APLAID
MCID: ATN022
MIFTS: 30

Autoinflammation, Antibody Deficiency, and Immune Dysregulation (APLAID)

Categories: Bone diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

MalaCards integrated aliases for Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

Name: Autoinflammation, Antibody Deficiency, and Immune Dysregulation 56
Autoinflammation, Antibody Deficiency, and Immune Dysregulation, Plcg2-Associated 56 29 6 39
Aplaid 56 58 73
Autoinflammation, Antibody Deficiency, and Immune Dysregulation Syndrome 56 13
Autoinflammation and Plcg2-Associated Antibody Deficiency and Immune Dysregulation 36
Autoinflammation, Antibody Deficiency, and Immune Dysregulation Plcg2-Associated 73
Autoinflammation-Plcg2-Associated Antibody Deficiency-Immune Dysregulation 58

Characteristics:

Orphanet epidemiological data:

58
autoinflammation-plcg2-associated antibody deficiency-immune dysregulation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy
one family has been reported (last curated october 2012)
skin lesions worsen with heat or sun exposure


HPO:

31
autoinflammation, antibody deficiency, and immune dysregulation:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare systemic and rhumatological diseases


Summaries for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

KEGG : 36 Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) is a rare autosomal dominant autoinflammatory disease caracterized by early-onset recurrent erythematous plaques and vesiculopustular skin lesions associated with arthralgia, corneal erosions, and interstitial pneumonia. APLAID is an allelic disorder of PLCG2-associated antibody deficiency and immune dysregulation (PLAID) with some overlapping features. A recent study demonstrated that a family with an autoinflammatory disease was found to have point mutations in the same CSH2 domain of PLCG2. The patients identified with APLAID developed recurrent sinopulmonary infections presumably due to a lack of class-switched memory B cells on lymphocyte immunophenotyping. The patients were partially responsive to anakinra and to high-dose corticosteroids.

MalaCards based summary : Autoinflammation, Antibody Deficiency, and Immune Dysregulation, also known as autoinflammation, antibody deficiency, and immune dysregulation, plcg2-associated, is related to exanthem and familial mediterranean fever, and has symptoms including arthralgia An important gene associated with Autoinflammation, Antibody Deficiency, and Immune Dysregulation is PLCG2 (Phospholipase C Gamma 2), and among its related pathways/superpathways is NF-kappa B signaling pathway. Affiliated tissues include skin, eye and b cells, and related phenotypes are cataract and corneal erosion

OMIM : 56 Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) is an autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies (summary by Zhou et al., 2012). (614878)

UniProtKB/Swiss-Prot : 73 Autoinflammation, antibody deficiency, and immune dysregulation PLCG2-associated: An autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies.

Related Diseases for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Diseases related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 exanthem 10.3
2 familial mediterranean fever 10.1
3 branchiootic syndrome 1 10.1
4 familial cold autoinflammatory syndrome 3 10.1
5 brucellosis 10.1
6 posterior uveitis 10.1
7 uveitis 10.1
8 urticaria 10.1
9 cutis laxa 10.1

Graphical network of the top 20 diseases related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:



Diseases related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Symptoms & Phenotypes for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Human phenotypes related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 cataract 31 occasional (7.5%) HP:0000518
2 corneal erosion 31 occasional (7.5%) HP:0200020
3 ulcerative colitis 31 occasional (7.5%) HP:0100279
4 arthralgia 31 HP:0002829
5 erythema 31 HP:0010783
6 cellulitis 31 HP:0100658
7 decreased circulating iga level 31 HP:0002720
8 decreased circulating total igm 31 HP:0002850
9 interstitial pneumonitis 31 HP:0006515
10 immune dysregulation 31 HP:0002958
11 bronchiolitis 31 HP:0011950

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
cellulitis
blistering skin lesions, recurrent
erythematous plaques
vesiculopustular lesions

Skeletal:
arthralgias

Head And Neck Eyes:
cataracts (1 patient)
eye inflammation (1 patient)
corneal blisters (1 patient)
corneal erosions (1 patient)

Abdomen Gastrointestinal:
ulcerative colitis (1 patient)

Respiratory Lung:
interstitial pneumonitis
respiratory bronchiolitis

Immunology:
decreased igm
decreased iga
impaired b cell memory cells
lack of autoantibodies
decreased numbers of nk t cells

Respiratory:
sinopulmonary infections, recurrent

Skin Nails Hair Skin Histology:
inflammatory infiltrate of neutrophils, lymphocytes, eosinophils, and histiocytes

Clinical features from OMIM:

614878

UMLS symptoms related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:


arthralgia

Drugs & Therapeutics for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Search Clinical Trials , NIH Clinical Center for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Genetic Tests for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Genetic tests related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

# Genetic test Affiliating Genes
1 Autoinflammation, Antibody Deficiency, and Immune Dysregulation, Plcg2-Associated 29 PLCG2

Anatomical Context for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

MalaCards organs/tissues related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

40
Skin, Eye, B Cells, Bone, T Cells, Neutrophil

Publications for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Articles related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

# Title Authors PMID Year
1
Novel PLCG2 Mutation in a Patient With APLAID and Cutis Laxa. 61 6 56
30619256 2018
2
A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. 6 56
23000145 2012
3
Characterization of phospholipase C gamma enzymes with gain-of-function mutations. 56
19531496 2009
4
Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry. 56
15845450 2005
5
A new report of autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) with a homozygous pattern from Iran. 61
32014489 2020
6
A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases. 61
31853824 2020
7
Expanding the clinical features of autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation by description of a novel patient. 61
31465591 2019
8
Functional characterization of phospholipase C-γ2 mutant protein causing both somatic ibrutinib resistance and a germline monogenic autoinflammatory disorder. 61
30344948 2018
9
Connecting two pathways through Ca 2+ signaling: NLRP3 inflammasome activation induced by a hypermorphic PLCG2 mutation. 61
25418813 2015

Variations for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

ClinVar genetic disease variations for Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLCG2 NM_002661.5(PLCG2):c.2120C>A (p.Ser707Tyr)SNV Pathogenic 39696 rs397514562 16:81953154-81953154 16:81919549-81919549
2 PLCG2 NM_002661.5(PLCG2):c.923C>T (p.Ala308Val)SNV Conflicting interpretations of pathogenicity 472906 rs199636472 16:81925132-81925132 16:81891527-81891527
3 PLCG2 NM_002661.5(PLCG2):c.77C>T (p.Thr26Met)SNV Conflicting interpretations of pathogenicity 618829 rs189301790 16:81819671-81819671 16:81786066-81786066
4 PLCG2 NM_002661.5(PLCG2):c.2031C>T (p.Ser677=)SNV Conflicting interpretations of pathogenicity 626149 rs759929786 16:81946298-81946298 16:81912693-81912693
5 PLCG2 NM_002661.5(PLCG2):c.304A>G (p.Thr102Ala)SNV Uncertain significance 827987 16:81888159-81888159 16:81854554-81854554
6 PLCG2 NM_002661.5(PLCG2):c.2542C>T (p.Leu848Phe)SNV Benign/Likely benign 445522 rs114618894 16:81962190-81962190 16:81928585-81928585

UniProtKB/Swiss-Prot genetic disease variations for Autoinflammation, Antibody Deficiency, and Immune Dysregulation:

73
# Symbol AA change Variation ID SNP ID
1 PLCG2 p.Ser707Tyr VAR_069211 rs397514562

Expression for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Search GEO for disease gene expression data for Autoinflammation, Antibody Deficiency, and Immune Dysregulation.

Pathways for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Pathways related to Autoinflammation, Antibody Deficiency, and Immune Dysregulation according to KEGG:

36
# Name Kegg Source Accession
1 NF-kappa B signaling pathway hsa04064

GO Terms for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

Sources for Autoinflammation, Antibody Deficiency, and Immune Dysregulation

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....