Clinical trial NCT06554392: Identification of Serum Level of Glutathione Peroxidase 4
Official title: Identification of Glutathione Peroxidase 4 in Detecting Ferroptosis in Ankylosing Spondylitis and Axial Psoriatic Arthritis Patients .
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Spondyloarthropathy
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2024-08-15
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be selected from AS and axial psoriatic arthritis patients presented sequentially at the outpatient clinic and inpatient unit of the Department of Rheumatology, Rehabilitation and Physical Medicine. Faculty of Medicine .Assiut University.in addition to age and sex matched controls.

Brief summary: * Analysis of the level of glutathione peroxidase 4 (GPX4) in ankylosing spondylitis and axial psoriatic arthritis patients.
* The association of glutathione peroxidase 4 (GPX4) with disease activity and severity in ankylosing spondylitis and axial psoriatic arthritis patients.

Detailed description: Ferroptosis, first reported by Dixon et al. in 2012, is a form of non-apoptotic cell death driven by iron-dependent lipid reactive oxygen species (ROS) and accelerated by the accumulation of lipid peroxides, ultimately leading to oxidative damage to phospholipid membranes and cell death .

Ferroptosis could be induced by iron metabolism disorder, lipid peroxidation accumulation, deficiency of glutathione (GSH) and inactivation of the antioxidant enzyme glutathione peroxidase 4 (GPX4).

The morphological features of ferroptotic cells manifest as an aberrant mitochondrial ultrastructure, including a reduction in mitochondrial volume, an increase in mitochondrial membrane density, and the disappearance of mitochondrial cristae in ferroptotic cells .

Recent studies have increasingly reported on complex associations between ferroptosis and the immune system . The regulatory activity of ferroptosis in immune function and inflammation is multifaceted and involves innate, acquired, and autoimmunity.

Accumulating evidence in recent times has shown an association of ferroptosis with the pathogenesis and development of autoimmune diseases .

Spondyloarthropathy comprises a group of chronic inflammatory rheumatic diseases, including ankylosing spondylitis, reactive arthritis (Reiter syndrome), arthritis or spondylitis associated with inflammatory bowel disease, and psoriatic arthritis, as well as undifferentiated spondyloarthritis. These afflictions predominantly affect the axial skeleton, causing pain and stiffness.

Currently, research on ferroptosis is still in its early stages; therefore, exploring the pathogenesis of ferroptosis and its role in various diseases, and proposing effective and targeted treatment methods have significant theoretical significance and practical value.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed as ankylosing spondylitis according to ASAS criteria . \[13\]
* Patients diagnosed as psoriatic arthritis according to CASPAR criteria. \[14\]
* Age (\>18).

Exclusion Criteria:

* Patient with other autoimmune Rheumatic diseases.
* patients with any of the following conditions: I) severe liver and kidney dysfunction; II) hematopoietic diseases; III) infectious diseases; IV) tumors; or V) other wasting diseases. \[15\]
* patients received certain drugs (for example, sulfasalazine, artemisinin, statins), and experimental reagents (such as erastin) .\[16\]

Primary outcomes:
measure: Analysis of the serum level of glutathione peroxidase 4 (GPX4) in ankylosing spondylitis and axial psoriatic arthritis patients.
timeFrame: baseline
Secondary outcomes:
measure: The association of glutathione peroxidase 4 (GPX4) with disease activity and severity in ankylosing spondylitis and axial psoriatic arthritis patients.
timeFrame: baseline
Other outcomes:
Locations:
Study officials:
affiliation: Rheumatology,Rehabilition,Physical therapy Department ,Assiut university
name: Marwa Abdelaziz, Prof.
role: STUDY_DIRECTOR
affiliation: Rheumatology,Rehabilition,Physical therapy Department ,Assiut university
name: Marwa Galal, Ass. Prof.
role: STUDY_DIRECTOR
affiliation: Rheumatology,Rehabilition,Physical therapy Department ,Assiut university
name: Nesreen Ibrahim, Dr
role: STUDY_DIRECTOR
References:
citation: Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. doi: 10.1016/j.cell.2012.03.042.
citation: Chen R, Zhu S, Zeng L, Wang Q, Sheng Y, Zhou B, Tang D, Kang R. AGER-Mediated Lipid Peroxidation Drives Caspase-11 Inflammasome Activation in Sepsis. Front Immunol. 2019 Aug 8;10:1904. doi: 10.3389/fimmu.2019.01904. eCollection 2019.
citation: Yuan S, Wei C, Liu G, Zhang L, Li J, Li L, Cai S, Fang L. Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1alpha/SLC7A11 pathway. Cell Prolif. 2022 Jan;55(1):e13158. doi: 10.1111/cpr.13158. Epub 2021 Nov 22.
citation: Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, Jiang X. Role of Mitochondria in Ferroptosis. Mol Cell. 2019 Jan 17;73(2):354-363.e3. doi: 10.1016/j.molcel.2018.10.042. Epub 2018 Dec 20.
citation: Chen X, Kang R, Kroemer G, Tang D. Ferroptosis in infection, inflammation, and immunity. J Exp Med. 2021 Jun 7;218(6):e20210518. doi: 10.1084/jem.20210518. Epub 2021 May 12.