Interleukin-13, Periostin Show Potential as Biomarkers in Prurigo Nodularis

The elevated levels of interleukin-13 (IL-13) and the protein periostin seen in the whole blood samples taken from patients who had uncontrolled prurigo nodularis (PN) compared with a group of healthy controls may hold potential as indicators of type 2 inflammation in PN, according to new study findings published in Frontiers in Medicine.

In addition to IL-13 and periostin, the blood plasma was also analyzed for levels of IL-4, IL-5, and immunoglobulin E (IgE), with analysis of variance (ANOVA) used by the study investigators for statistical analysis.

“The role of type 2 inflammation is of interest in PN, given that there have been several off-label reports of the efficacy of treatment response with dupilumab, an IL-4 receptor α inhibitor that prevents IL-4 and IL-13 signaling,” the study authors wrote. “There is also preliminary evidence of disease heterogeneity in clinical presentation and systemic inflammation, with suggestions of neural- and immune-biased disease endotypes.”

The 47 patients in the study were under the care of Johns Hopkins Dermatology, and the patients who had uncontrolled PN had to have uncontrolled disease for at least 6 weeks before study entry, which was defined as “a Worst Itch Numeric Rating Scale score of ≥ 7 out of 10 points and nodule count of ≥ 20 nodules,” the investigators wrote. There were 29 patients in the PN cohort (mean [SD] age, 53.8 [13.4] years) and 18 controls (mean age, 52.2 [13.2] years), 72% of each group comprised female patients, and 69% and 67%, respectively, were identified as being of Black or African American race.

At baseline, the PN group had a mean (SD) Worst Itch Numeric Rating Scale score of 8.9 (1.3) and an Investigator’s Global Assessment score of 3.3 (0.6). Both scores were 0.0 for the control group. Twenty-four percent of the PN group also had concomitant atopic dermatitis.

Following use of single-plex assays on the extracted blood samples, the levels of IL-13 and periostin were shown to be significantly elevated in the group with uncontrolled PN:

• IL-13: 0.13 vs 0.006 pg/mL (P = .0008)
• Periostin: 80.3 vs 60.2 ng/mL (P = .012)

In addition, the level of IgE in the study group was determined to be “approaching significance,” at 1202.0 compared with 432.7 ng/mL in the control group (P = .08). However, levels of IL-4 and IL-5 were not significantly elevated between the PN and control groups, respectively:

• IL-4: 0.11 vs 0.02 ng/mL (P = .30)
• IL-5: 0.75 vs 0.40 ng/mL (P = .10)

A separate clustering analysis, in which cluster 1 had 18 patients with PN and 18 controls and cluster 2 had 11 patients with PN, produced higher overall levels of IL-13 and IL-5 in cluster 2: 0.33 vs 0.008 ng/mL (P = .0001) and 1.22 vs 0.43 (P = .03), respectively. In addition, when comparing only the patients with PN from cluster 1 with cluster 2, the latter again had higher levels of IL-13: 0.33 vs 0.007 pg/mL (P = .0003). Biomarkers did not differ significantly between the patient groups in cluster 1.

“Previous studies have suggested endotypes in PN, represented by varying degrees of circulating inflammatory biomarkers across varying immune axes, including plasma IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α,” the study investigators noted. “Our findings provide further evidence of distinct endotypes in PN with respect to type 2 inflammation.”

The added that identifying these distinctive endotypes and their various inflammatory signaling “may help explain varying differences in phenotypic presentation observed between patients,” but that because of the disease’s heterogeneity, additional biomarker studies are needed.

Reference

Parthasarathy V, Cravero K, Deng J, et al. Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: a cluster analysis. Front Med (Lausanne). Published online December 6, 2022. doi:10.3389/fmed.2022.1011142