Table 4.
Clustering of selected markers according to clinical relevance and involvement of immune function(s)
| Markers of immune function linked to | ||||
| Classification | Defence against pathogens | Avoidance or mitigation of hypersensitivity (e.g. allergy) | Inflammation control (reduction of low-grade metabolic inflammation) | |
| Group A marker | Indicative of clinical relevance and involvement of immune function(s) | Pathogen-specific immune response (specific antibodies and specific T-cell response after natural or experimental infection) | Specific response or symptoms after an experimental allergen challenge (skin, labial, respiratory or oral provocation tests) | NA |
| Vaccine-specific immune response (seroprotection, seroconversion, specific antibodies and specific T cells) | Basophil activation test | |||
| Specific DTH or CHS response | Tryptase in plasma | |||
| Mucosal IgA (in saliva, tears, etc.) | Allergen-specific IgE (sIgE)* | |||
| Group B marker | Indicative of clinical relevance but not necessarily of the involvement of immune function(s) (i.e. clinical symptom) | Symptoms of infection (incidence, duration and severity after natural or experimental infection) | Symptoms of allergy (rhinitis, asthma, urticaria, eczema, GI manifestations, etc.) | Symptoms associated with low-grade inflammation (e.g. insulin resistance and blood pressure) |
| Pathogen load | Response to general food provocation | |||
| Group C marker | Indicative of the involvement of immune function(s) and associated with clinical relevance in specific (sub)populations | Ex vivo (pathogen-specific) B-cell function | Allergen-specific IgE (sIgE)* | In vivo response to a pro-inflammatory challenge |
| Ex vivo (pathogen-specific) T-cell function | Ex vivo (allergen-specific) Th1/Th2-cell function | Markers of acute-phase response (CRP, TNF, IL-1, IL-6 and blood sedimentation) | ||
| Ex vivo phagocyte function | Ex vivo (allergen-induced) production of Th1/Th2 mediators | (Ratio of) pro- and anti-inflammatory mediators | ||
| Ex vivo NK-cell function | Ex vivo Treg-cell function | Ex vivo Th1/Th17/Treg-cell function | ||
| Migration of Langerhans cells | Ex vivo APC function | Ex vivo oxidative burst | ||
| Group D marker | Provides mechanistic insights but not necessarily into clinical relevance (non-exhaustive list of examples) | Markers of acute-phase response (CRP, TNF, IL-1, IL-6 and blood sedimentation) | Markers of acute-phase response (CRP, TNF, IL-1, IL-6 and blood sedimentation) | Plasma adiponectin and leptin |
| (Ratio of) pro- and anti-inflammatory mediators | (Ratio of) pro- and anti-inflammatory mediators | Plasma endotoxin (LPS) | ||
| Percentage of subsets including CD4:CD8 ratio | Total IgE | Plasma and faecal calprotectin | ||
| Circulating or ex vivo-produced antibodies (not antigen- or vaccine-specific) | Circulating cytokines | |||
| Circulating or ex vivo-produced cytokines | Plasma and faecal calprotectin |
NA, not applicable; DTH, delayed-type hypersensitivity; CHS, contact hypersensitivity; sIgE, specific IgE; GI, gastrointestinal; Th, T helper; CRP, C-reactive protein; NK, natural killer; Treg, regulatory T cell; APC, antigen-presenting cells; LPS, lipopolysaccharide.
sIgE clearly indicates the involvement of immune function, but in the absence of concurrent clinical assessment, its relevance is controversial. Some see it as a clinically relevant marker also used to guide therapy, whereas others (including the European Food Safety Authority) emphasise that not all allergic subjects have sIgE, not all subjects with sIgE have allergic symptoms and changes in sIgE are not always associated with changes in symptoms.