TY - JOUR
T1 - Cluster Analysis of Circulating Plasma Biomarkers in Prurigo Nodularis Reveals a Distinct Systemic Inflammatory Signature in African Americans
AU - Sutaria, Nishadh
AU - Alphonse, Martin Prince
AU - Marani, Melika
AU - Parthasarathy, Varsha
AU - Deng, Junwen
AU - Wongvibulsin, Shannon
AU - Williams, Kyle
AU - Roh, Youkyung Sophie
AU - Choi, Justin
AU - Bordeaux, Zachary
AU - Pritchard, Thomas
AU - Dillen, Carly
AU - Semenov, Yevgeniy R.
AU - Kwatra, Madan M.
AU - Archer, Nathan K.
AU - Garza, Luis A.
AU - Dong, Xinzhong
AU - Kang, Sewon
AU - Kwatra, Shawn G.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n = 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n = 9 vs. 33%, n = 3; P = 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P = 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P = 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n = 6 vs. 18%, n = 2; P = 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.
AB - Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n = 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n = 9 vs. 33%, n = 3; P = 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P = 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P = 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n = 6 vs. 18%, n = 2; P = 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.
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U2 - 10.1016/j.jid.2021.10.011
DO - 10.1016/j.jid.2021.10.011
M3 - Article
C2 - 34717952
AN - SCOPUS:85124279104
SN - 0022-202X
VL - 142
SP - 1300-1308.e3
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -