Autoinflammatory Disorder IEIs (IUIS Table 7)

name: Autoinflammatory Disorder IEIs
display_name: Autoinflammatory Disorder IEIs (IUIS Table 7)
creation_date: "2026-08-20T00:00:00Z"
description: >-
  IUIS Table 7 — autoinflammatory disorders. These inborn errors of immunity
  drive sterile, antigen-independent inflammation through unrestrained innate
  signalling — inflammasome activation and IL-1beta release, constitutive type I
  interferon production, or dysregulated NF-kappaB — rather than through
  autoantibodies or autoreactive lymphocytes. The clinical signature is
  recurrent or continuous fever, rash, serositis and arthropathy with a raised
  acute-phase response and no identifiable infection or high-titre
  autoantibody.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the IUIS Table 7 pattern of monogenic sterile innate inflammation.
  Members are kept as separate Disease entries because the deregulated innate
  circuit differs, and that difference is what determines treatment: CINCA is
  inflammasome/IL-1beta-driven and answers to IL-1 blockade, whereas COPA
  syndrome is a type I interferonopathy driven by failed STING retrieval and
  does not. Grouping them keeps the inflammasome and interferon arms of
  autoinflammation visible as siblings rather than collapsing them into a
  single "periodic fever" bucket.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0019751
      label: autoinflammatory syndrome
    mapping_predicate: skos:broadMatch
    mapping_source: MONDO
    mapping_justification: >-
      IUIS Table 7 aligns with MONDO autoinflammatory syndrome
      (MONDO:0019751), but broadMatch rather than exactMatch: MONDO's class is
      phenotype-defined and admits non-monogenic and acquired autoinflammatory
      disease, whereas IUIS Table 7 is restricted to germline monogenic inborn
      errors. The MONDO term is therefore strictly wider than this grouping.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        Both listed members are is-a descendants of MONDO:0019751, verified
        2026-08-20 with `runoak -i sqlite:obo:mondo descendants -p i
        MONDO:0019751` (CINCA syndrome MONDO:0011776; COPA syndrome is carried
        by MONDO as autoimmune interstitial lung disease-arthritis syndrome,
        MONDO:0014629).
membership_criteria:
- description: >-
    A disorder belongs to IUIS Table 7 if it is a germline monogenic inborn
    error of immunity causing sterile, antigen-independent innate inflammation
    — via inflammasome/IL-1, type I interferon, or NF-kappaB dysregulation —
    rather than antibody- or lymphocyte-mediated autoimmunity.
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_CLASSIFICATION
    classification: "iuis_category:autoinflammatory syndrome"
    description: >-
      Assigned to IUIS Table 7 (autoinflammatory disorders) via
      classifications.iuis_category on the member Disease entry. Stated in the
      keyed `<slot>:<value>` form so the audit reads the structured
      classifications block.
members:
- member: CINCA Syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Gain-of-function NLRP3 drives constitutive inflammasome assembly and
      excessive IL-1beta release — the inflammasome arm of Table 7, and its
      severe end: CINCA/NOMID is the most severe cryopyrin-associated periodic
      syndrome phenotype, with neonatal urticarial rash, chronic aseptic
      meningitis, sensorineural hearing loss and epiphyseal overgrowth.
    gene:
      preferred_term: NLRP3
      term:
        id: hgnc:16400
        label: NLRP3
- member: COPA Syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Heterozygous COPA variants impair COPI-mediated retrograde Golgi-to-ER
      trafficking, so the SURF4 adapter fails to retrieve STING; STING
      accumulates and signals ligand-independently. The type I interferonopathy
      arm of Table 7, and the member that reaches autoinflammation through a
      housekeeping vesicular-transport defect rather than an immune sensor,
      presenting as interstitial lung disease with arthritis and
      autoantibodies.
    gene:
      preferred_term: COPA
      term:
        id: hgnc:2230
        label: COPA
notes: >-
  Created 2026-08-20 to give the IUIS Table 7 disorders a place in the Inborn
  Errors of Immunity tree; both members already carried
  `classifications.iuis_category: autoinflammatory syndrome` but were
  unreachable from the umbrella grouping. Aicardi-Goutieres Syndrome, Familial
  Cold Autoinflammatory Syndrome and Proteasome-Associated Autoinflammatory
  Syndrome are curated in kb/disorders/ and are strong Table 7 candidates, but
  carry no iuis_category assignment yet — tracked in the
  `iuis_category_backfill_candidates` discussion on the umbrella Inborn Errors
  of Immunity grouping.