according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,”, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in . “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.