Table 4.
Mediators of the EBA effector phase.
| Target | Function | References |
|---|---|---|
| C5 | C5-deficient mice are partially or completely protected from EBA inducing by antibody transfer | (201, 211) |
| C1q/factor B | Respective knock-out mice are partially protected from EBA inducing by antibody transfer | (203) |
| IgG glycosylation | Enzymatic removal of terminal IgG N-glycosylation renders anti-COL7 antibodies non-pathogenic in antibody transfer-induced EBA | (192, 193) |
| Galactosylated IgG | Immune complexes with highly galactosylated immune complexes inhibit pro-inflammatory signaling of the C5aR1 through dectin-1 and Fc gamma receptor IIB, resulting in a protection from antibody transfer-induced EBA | (202) |
| IL-6 | In antibody transfer-induced EBA, IL-6 has anti-inflammatory effects, through up-regulation of IL-1ra | (209) |
| CXCR-1/2 | Blockade of the CXCR-1/2 ligands impairs induction of EBA by antibody transfer and slows disease progression when applied in therapeutic settings in immunization-induced EBA | (212) |
| GM-CSF | Blockade of GM-CSF impairs induction of EBA by antibody transfer and slows disease progression when applied in therapeutic settings in immunization-induced EBA | (177) |
| IL-1/IL-1ra | Both anti-IL1β or IL-1ra (anakinra) treatment impair the induction of EBA by antibody transfer. Additionally, anakinra halts disease progression when applied therapeutically in immunization-induced EBA | (213) |
| TNFa | Blockade of TNF impairs induction of EBA by antibody transfer and halts disease progression when applied in therapeutic settings in immunization-induced EBA | (214) |
| LTB4 | Blockade of either LTB4 biosynthesis or its' receptor completely protects mice from EBA induction by antibody transfer | (208) |
| IL-17A/E | IL17R-deficient mice are partially protected from EBA inducing by antibody transfer | (215) |
| NADPH oxidase | Neutrophil cytosolic factor 1-deficient mice, lacking functional NADPH oxidase, -deficient mice are completely protected from EBA inducing by antibody transfer | (216) |
| Elastase | Elastase is required for the induction of subepidermal blisters ex vivo | (217) |
| Flii | Blockade of Flii protects mice from EBA induction by antibody transfer | (218–220) |
| MIP1α | Increased expression, but no effect on clinical phenotype | (221) |
| S100 | Increased expression, but no effect on clinical phenotype | (222) |
| Trem1 | Increased expression, but no effect on clinical phenotype | (223) |
C, complement factor; IgG, immunoglobulin G; IL, interleukin; COL7, type VII collagen; CXCR, CXC-chemokin receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; TNF, tumor necrosis factor; LTB, leukotriene; NADPH, nicotinamide adenine dinucleotide phosphate; Flii, flightless I; MIP1α, macrophage inflammatory protein1α; Trem1, Triggering receptor expressed on myeloid cells-1.