The WES showed PRF1
compound heterozygous mutations of c.1349G>A (p.T450M) and c.218C>T (p.C73Y), inherited from his father and mother, respectively.
11 MeDEGs were confirmed to be differentially expressed in SSc (p<0.05), including seven upregulated genes (CSTA, CTSG, C3AR1, PLAUR, LTBR, ODF3B, and ELANE) and four downregulated genes (CXCR6, PAG1, RUNX3, and PRF1) (Figure 4).
Several genes were downregulated and hypermethylated in PBMC of SSc, including F2R, CXCR6, PAG1, PRF1, and RUNX3.
Characterisation of diverse PRF1
mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis.
Cluster analysis revealed that a limited set of genomic classifiers (14 genes including IL-1RAP, GAS1, PRF1
, TMEM158, and IL-2R) could distinguish ALCL from PTCL-NOS and normal T cells, regardless of ALK status.
HLH-related genes (including AP3B1, FASLG, PRF1
, TNFRSF1A, BIRC4, ITK, RAB27A, UNC13D, CASP10, ITPKC, SH2D1A, CD27, LYST, STX11, FAS, MAGT1 and STXBP2) were detected with high-throughput sequencing.
Recent data suggest an association between radiographic damage and polymorphisms of genes encoding TNF, IL-1, IL-6, IL-4, IL-5, OPN, and PRF1
The diagnosis is made with either the presence of molecular aberrations consistent with HLH, for example, pathologic mutations in PRF1
, UNC13D, or STX11, or with fulfilment of five of eight clinical criteria outlined above.
We also evaluated T cell- and NK cell-related genes, including CD3D [CD3d molecule, delta (CD3-TCR complex)], CD69 (CD69 molecule), PRF1
[perforin 1 (pore forming protein)], GNLY (granulysin), CCR3 [chemokine (C-C motif) receptor 3], KLRK1 (killer cell lectin-like receptor subfamily K, member 1), IDO1 (indoleamine 2,3-dioxygenase 1), and KLRD1 (CD94) (killer cell lectin-like receptor subfamily D, member 1).
After that, 100 [micro]l of cell culture fluid from each well was collected, duplicates were pooled, redivided into two 100 [micro]l aliquots, and subjected to analysis by sandwich ELISA for granzyme B (DuoSet Development kit; R&D Systems Europe Ltd.) and perforin (PRF1
; Holzel Diagnostika Handels GmbH, Germany).
Characterization of PRF1
, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis.