In vivo
|
In vivo
|
In vivo
|
In vivo
|
In vivo
|
In vivo
|
In vivo
|
Skin Prick Test (SPT) |
In situ mast cell degranulation |
Wheal size |
Reduction during therapy |
Reduction during therapy |
No
significant changes |
107,140,160–166 |
Oral Food Challenge (OFC) |
In situ diagnostic test
whereby a specific amount of allergen is ingested in a standardized
setting to note threshold of responsiveness and tolerance. |
Clinical
reactivity upon exposure |
Increase in threshold of tolerated food |
Increase in threshold of tolerated food |
Increase in threshold of
tolerated food |
96,162,167,168 |
Cellular
|
Cellular
|
Cellular
|
Cellular
|
Cellular
|
Cellular
|
Cellular
|
Basophil Activation Test (BAT)
|
Measures FcɛRI cross-linking and basophil activation both by IgE
dependent and independent activation by in vitro exposure of
basophils with extracts or allergens.
May also use a passive sensitization strategy involving basophils from
healthy donors and serum from allergic individuals.
|
%CD63+ positivity, CD 203c expression
Diamine Oxidase (DAO)
|
Reduction of %CD63+ during therapy
|
Reduction of %CD63+ during therapy
|
Transient reduction %CD63+ during therapy
|
15,127,162,163,169–172
|
Mast cell Activation Test (MAT)
|
Mast cells are activated through IgE crosslinking of FcɛRI expressed on
cell surfaces. Measures mast cell activation through in vitro
exposure of mast cells with extracts or allergens. LAD2 or hMCs
(Expressing CD117+)
May also use a passive sensitization strategy involving mast cells from
healthy donors and serum from allergic individuals.
|
%CD63 and
CD107+ positivity
|
N/A
|
N/A
|
N/A
|
173–175
*Indirect evidence used to diagnose IgE-mediated FA.
|
Tregs |
Via IL-10 and TGF- ß release (regulatory cytokines),
directly inhibiting mast cell degranulation and use CTLA-4 and PD-1
mechanisms 72
|
CD4+
CD25+FOXP3+ in whole blood and
isolated PBMCs |
Increased during therapy |
No significant changes |
Induction of LAP1 Tregs *indirect evidence in mice |
112,176,177 |
Th2a |
APCs present allergen to naïve T cells which provoke
differentiation into Th2 responses (Th2a). 178Th2a
increase sIgE, causing IL-4 to prime naïve CD4+ T cells to differentiate
into Th2. |
CD161, CD49d, classical Th2-related surface markers in whole
blood and isolated PBMCs |
Reduction during therapy |
N/A |
N/A |
70,179–181 |
DCregs
|
DCregs produce IL-12, IL-27 and IL-10 skewing immune responses from Th2
to Th1.178
Downregulation of DC2 cell subset and an increase of DCregs support
differentiation of Tregs and Bregs.182
|
C1QA and FCGR3A in whole blood and isolated PBMCs
|
N/A
|
Increased during therapy
|
N/A
|
183,184
|
Bregs |
Br1 cells upregulate IgG4 during their transition to
plasma cells.185 Treg induction via IL-10 and TGF- ß
secretion, direct suppression (IL-10) of Teff and indirect (IL-10) via
DC inhibition.186
|
IL-10 expression and secretion |
Increased during therapy |
N/A |
Increased during treatment |
185,187 *Indirect evidence. |
ILC
Type 2 cytokines
|
ILC2s produce type 2 cytokines (IL-4, IL-5, IL-9, IL-13). Common
alarmins recruit ILC2s to release proinflammatory cytokines.
Antagonization of Th2 responses because of successful AIT.
|
N/A
IL-4, IL-5, IL-9, IL-13 in whole blood and isolated PBMCs
Il-33
|
N/A
Reduction during therapy
|
Reduction during therapy
Reduction during therapy
|
N/A
Tendency to decrease, however not significant during therapy
|
65,188
163,176,189
|
Tfh13 cells
|
Subset of Th cell found in B-cell follicles that controls antibody
isotypes switching, affinity maturation and B-cell memory.
|
CXCR5, PD-1, Bcl-6, Il-21
|
N/A
|
N/A
|
N/A
|
190
*Continuous allergen exposure blocks CXCR5 expression in memory Tfh
cells.
|
Antibody based
|
Antibody based
|
Antibody based
|
Antibody based
|
Antibody based
|
Antibody based
|
Antibody based
|
Allergen and specific IgE (sIgE)
|
Culprit molecule of IgE mediated allergy. Binds to high-affinity IgE
receptor FcɛRI on surfaces of mast cells, basophils and eosinophils,
some sub-types of APCs and via the low affinity IgE receptor
FcɛRII.
|
Extract-specific IgE
Allergen-specific IgE
|
Transient increase, then decrease throughout therapy
|
Transient increase, then decrease throughout therapy
|
Decrease in late phase of therapy
|
107,113,191–196,114,127,160,162,164–166,170
|
sIgG4
|
Soluble IgG4 directly interacts with allergens, membrane-bound IgG4
interferes with allergen-mediated IgE crosslinking and inhibits mast
cells activation and basophil degranulation.
|
Extract-specific IgG4
Allergen-specific IgG4
|
Increase during therapy
|
Increase during therapy
|
Increase during therapy
|
113,127,191,197,198,140,160,162,164–166,170,176
|
sIgA
|
Tregs (Tr1) secrete IL-10 and TGF-ß to induce class-switch and promote
IgG4, IgA production.104 Similar to IgG4, IgA may act
specifically at the level of mucosal surfaces.
|
Extract-specific IgG4
Allergen-specific IgG4
|
Increase during treatment
|
Increased during treatment
|
N/A
|
108,194,199,200
|