Merge pull request #369 from monarch-initiative/pr/atopic-dermatitis-beta-thalassemia-curation

Add curated Atopic Dermatitis and Beta Thalassemia disorder entries

Author: cmungall

kb/disorders/Atopic_Dermatitis.yaml

@@ -0,0 +1,395 @@
+name: Atopic Dermatitis
+category: Complex
+parents:
+- Dermatological Disease
+- Chronic Inflammatory Disease
+- Allergic Disease
+has_subtypes:
+- name: Early-Onset Atopic Dermatitis
+  description: Onset in infancy or early childhood, often associated with the 
+    atopic march progressing to asthma and allergic rhinitis.
+- name: Adult-Onset Atopic Dermatitis
+  description: First presentation in adulthood, often with different clinical 
+    distribution and associations compared to childhood-onset disease.
+- name: Extrinsic Atopic Dermatitis
+  description: Associated with IgE-mediated sensitization to environmental 
+    allergens. Elevated serum IgE and positive skin prick tests.
+- name: Intrinsic Atopic Dermatitis
+  description: Without IgE-mediated sensitization. Normal serum IgE levels. 
+    Represents approximately 20% of cases.
+pathophysiology:
+- name: Epidermal Barrier Dysfunction
+  description: Loss-of-function mutations in filaggrin (FLG) and other barrier 
+    proteins lead to impaired skin barrier integrity, increased transepidermal 
+    water loss, and enhanced allergen penetration. This is the primary 
+    initiating event in many patients.
+  genes:
+  - preferred_term: FLG
+    term:
+      id: hgnc:3748
+      label: FLG
+  biological_processes:
+  - preferred_term: Keratinization
+    term:
+      id: GO:0031424
+      label: keratinization
+  cell_types:
+  - preferred_term: Keratinocyte
+    term:
+      id: CL:0000312
+      label: keratinocyte
+  evidence:
+  - reference: PMID:16550169
+    supports: SUPPORT
+    evidence_source: HUMAN_CLINICAL
+    snippet: Filaggrin is a key protein that facilitates terminal
+      differentiation of the epidermis and formation of the skin barrier. Here
+      we show that two independent loss-of-function genetic variants (R510X
+      [sic, correct designation is R501X] and 2282del4) in the gene encoding
+      filaggrin (FLG) are very strong predisposing factors for atopic
+      dermatitis.
+    explanation: Landmark study establishing FLG loss-of-function as the
+      strongest genetic risk factor for atopic dermatitis, with ~9% carrier
+      frequency in Europeans.
+  - reference: PMID:21388665
+    supports: PARTIAL
+    evidence_source: HUMAN_CLINICAL
+    snippet: They are similar in that they are complex inherited diseases
+      involving genes that encode immune components and structural proteins that
+      regulate differentiation of epidermal cells. Each disease is characterized
+      by proliferation of epidermal keratinocytes and abnormal cornification or
+      terminal differentiation in the epidermis
+    explanation: Describes the epidermal barrier dysfunction in atopic
+      dermatitis including abnormal cornification and keratinocyte
+      differentiation.
+- name: Type 2 Immune Response
+  description: Th2-skewed immune response drives the hallmark inflammation. 
+    IL-4, IL-13, and IL-31 promote IgE production, eosinophil recruitment, and 
+    pruritus. IL-4/IL-13 signaling through JAK1/STAT6 further impairs barrier 
+    function by downregulating filaggrin and other barrier proteins.
+  genes:
+  - preferred_term: IL4
+    term:
+      id: hgnc:6014
+      label: IL4
+  - preferred_term: IL13
+    term:
+      id: hgnc:5973
+      label: IL13
+  - preferred_term: IL31
+    term:
+      id: hgnc:19372
+      label: IL31
+  - preferred_term: STAT6
+    term:
+      id: hgnc:11368
+      label: STAT6
+  downstream:
+  - target: Epidermal Barrier Dysfunction
+    description: IL-4 and IL-13 downregulate filaggrin expression, creating a 
+      vicious cycle of barrier disruption and immune activation.
+  - target: Pruritogen-Induced Neuronal Activation
+    description: IL-31 signaling contributes to neuronal itch signaling in 
+      lesional skin.
+  biological_processes:
+  - preferred_term: Type 2 immune response
+    term:
+      id: GO:0042092
+      label: type 2 immune response
+  - preferred_term: T-helper 2 cell differentiation
+    term:
+      id: GO:0045064
+      label: T-helper 2 cell differentiation
+  - preferred_term: Interleukin-4-mediated signaling pathway
+    term:
+      id: GO:0035771
+      label: interleukin-4-mediated signaling pathway
+  - preferred_term: IgE isotype switching
+    term:
+      id: GO:0035708
+      label: interleukin-4-dependent isotype switching to IgE isotypes
+  cell_types:
+  - preferred_term: T-helper 2 cell
+    term:
+      id: CL:0000546
+      label: T-helper 2 cell
+  - preferred_term: Group 2 innate lymphoid cell
+    term:
+      id: CL:0001069
+      label: group 2 innate lymphoid cell
+  - preferred_term: Eosinophil
+    term:
+      id: CL:0000771
+      label: eosinophil
+  - preferred_term: Mast cell
+    term:
+      id: CL:0000097
+      label: mast cell
+  evidence:
+  - reference: PMID:30819278
+    supports: SUPPORT
+    evidence_source: HUMAN_CLINICAL
+    snippet: Type 2 cytokines as well as interleukin 17 and interleukin 22
+      contribute to skin barrier dysfunction and the development of AD.
+    explanation: Confirms the role of type 2 cytokines in AD pathophysiology and
+      their contribution to barrier dysfunction, supporting the Th2/type 2
+      immune mechanism.
+  - reference: PMID:21388665
+    supports: PARTIAL
+    evidence_source: HUMAN_CLINICAL
+    snippet: skin lesions contain immune infiltrates of T cells, dendritic
+      cells, and other types of leukocytes. We review similarities between the
+      diseases and differences in epidermal barrier defects and immune cells.
+    explanation: Describes the immune cell infiltrates in AD lesions including T
+      cells and dendritic cells, consistent with type 2 immune response.
+- name: Th17/Th22 Inflammation
+  description: In addition to the dominant Th2 response, Th17 and Th22 cells 
+    contribute to inflammation, particularly in acute lesions and Asian 
+    patients. IL-17 and IL-22 further disrupt epidermal differentiation.
+  biological_processes:
+  - preferred_term: T-helper 17 type immune response
+    term:
+      id: GO:0072538
+      label: T-helper 17 type immune response
+  cell_types:
+  - preferred_term: T-helper 17 cell
+    term:
+      id: CL:0000899
+      label: T-helper 17 cell
+- name: Pruritogen-Induced Neuronal Activation
+  description: IL-31 and other pruritogens activate cutaneous sensory neurons, 
+    generating persistent itch in atopic dermatitis.
+  genes:
+  - preferred_term: IL31
+    term:
+      id: hgnc:19372
+      label: IL31
+  downstream:
+  - target: Scratching-Induced Barrier Injury
+    description: Persistent itch drives repetitive scratching behavior.
+  cell_types:
+  - preferred_term: Sensory neuron
+    term:
+      id: CL:0000101
+      label: sensory neuron
+  evidence:
+  - reference: PMID:30819278
+    supports: PARTIAL
+    evidence_source: HUMAN_CLINICAL
+    snippet: New insights into the pathophysiology of AD have focused on
+      epidermal lipid profiles, neuroimmune interactions, and microbial
+      dysbiosis.
+    explanation: Supports neuroimmune signaling as a component of AD
+      pathophysiology.
+- name: Scratching-Induced Barrier Injury
+  description: Repetitive scratching causes mechanical skin injury and worsens 
+    epidermal barrier dysfunction.
+  downstream:
+  - target: Secondary Inflammatory Amplification
+    description: Mechanical barrier injury increases local inflammatory 
+      activation.
+  cell_types:
+  - preferred_term: Keratinocyte
+    term:
+      id: CL:0000312
+      label: keratinocyte
+- name: Secondary Inflammatory Amplification
+  description: Barrier injury from scratching perpetuates inflammatory signaling
+    and contributes to chronic lesion persistence.
+  biological_processes:
+  - preferred_term: Inflammatory response
+    term:
+      id: GO:0006954
+      label: inflammatory response
+  cell_types:
+  - preferred_term: Keratinocyte
+    term:
+      id: CL:0000312
+      label: keratinocyte
+phenotypes:
+- name: Eczematoid Dermatitis
+  category: Dermatological
+  frequency: VERY_FREQUENT
+  diagnostic: true
+  notes: Erythematous, pruritic patches and plaques with scaling, often in 
+    flexural areas.
+  phenotype_term:
+    preferred_term: Eczematoid dermatitis
+    term:
+      id: HP:0000964
+      label: Eczematoid dermatitis
+- name: Pruritus
+  category: Dermatological
+  frequency: VERY_FREQUENT
+  diagnostic: true
+  notes: Intense itching is the hallmark symptom, often worse at night.
+  phenotype_term:
+    preferred_term: Pruritus
+    term:
+      id: HP:0000989
+      label: Pruritus
+- name: Xerosis
+  category: Dermatological
+  frequency: VERY_FREQUENT
+  notes: Generalized dry skin reflecting barrier dysfunction.
+  phenotype_term:
+    preferred_term: Xerosis
+    term:
+      id: HP:0000958
+      label: Dry skin
+- name: Lichenification
+  category: Dermatological
+  frequency: FREQUENT
+  notes: Thickened, leathery skin from chronic scratching.
+  phenotype_term:
+    preferred_term: Lichenification
+    term:
+      id: HP:0100725
+      label: Lichenification
+- name: Elevated Serum IgE
+  category: Immunological
+  frequency: FREQUENT
+  notes: Present in extrinsic subtype (~80% of patients).
+  phenotype_term:
+    preferred_term: Elevated serum IgE
+    term:
+      id: HP:0003212
+      label: Increased circulating IgE concentration
+genetic:
+- name: FLG
+  association: Associated
+  notes: Loss-of-function variants are the strongest genetic risk factor. R501X 
+    and 2282del4 are common in European populations.
+  evidence:
+  - reference: PMID:16550169
+    supports: SUPPORT
+    evidence_source: HUMAN_CLINICAL
+    snippet: two independent loss-of-function genetic variants (R510X
+      [sic, correct designation is R501X] and 2282del4) in the gene encoding
+      filaggrin (FLG) are very strong predisposing factors for atopic
+      dermatitis. These variants are carried by approximately 9% of people of
+      European origin.
+    explanation: Landmark Palmer et al. 2006 study establishing FLG
+      loss-of-function as the major genetic predisposing factor for atopic
+      dermatitis.
+- name: IL4R
+  association: Associated
+  notes: Variants in IL-4 receptor alpha chain affect Th2 signaling intensity.
+- name: IL13
+  association: Associated
+  notes: Variants affecting IL-13 expression or function.
+- name: STAT6
+  association: Associated
+  notes: Transcription factor downstream of IL-4/IL-13 signaling.
+- name: EMSY
+  association: Associated
+  notes: Chromatin remodeling factor identified in GWAS.
+- name: BACH2
+  association: GWAS
+  notes: Transcription factor regulating Treg/effector T cell balance and B cell
+    class switching
+- name: TNFAIP3
+  association: GWAS
+  notes: Encodes A20, a ubiquitin-editing enzyme that negatively regulates NF-kB
+    signaling
+- name: EGR2
+  association: GWAS
+  notes: Transcription factor involved in T cell anergy and peripheral tolerance
+- name: ETS1
+  association: GWAS
+  notes: Transcription factor regulating T and B cell development and immune 
+    cell differentiation
+- name: IRF4
+  association: GWAS
+  notes: Transcription factor essential for Th17 and Th2 cell differentiation 
+    and plasma cell development
+- name: SATB1
+  association: GWAS
+  notes: Chromatin organizer regulating T cell development and lineage 
+    commitment
+- name: SMAD3
+  association: GWAS
+  notes: TGF-beta signaling mediator regulating T cell differentiation and 
+    immune tolerance
+- name: REL
+  association: GWAS
+  notes: NF-kB subunit c-Rel controlling lymphocyte activation and survival
+environmental:
+- name: Allergen Exposure
+  description: House dust mites, pet dander, and pollens can trigger or 
+    exacerbate disease.
+  effect: TRIGGERS
+- name: Skin Irritants
+  description: Soaps, detergents, and harsh fabrics disrupt the already 
+    compromised barrier.
+  effect: TRIGGERS
+- name: Microbial Dysbiosis
+  description: Staphylococcus aureus colonization is found in >90% of lesional 
+    skin and amplifies inflammation through superantigens and biofilm formation.
+  effect: WORSENS
+treatments:
+- name: Emollients and Moisturizers
+  description: First-line treatment to restore skin barrier function and reduce 
+    transepidermal water loss.
+- name: Topical Corticosteroids
+  description: First-line anti-inflammatory treatment for flares, applied to 
+    affected areas.
+- name: Dupilumab
+  description: Monoclonal antibody targeting IL-4 receptor alpha, blocking both 
+    IL-4 and IL-13 signaling. FDA-approved for moderate-to-severe atopic 
+    dermatitis.
+  treatment_term:
+    preferred_term: pharmacotherapy
+    term:
+      id: MAXO:0000058
+      label: pharmacotherapy
+- name: JAK Inhibitors
+  description: Oral (baricitinib, upadacitinib, abrocitinib) and topical 
+    (ruxolitinib) JAK inhibitors targeting the JAK-STAT pathway downstream of 
+    type 2 cytokines.
+  treatment_term:
+    preferred_term: pharmacotherapy
+    term:
+      id: MAXO:0000058
+      label: pharmacotherapy
+- name: Phototherapy
+  description: Narrowband UVB phototherapy for moderate-to-severe disease.
+disease_term:
+  preferred_term: atopic dermatitis
+  term:
+    id: MONDO:0004980
+    label: atopic eczema
+references:
+- reference: DOI:10.1007/s13555-025-01352-y
+  title: 'Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review'
+  findings: []
+- reference: DOI:10.1038/s41467-023-41857-8
+  title: Multifaceted analysis of cross-tissue transcriptomes reveals 
+    phenotype–endotype associations in atopic dermatitis
+  findings: []
+- reference: DOI:10.1126/sciimmunol.abi6887
+  title: IL-31–dependent neurogenic inflammation restrains cutaneous type 2 
+    immune response in allergic dermatitis
+  findings: []
+- reference: DOI:10.1186/s43556-025-00313-3
+  title: 'Atopic dermatitis: diagnosis, molecular pathogenesis, and therapeutics'
+  findings: []
+- reference: DOI:10.14789/ejmj.jmj24-0036-r
+  title: Mechanisms of Itch in Atopic Dermatitis
+  findings: []
+- reference: DOI:10.3390/jcm12041538
+  title: 'The Role of Tight Junctions in Atopic Dermatitis: A Systematic Review'
+  findings: []
+- reference: DOI:10.3390/jcm14145053
+  title: 'Anti-Inflammatory Therapies for Atopic Dermatitis: A New Era in Targeted
+    Treatment'
+  findings: []
+- reference: DOI:10.64898/2026.01.10.26343854
+  title: 'Protective and Susceptibility Clusters of Environmental Factors, Gene Expression,
+    Antibody Responses, and Cytokines in Pediatric Atopic Dermatitis: Insights from
+    Multi-Modal Data Integration'
+  findings: []
+- reference: DOI:10.7759/cureus.86937
+  title: 'Skin Barrier Dysfunction in Chronic Dermatoses: From Pathophysiology to
+    Emerging Therapeutic Strategies'
+  findings: []