# CASP8 and CASP3 mRNA Expression in Autoimmune Lymphoproliferative Syndrome (ALPS) and Chronic Immune Thrombocytopenia (ITP)

**Authors:** Anna Pau, Federico Rondot, Stefano Gambarino, Anna Clemente, Cristina Calvi, Paola Montanari, Ilaria Galliano, Massimiliano Bergallo

PMC · DOI: 10.3390/genes17020206 · Genes · 2026-02-09

## TL;DR

This study compares CASP8 and CASP3 gene expression in blood from patients with ALPS, ITP, and healthy individuals, finding distinct and shared patterns.

## Contribution

The study reveals distinct CASP8 and shared CASP3 mRNA upregulation in ALPS and chronic ITP compared to healthy controls.

## Key findings

- CASP8 mRNA is significantly higher in ALPS and ITP patients than in healthy controls.
- CASP3 mRNA is elevated in both ALPS and ITP patients compared to controls.
- ALPS patients show lower CASP8 expression than ITP patients.

## Abstract

Background: Fas/FasL-mediated apoptosis is central to immune homeostasis and is implicated in autoimmune lymphoproliferative syndrome (ALPS) and immune thrombocytopenia (ITP). We aimed to compare whole-blood transcriptional levels of CASP8 and CASP3 across ALPS, chronic ITP, and healthy controls. Methods: CASP8 and CASP3 mRNA expression was quantified by real-time PCR in whole blood from clinically diagnosed ALPS patients, chronic ITP patients, and healthy controls. Results: CASP8 mRNA expression was significantly increased in ALPS and ITP versus controls (p = 0.0009 and p < 0.0001, respectively) and was lower in ALPS than in ITP (p = 0.0265). CASP3 mRNA was also increased in both patient groups versus controls (ALPS: p = 0.0045; ITP: p < 0.0001), with no significant difference between ALPS and ITP (p = 0.1692). Conclusions: ALPS and chronic ITP show distinct CASP8 transcriptional patterns and a shared upregulation of CASP3 at the whole-blood mRNA level. These findings are descriptive and do not directly assess caspase activation or apoptotic pathway activity; further protein- and cell subset-based studies are needed to clarify functional implications.

## Linked entities

- **Genes:** CASP8 (caspase 8) [NCBI Gene 841], CASP3 (caspase 3) [NCBI Gene 836]
- **Diseases:** Autoimmune Lymphoproliferative Syndrome (MONDO:0011158)

## Full-text entities

- **Genes:** CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CASP10 (caspase 10) [NCBI Gene 843] {aka ALPS2, FLICE-2, FLICE2, MCH4}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** lymphadenopathy (MESH:D008206), autoimmune cytopenias (MESH:D001327), splenomegaly (MESH:D013163), neurological diseases (MESH:D020271), impaired platelet production (MESH:D001606), injury to (MESH:D014947), autoimmune or inflammatory disorders (MESH:D007249), cancer (MESH:D009369), ALPS (MESH:D056735), lymphomas (MESH:D008223), ITP (MESH:D016553), platelet destruction (MESH:D008105), cytopenias (MESH:D006402), Evans syndrome (MESH:C536380), infections (MESH:D007239), thrombocytopenia (MESH:D013921)
- **Chemicals:** water (MESH:D014867), mycophenolate mofetil (MESH:D009173), MgCl2 (MESH:D015636), EDTA (MESH:D004492), sirolimus (MESH:D020123), dd (MESH:C007792), Improm-II (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

23 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940764/full.md

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Source: https://tomesphere.com/paper/PMC12940764