronic IDs throughout the life course of each individual
- The most vulnerable COVID-19 patients are immunofrail individuals who mount disordered immune responses after SARS-Cov-2 infection due to dysfunctions in their innate and humoral immune systems
If these are true then tracking changes in system and disease-specific cI processes, particularly at early stages of inflammatory episodes, is key to prognosis and prediction of Inflammatory diseases including chronic such as IBD and acute, such as COVID-19. Current biomarkers of inflammation such as hs-CRP and interleukin-6 cannot measure cI because of interference from acute inflammation (aI).
Our Hypothesis
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IF is a complex phenomenon and we propose that measuring it reliably requires a combination of several health markers.
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IF cannot be reliably tracked using existing markers of acute inflammation (aI) but could be monitored by markers of chronic inflammation (cI). To use an analogy, chronic inflammation is like the climate; the changes are slow and small and are difficult to measure. Acute inflammation is like bad weather. We can easily measure it when it is happening. Bad weather masks unfavourable climate change. cI cannot be tracked with current inflammation markers (e.g. hsCRP high sensitivity C Reactive Protein, cytokines, erythrocyte-sedimentation-rate, anti-neutrophil-cytoplasmic-antibodies and regulatory-T-cells) because they measure aI arising from tissue damage.
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Post-translational modifications (PTMs) of immune components in the blood reflect the functional state of the immune system and correlate with cI processes and IF.