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Autoimmune interstitial lung disease-arthritis syndrome(AILJK)

MedGen UID:
1800821
Concept ID:
C5243948
Disease or Syndrome
Synonyms: Autoimmune interstitial lung, joint, and kidney disease; AUTOINFLAMMATION AND AUTOIMMUNITY, SYSTEMIC, WITH IMMUNE DYSREGULATION
SNOMED CT: COPA (coatomer protein complex subunit alpha) syndrome (1222679006); Autoimmune interstitial lung disease, arthritis syndrome (1222679006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): COPA (1q23.2)
 
Monarch Initiative: MONDO:0014629
OMIM®: 616414
Orphanet: ORPHA444092

Definition

Systemic autoinflammation and autoimmunity with immune dysregulation (AIAISD) is an autosomal dominant systemic autoinflammatory disorder with autoimmunity and immune dysregulation. Affected individuals present in the first decade of life with variable features that may include interstitial lung disease, alveolar hemorrhage, inflammatory arthritis, neuromyelitis optica, livedo reticularis, dysautonomia, recurrent infections, and renal disease. Laboratory studies usually show high-titer autoantibodies and features of inflammation, including a type I interferon (e.g., 147660) signature and elevation of inflammatory cytokines. The disorder shows significant incomplete penetrance; most carrier parents are unaffected (summary by Watkin et al., 2015; Delafontaine et al., 2024). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Mesangial hypercellularity
MedGen UID:
924090
Concept ID:
C4281741
Cell or Molecular Dysfunction
Increased numbers of mesangial cells per glomerulus, defined as more than 3 nuclei fully surrounded by matrix in one or more mesangial areas, not including perihilar region, on a standard 3-micron-thick tissue section, best evaluated on periodic acid-Schiff (PAS) stain.
Pulmonary hemorrhage
MedGen UID:
57732
Concept ID:
C0151701
Pathologic Function
Pulmonary hemorrhage is a bleeding within the lungs. Older children and adults may spit blood or bloody sputum. Neonates, infants and young children usually do not spit up blood. Anemia, pulmonary infiltrates, increasingling bloody return on BAL and the presence of hemosiderin-laden macrophages in broncho-alveolar lavage (BAL) fluid or lung biopsy can diagnose lung bleeding. Alveolar macrophages contain phagocytosed red blood cells and stain positive for hemosiderin, a product of hemoglobin degradation, after about 48-72 hours following pulmonary hemorraghe. Previous or recurrent bleeding can thus be distinguished from fresh events. A differentiation into local or diffuse is of importance. Also differentiate if pulmonary hemorrhage is due to a primary lung disorder or a manifestation of a systemic disease.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Hemosiderin-laden macrophages in bronchoalveolar fluid
MedGen UID:
1717924
Concept ID:
C5397971
Finding
Hemosiderin-laden macrophages (HLM) in bronchoalveolar lavage (BAL) fluid were originally known as adiagnostic biomarker of alveolar hemorrhage, but have also been observed in idiopathic pulmonary fibrosis (IPF) with histopathological pattern of usual interstitial pneumonia (UIP).
Abnormal pulmonary interstitial morphology
MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Crescentic glomerulonephritis
MedGen UID:
96040
Concept ID:
C0403416
Disease or Syndrome
A type of extracapillary glomerulonephritis characterized by the formation of crescent-like cellular proliferation.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutoimmune interstitial lung disease-arthritis syndrome

Recent clinical studies

Etiology

Infantino M, Palterer B, Biagiotti R, Almerigogna F, Benucci M, Damiani A, Grossi V, Azzurri A, Casprini P, Bacci G, Giudizi MG, Manfredi M
Immunol Res 2018 Feb;66(1):74-78. doi: 10.1007/s12026-017-8974-3. PMID: 29159696

Diagnosis

Infantino M, Palterer B, Biagiotti R, Almerigogna F, Benucci M, Damiani A, Grossi V, Azzurri A, Casprini P, Bacci G, Giudizi MG, Manfredi M
Immunol Res 2018 Feb;66(1):74-78. doi: 10.1007/s12026-017-8974-3. PMID: 29159696
Hirakata M
Nihon Rinsho Meneki Gakkai Kaishi 2007 Dec;30(6):444-54. doi: 10.2177/jsci.30.444. PMID: 18174673

Prognosis

Kowitz M, Chakradeo K, Hennessey A, Wolski P
BMJ Case Rep 2021 May 11;14(5) doi: 10.1136/bcr-2020-240929. PMID: 33975837Free PMC Article
Hirakata M
Nihon Rinsho Meneki Gakkai Kaishi 2007 Dec;30(6):444-54. doi: 10.2177/jsci.30.444. PMID: 18174673

Clinical prediction guides

Infantino M, Palterer B, Biagiotti R, Almerigogna F, Benucci M, Damiani A, Grossi V, Azzurri A, Casprini P, Bacci G, Giudizi MG, Manfredi M
Immunol Res 2018 Feb;66(1):74-78. doi: 10.1007/s12026-017-8974-3. PMID: 29159696
Hirakata M
Nihon Rinsho Meneki Gakkai Kaishi 2007 Dec;30(6):444-54. doi: 10.2177/jsci.30.444. PMID: 18174673