Immune Dysregulation and Metabolic Syndrome Closely Related, Study Suggests

Metabolic syndrome (MetS) is highly associated with immune dysregulation, evidenced by reduced FOXP3+ expression in patients with psoriasis, according to a recent cross-sectional study.

MetS is a well-known comorbidity of psoriasis, appearing twice as often in patients with psoriasis compared with controls in previous studies. The condition often appears as hyperlipidemia, hypertension, coronary artery disease, type 2 diabetes, and increased body mass index (BMI).2

“This study aims to investigate the impact of MetS on immune regulation, psoriasis severity, flare frequency, and QoL in patients with psoriasis,” wrote Flora Ramona Sigit Prakoeswa, MD, MPH, department of dermatology, venerology, and aesthetic, Universitas Muhammadiyah, and colleagues. “Focusing on the expression levels of key cytokines such as IL-17, IL-23, and FOXP3+, this research seeks to uncover potential immunological mechanisms that could inform future personalized treatment strategies.”1

Investigators initially included 50 patients, divided into 2 groups: those with and without MetS. However, challenges with data collection resulted in a final total of 42 patients with psoriasis, with 13 in the psoriasis with MetS (Pso-MetS) group and 29 in the psoriasis group. Inclusion criteria were patients ≥18 years of age currently receiving standard psoriasis therapy, such as topical corticosteroids, systemic treatments, or phototherapy. Patients with other autoimmune comorbidities or terminal illnesses were excluded.1

MetS was diagnosed if ≥3 of the following criteria were met:

• Central obesity (waist circumference >102 cm in men or >88 cm in women)
• Hypertension (blood pressure >130/85 mmHg)
• Fasting blood glucose (FBG) ≥100 mg/dL
• Plasma triglycerides ≥150 mg/dL
• Low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women).1

Psoriasis severity was measured via the Psoriasis Area and Severity Index (PASI). Flare frequency was recorded based on patient history over the past year. Psoriasis’s impact on patient QoL was measured using the Dermatology Life Quality Index (DLQI).1

Investigators noted patients in the Pso-MetS group were significantly older than those in the psoriasis group (56.5 +/- 11.5 versus 41.3 +/- 12.6 years; P = .003). Systolic blood pressure was also greater in the Pso-MetS group (154.3 +/- 18.97 mmHg versus 124.9 +/- 17.73 mmHg; P <.001), while diastolic showed no significant difference.1

Fasting blood glucose (137.08 +/- 64.97 mg/dL versus 82.03 +/- 9.44 mg/dL; P = .002) and triglyceride (263.92 +/- 173.67 mg/dL versus 110.89 +/- 32.3 mg/dL; P <.001) were also higher in the Pso-MetS group. However, HDL levels were lower in the Pso-MetS group (46.46 +/- 6.91 mg/dL) than the psoriasis group (53.1 +/- 32.3 mg/dL; P = .004).1

Investigators noted FOXP3+ expression was lower in the Pso-MetS group (.027 +/- .02) compared to the psoriasis group (.064 +/- .067; P = .022). However, no differences were found in IL-17 or IL-23. Investigators attributed this lack of significance to a small sample size. No significant differences were found between the 2 groups in PASI or DLQI scores (P = .99 and P = .095, respectively).1

Ultimately, based on the data Prakoeswa and colleagues highlight the potential of FOXP3+ as not only a biomarker of immune imbalance but also as a potential therapeutic target. Given its relation to Treg activity, enhancing its expression could offer dual benefits in controlling cutaneous and metabolic inflammation.1

However, given the small sample size, the team encourages further research into the relationship between psoriasis and MetS.

“Due to the small and uneven sample sizes between groups, the results—especially regarding treatment responses—were analyzed descriptively,” Prakoeswa and colleagues wrote. “Future studies with larger, balanced cohorts and longitudinal designs are warranted to better understand the immunometabolic connections in psoriasis and to identify potential therapeutic targets.”1

References

1. Prakoeswa FR, Maharani F, Hidayat S, et al. The impact of metabolic syndrome on Immune Regulation (IL‐17, IL‐23, and foxp3+), psoriasis severity, flare frequency, and quality of life in psoriasis patients: A cross‐sectional study. International Journal of Inflammation. 2025;2025(1). doi:10.1155/ijin/5855171

2. Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20(6):1475. Published 2019 Mar 23. doi:10.3390/ijms20061475