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Immune dysregulation, autoimmunity, and autoinflammation(IDAA)

MedGen UID:
1051793
•Concept ID:
CN375536
•
Disease or Syndrome
Synonyms: ACTIVATING PLCG1 VARIANT-ASSOCIATED SYNDROME; IDAA
 
Gene (location): PLCG1 (20q12)
 
Monarch Initiative: MONDO:0957790
OMIM®: 620514

Definition

Immune dysregulation, autoimmunity, and autoinflammation (IDAA) is an immunologic disorder characterized by anemia and thrombocytopenia associated with circulating autoantibodies, positive Coombs test, and increased levels of proinflammatory cytokines due to constitutive activation of immune-related signaling pathways (Tao et al., 2023). [from OMIM]

Professional guidelines

PubMed

Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.
Lorenzini T, Fliegauf M, Klammer N, Frede N, Proietti M, Bulashevska A, Camacho-Ordonez N, Varjosalo M, Kinnunen M, de Vries E, van der Meer JWM, Ameratunga R, Roifman CM, Schejter YD, Kobbe R, Hautala T, Atschekzei F, Schmidt RE, Schröder C, Stepensky P, Shadur B, Pedroza LA, van der Flier M, Martínez-Gallo M, Gonzalez-Granado LI, Allende LM, Shcherbina A, Kuzmenko N, Zakharova V, Neves JF, Svec P, Fischer U, Ip W, Bartsch O, Barış S, Klein C, Geha R, Chou J, Alosaimi M, Weintraub L, Boztug K, Hirschmugl T, Dos Santos Vilela MM, Holzinger D, Seidl M, Lougaris V, Plebani A, Alsina L, Piquer-Gibert M, Deyà-Martínez A, Slade CA, Aghamohammadi A, Abolhassani H, Hammarström L, Kuismin O, Helminen M, Allen HL, Thaventhiran JE, Freeman AF, Cook M, Bakhtiar S, Christiansen M, Cunningham-Rundles C, Patel NC, Rae W, Niehues T, Brauer N, Syrjänen J, Seppänen MRJ, Burns SO, Tuijnenburg P, Kuijpers TW; NIHR BioResource, Warnatz K, Grimbacher B; NIHR BioResource
J Allergy Clin Immunol 2020 Oct;146(4):901-911. Epub 2020 Apr 9 doi: 10.1016/j.jaci.2019.11.051. PMID: 32278790Free PMC Article
Hereditary Autoinflammatory Disorders: Recognition and Treatment.
Broderick L
Immunol Allergy Clin North Am 2019 Feb;39(1):13-29. Epub 2018 Nov 1 doi: 10.1016/j.iac.2018.08.004. PMID: 30466770

Recent clinical studies

Etiology

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Baysac K, Sun G, Nakano H, Schmitz EG, Cruz AC, Fisher C, Bailey AC; PLCG2-Immune Dysregulation Working Group, Mace E, Milner JD, Ombrello MJ
J Allergy Clin Immunol 2024 Jan;153(1):230-242. Epub 2023 Sep 26 doi: 10.1016/j.jaci.2023.08.036. PMID: 37769878
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Autoinflammatory syndromes.
Meier-Schiesser B, French LE
J Dtsch Dermatol Ges 2021 Mar;19(3):400-426. Epub 2021 Feb 23 doi: 10.1111/ddg.14332. PMID: 33620111
Immunodeficiencies: non-infectious manifestations.
Goudouris ES
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S24-S33. Epub 2020 Nov 8 doi: 10.1016/j.jped.2020.10.004. PMID: 33176164Free PMC Article
Autoimmunity, Autoinflammation, and Infection in Uveitis.
Forrester JV, Kuffova L, Dick AD
Am J Ophthalmol 2018 May;189:77-85. Epub 2018 Mar 2 doi: 10.1016/j.ajo.2018.02.019. PMID: 29505775

Diagnosis

Approach to Diagnosing Inborn Errors of Immunity.
Peng X, Kaviany S
Rheum Dis Clin North Am 2023 Nov;49(4):731-739. Epub 2023 Jul 21 doi: 10.1016/j.rdc.2023.06.001. PMID: 37821192
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Autoinflammatory syndromes.
Meier-Schiesser B, French LE
J Dtsch Dermatol Ges 2021 Mar;19(3):400-426. Epub 2021 Feb 23 doi: 10.1111/ddg.14332. PMID: 33620111
Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification.
Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Torgerson TR, Casanova JL, Sullivan KE, Tangye SG
J Clin Immunol 2020 Jan;40(1):66-81. Epub 2020 Feb 11 doi: 10.1007/s10875-020-00758-x. PMID: 32048120Free PMC Article
Hereditary Autoinflammatory Disorders: Recognition and Treatment.
Broderick L
Immunol Allergy Clin North Am 2019 Feb;39(1):13-29. Epub 2018 Nov 1 doi: 10.1016/j.iac.2018.08.004. PMID: 30466770

Therapy

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect.
He T, Xia Y, Yang J
Pediatr Rheumatol Online J 2021 Jan 22;19(1):9. doi: 10.1186/s12969-021-00497-2. PMID: 33482855Free PMC Article
The role of the inflammasome in patients with autoinflammatory diseases.
Hoffman HM, Broderick L
J Allergy Clin Immunol 2016 Jul;138(1):3-14. Epub 2016 May 17 doi: 10.1016/j.jaci.2016.05.001. PMID: 27373321
Regulating against the dysregulation: new treatment options in autoinflammation.
Kallinich T
Semin Immunopathol 2015 Jul;37(4):429-37. Epub 2015 Jun 10 doi: 10.1007/s00281-015-0501-9. PMID: 26059720

Prognosis

Trained Immunity Contribution to Autoimmune and Inflammatory Disorders.
Funes SC, Rios M, Fernández-Fierro A, Di Genaro MS, Kalergis AM
Front Immunol 2022;13:868343. Epub 2022 Apr 8 doi: 10.3389/fimmu.2022.868343. PMID: 35464438Free PMC Article
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Lymphadenopathy at the crossroad between immunodeficiency and autoinflammation: An intriguing challenge.
Costagliola G, Consolini R
Clin Exp Immunol 2021 Sep;205(3):288-305. Epub 2021 Jun 20 doi: 10.1111/cei.13620. PMID: 34008169Free PMC Article
Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.
Lorenzini T, Fliegauf M, Klammer N, Frede N, Proietti M, Bulashevska A, Camacho-Ordonez N, Varjosalo M, Kinnunen M, de Vries E, van der Meer JWM, Ameratunga R, Roifman CM, Schejter YD, Kobbe R, Hautala T, Atschekzei F, Schmidt RE, Schröder C, Stepensky P, Shadur B, Pedroza LA, van der Flier M, Martínez-Gallo M, Gonzalez-Granado LI, Allende LM, Shcherbina A, Kuzmenko N, Zakharova V, Neves JF, Svec P, Fischer U, Ip W, Bartsch O, Barış S, Klein C, Geha R, Chou J, Alosaimi M, Weintraub L, Boztug K, Hirschmugl T, Dos Santos Vilela MM, Holzinger D, Seidl M, Lougaris V, Plebani A, Alsina L, Piquer-Gibert M, Deyà-Martínez A, Slade CA, Aghamohammadi A, Abolhassani H, Hammarström L, Kuismin O, Helminen M, Allen HL, Thaventhiran JE, Freeman AF, Cook M, Bakhtiar S, Christiansen M, Cunningham-Rundles C, Patel NC, Rae W, Niehues T, Brauer N, Syrjänen J, Seppänen MRJ, Burns SO, Tuijnenburg P, Kuijpers TW; NIHR BioResource, Warnatz K, Grimbacher B; NIHR BioResource
J Allergy Clin Immunol 2020 Oct;146(4):901-911. Epub 2020 Apr 9 doi: 10.1016/j.jaci.2019.11.051. PMID: 32278790Free PMC Article
Dysregulation of Cell Death in Human Chronic Inflammation.
Li Y, Klein C, Kotlarz D
Cold Spring Harb Perspect Biol 2020 Jul 1;12(7) doi: 10.1101/cshperspect.a037036. PMID: 31843991Free PMC Article

Clinical prediction guides

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Baysac K, Sun G, Nakano H, Schmitz EG, Cruz AC, Fisher C, Bailey AC; PLCG2-Immune Dysregulation Working Group, Mace E, Milner JD, Ombrello MJ
J Allergy Clin Immunol 2024 Jan;153(1):230-242. Epub 2023 Sep 26 doi: 10.1016/j.jaci.2023.08.036. PMID: 37769878
HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions.
Cook S, Lenardo MJ, Freeman AF
J Clin Immunol 2022 Nov;42(8):1583-1592. Epub 2022 Jul 22 doi: 10.1007/s10875-022-01327-0. PMID: 35869404Free PMC Article
Pediatric recurrent fever and autoinflammation from the perspective of an allergist/immunologist.
Broderick L, Hoffman HM
J Allergy Clin Immunol 2020 Nov;146(5):960-966.e2. Epub 2020 Sep 28 doi: 10.1016/j.jaci.2020.09.019. PMID: 33002514Free PMC Article
Down Syndrome and COVID-19: A Perfect Storm?
Espinosa JM
Cell Rep Med 2020 May 19;1(2):100019. Epub 2020 May 1 doi: 10.1016/j.xcrm.2020.100019. PMID: 32501455Free PMC Article
Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.
Lorenzini T, Fliegauf M, Klammer N, Frede N, Proietti M, Bulashevska A, Camacho-Ordonez N, Varjosalo M, Kinnunen M, de Vries E, van der Meer JWM, Ameratunga R, Roifman CM, Schejter YD, Kobbe R, Hautala T, Atschekzei F, Schmidt RE, Schröder C, Stepensky P, Shadur B, Pedroza LA, van der Flier M, Martínez-Gallo M, Gonzalez-Granado LI, Allende LM, Shcherbina A, Kuzmenko N, Zakharova V, Neves JF, Svec P, Fischer U, Ip W, Bartsch O, Barış S, Klein C, Geha R, Chou J, Alosaimi M, Weintraub L, Boztug K, Hirschmugl T, Dos Santos Vilela MM, Holzinger D, Seidl M, Lougaris V, Plebani A, Alsina L, Piquer-Gibert M, Deyà-Martínez A, Slade CA, Aghamohammadi A, Abolhassani H, Hammarström L, Kuismin O, Helminen M, Allen HL, Thaventhiran JE, Freeman AF, Cook M, Bakhtiar S, Christiansen M, Cunningham-Rundles C, Patel NC, Rae W, Niehues T, Brauer N, Syrjänen J, Seppänen MRJ, Burns SO, Tuijnenburg P, Kuijpers TW; NIHR BioResource, Warnatz K, Grimbacher B; NIHR BioResource
J Allergy Clin Immunol 2020 Oct;146(4):901-911. Epub 2020 Apr 9 doi: 10.1016/j.jaci.2019.11.051. PMID: 32278790Free PMC Article

Recent systematic reviews

Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article

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      Related medical variations
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      Related information in NCBI Gene
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