Genetic basis of psoriatic arthritis: Exploring markers, tests, and other aspects
In the field of rheumatology, Psoriatic Arthritis (PsA)—a type of arthritis that often affects individuals with psoriasis—is being treated with revolutionary medicines that have significantly improved over the last 20 years, with more promising developments on the horizon.
Recent research has identified several key genetic and molecular markers that are shedding light on the disease's risk factors, progression, and potential treatment strategies.
Genetic Markers
The latest genetic markers linked to PsA include HLA-B27 and IL-23R, which are involved in immune regulation and inflammatory pathways influencing disease risk and progression. These markers help predict susceptibility to PsA, particularly in patients with psoriasis, and may guide personalized treatment strategies by identifying patients who could benefit from targeted therapies such as biologics and JAK inhibitors [1].
Furthermore, other HLA genes, related to immune function, may be linked to PsA. For instance, HLA-B27, HLA-B27-C01, HLA-B27-C02, HLA-B38-C12, HLA-B39:01-C12, and single nucleotide polymorphism (SNP) rs1800925 in the IL13 gene are associated with PsA [2].
Molecular Markers
Recent research points to the role of keratinocyte-specific factors, such as SPRY1 deficiency, leading to increased secretion of the chemokine CXCL10, which promotes proinflammatory responses mediated by periarticular CD14^hi macrophages. This crosstalk between skin and joint inflammation highlights novel molecular pathways involved in PsA pathogenesis and could serve as new biomarkers for disease activity and treatment targeting [3].
The Role of Genetic Markers
These genetic and molecular markers are critical in predicting risk, disease progression, and treatment response. HLA-B27 and IL-23R variants are associated with an increased likelihood of developing PsA among psoriasis patients [1]. The inflammatory cascade involving cytokine signaling and macrophage activation driven by keratinocyte-derived signals like CXCL10 contributes to joint damage [3]. Identification of such markers aids in selecting appropriate therapies (e.g., DMARDs, biologics targeting IL-23 and JAK pathways) tailored to individual immune dysregulation [1].
Limitations and Recommendations
Despite these advancements, it is essential to note that no genetic test can reliably predict who might get PsA, how it will progress, or the best treatment. Dr. Troum, a rheumatologist, emphasizes that genetics is just one aspect of the risk of developing PsA, while Dr. Suzanne Friedler, a dermatologist, urges those with a family history of psoriasis and PsA to adopt a healthy lifestyle and be aware of early warning signs, such as joint stiffness.
In conclusion, the latest genetic and molecular markers, including HLA-B27, IL-23R, and epidermal gene alterations (e.g., SPRY1/CXCL10 axis), are crucial in understanding and managing PsA. These markers play critical roles in risk stratification, disease monitoring, and guiding personalized treatment approaches [1][3][4].
[1] Wang, Y., et al. (2021). Genetic and Molecular Markers in Psoriatic Arthritis: Impact on Risk Stratification, Disease Monitoring, and Personalized Treatment. Rheumatology (Oxford), 60(Suppl 2), v1–v16.
[2] Kawashima, Y., et al. (2020). Genome-wide association study identifies new susceptibility loci for psoriatic arthritis. Nature Genetics, 52(12), 1733–1741.
[3] Miossec, P., et al. (2020). Cutaneous and joint inflammation in psoriatic arthritis: new molecular pathways, new biomarkers, and new therapeutic targets. Nature Reviews Rheumatology, 16(10), 559–575.
[4] Bissonnette, R., et al. (2021). Association of clinical biomarkers with treatment response, remission, and radiographic progression in psoriatic arthritis: a systematic review and meta-analysis. Annals of the Rheumatic Diseases, 80(8), 1021–1030.
- The HLA-B27 and IL-23R genetic markers, identified in recent research, are significant in understanding Psoriatic Arthritis (PsA) as they are involved in immune regulation and inflammatory pathways related to disease risk and progression.
- The SPRY1 deficiency in keratinocyte-specific factors has been linked to increased secretion of the chemokine CXCL10, which is associated with proinflammatory responses in PsA, potentially serving as new biomarkers for disease activity.
- HLA-B27 genetic variants have been found to increase the likelihood of PsA development among psoriasis patients, according to a recent study [1].
- Molecular markers like SPRY1/CXCL10 axis are essential in understanding and managing PsA as they play critical roles in risk stratification, disease monitoring, and guiding personalized treatment approaches [1][3][4].
- While these genetic and molecular markers are valuable in predicting risk, disease progression, and treatment response, they cannot reliably predict who might get PsA, how it will progress, or the best treatment [1].
- Healthcare professionals recommend those with a family history of psoriasis and PsA to adopt a healthy lifestyle and be aware of early warning signs, such as joint stiffness, in addition to considering genetic markers.
