“…from left to right are the lower extremities, the upper extremities, the trunk to the head and neck, leaving the head and neck distant from the other three regions. This finding is consistent with the recent view that head and neck erythema is a prominent form of AD 29 , 30 . Fig.…”
Section: Resultssupporting
confidence: 93%
“…All the patients included in two analyses were treated according to the Japanese guideline for atopic dermatitis 54 , such as emollients, topical corticosteroids and/or tacrolimus, oral antihistamines and immunosuppressants 29 . Note that the use of antihistamines was recommended as an adjuvant therapy to anti-inflammatory topical therapy to reduce itchiness in the treatment policy proposed by the Japanese guideline at the moment (i.e.…”
Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.
“…from left to right are the lower extremities, the upper extremities, the trunk to the head and neck, leaving the head and neck distant from the other three regions. This finding is consistent with the recent view that head and neck erythema is a prominent form of AD 29 , 30 . Fig.…”
Section: Resultssupporting
confidence: 93%
“…All the patients included in two analyses were treated according to the Japanese guideline for atopic dermatitis 54 , such as emollients, topical corticosteroids and/or tacrolimus, oral antihistamines and immunosuppressants 29 . Note that the use of antihistamines was recommended as an adjuvant therapy to anti-inflammatory topical therapy to reduce itchiness in the treatment policy proposed by the Japanese guideline at the moment (i.e.…”
Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.
“…Regarding WHO region, 59% (13/22) of studies was performed in the Western Pacific Region and 41% (9/22) in Region of the Americas and/or the European Region. Thirteen studies investigated genetic characteristics, 105 , 108 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 and eight studies investigated serum markers and other characteristics 14 , 15 , 22 , 45 , 46 , 101 , 161 , 162 (see Table S1 c and Appendix S3 , Supporting Information).…”
Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital‐based (59%, 109/186) and cross‐sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data‐driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety‐one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty‐six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.
“…Through its enzymatic activity, TYMP produces 2-deoxy-d-ribose-1-phosphate from thymidine; subsequent hydrolysis generates 2-deoxy-d-ribose, which is the molecule that exerts chemotactic and angiogenic effects ( 31 ). A clinical study identified PSAPL1 genes to be enriched in the patients with face and neck atopic dermatitis(AD), suggesting that innate immune system is potentially associated with the pathophysiology of face and neck AD ( 32 ). PSAPL1 was associated with breast cancer grade and involved in the epithelial cell differentiation pathways and the sphingolipid metabolic process ( 33 ).…”
Proliferative diabetic retinopathy (PDR) accounts for severe impact on vision, its mechanism is still poorly understood. To compare the differences of vitreous protein profiles in PDR patients before and after a complete anti-vascular endothelial growth factor (VEGF) loading dose with ranibizumab treatment. Twelve vitreous humor (VH) samples were collected from six PDR patients before (set as pre group) and after (set as post group) intravitreal injection of ranibizumab (IVR) treatment. LC–MS/MS and bioinformatics analysis were performed to identify differentially expressed proteins. Proteins were validated with targeted proteomics using parallel reaction monitoring (PRM) in a validation set consisting of samples from the above patients. A total of 2680 vitreous proteins were identified. Differentially expressed proteins were filtrated with fold change ≥2.0 (post group/ pre group protein abundance ratio ≥2 or ≤ 0.5) and p-value <0.05. 11 proteins were up-regulated and 17 proteins were down-regulated, while consistent presence/absence expression profile group contains one elevated protein and nine reduced proteins, among which seven proteins were identified as potential biomarkers for IVR treatment through PRM assays. Bioinformatics analysis indicated the up-regulated proteins were significantly enriched in “GnRH secretion” and “Circadian rhythm” signaling pathway. This report represents the first description of combined label-free quantitative proteomics and PRM analysis of targeted proteins for discovery of different proteins before and after IVR treatment in the same patient. IVR treatment may protect against PDR by promoting SPP1 expression through “GnRH secretion” and “Circadian rhythm” signaling pathway.
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