Genes involved in platelet aggregation and activation are downregulated during acute anaphylaxis in humans.

OBJECTIVE: Mechanisms underlying the anaphylactic reaction in humans are not fully understood. Here, we aimed at improving our understanding of anaphylaxis by investigating gene expression changes.

METHODS: Microarray data set GSE69063 was analysed, describing emergency department (ED) patients with severe anaphylaxis ( n = 12), moderate anaphylaxis ( n = 6), sepsis ( n = 20) and trauma ( n = 11). Samples were taken at ED presentation (T0) and 1 h later (T1). Healthy controls were age and sex matched to ED patient groups. Gene expression changes were determined using limma , and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients ( n = 31) and matched healthy controls ( n = 10), using quantitative reverse transcription-polymerase chain reaction.

RESULTS: Platelet aggregation was dysregulated in severe anaphylaxis at T0, but not in moderate anaphylaxis, sepsis or trauma. Dysregulation was not observed in patients who received adrenaline before T0. Seven genes ( GATA1 (adjusted P- value = 5.57 × 10-4 ), TLN1 (adjusted P- value = 9.40 × 10-4 ), GP1BA (adjusted P -value = 2.15 × 10-2 ), SELP (adjusted P -value = 2.29 × 10-2 ), MPL (adjusted P -value = 1.20 × 10-2 ), F13A1 (adjusted P -value = 1.39 × 10-2 ) and SPARC (adjusted P -value = 4.06 × 10-2 )) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene ( TLN1 (adjusted P -value = 1.29 × 10-2 )) was significantly downregulated in moderate anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls.

CONCLUSION: Downregulation of genes involved in platelet aggregation and activation is a unique feature of the early anaphylactic reaction not previously reported and may be associated with reaction severity.