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Immune dysregulation

MedGen UID:
335001
Concept ID:
C1844666
Finding
Synonym: Unregulated immune response
 
HPO: HP:0002958

Definition

Altered immune function characterized by lymphoid proliferation, immune activation, and excessive autoreactivity often leading to autoimmune/inflammatory complications. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImmune dysregulation

Conditions with this feature

Insulin-dependent diabetes mellitus secretory diarrhea syndrome
MedGen UID:
83339
Concept ID:
C0342288
Disease or Syndrome
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, endocrinopathy (most commonly insulin-dependent diabetes mellitus), and eczematous dermatitis. Most children have other autoimmune phenomena including cytopenias, autoimmune hepatitis, or nephropathy; lymphadenopathy, splenomegaly, alopecia, arthritis, and lung disease related to immune dysregulation have all been observed. Fetal presentation of IPEX includes hydrops, echogenic bowel, skin desquamation, IUGR, and fetal akinesia. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements, severe malabsorption, or sepsis; a few with a milder phenotype have survived into the second or third decade of life.
Spondyloenchondrodysplasia with immune dysregulation
MedGen UID:
375009
Concept ID:
C1842763
Disease or Syndrome
Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an immunoosseous dysplasia combining the typical metaphyseal and vertebral bone lesions of spondyloenchondrodysplasia (SPENCD) with immune dysfunction and neurologic involvement. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present (Menger et al., 1989). Central nervous system involvement includes spasticity, mental retardation, and cerebral calcifications, and immune dysregulation ranges from autoimmunity to immunodeficiency. Neurologic and autoimmune manifestations have been observed in different combinations within a single family, suggesting that this disorder may be defined by specific radiographic features but has remarkably pleiotropic manifestations (Renella et al., 2006). Briggs et al. (2016) also noted variability in skeletal, neurologic, and immune phenotypes, which was sometimes marked between members of the same family. Classification of the Enchondromatoses In their classification of the enchondromatoses, Spranger et al. (1978) called Ollier disease and Maffucci syndrome types I and II enchondromatosis, respectively; metachondromatosis (156250), type III; and spondyloenchondrodysplasia (SPENCD), also called spondyloenchondromatosis, type IV; enchondromatosis with irregular vertebral lesions, type V; and generalized enchondromatosis, type VI. Halal and Azouz (1991) added 3 tentative categories to the 6 in the classification of Spranger et al. (1978). Pansuriya et al. (2010) suggested a new classification of enchondromatosis (multiple enchondromas).
Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
MedGen UID:
481620
Concept ID:
C3279990
Disease or Syndrome
IMD31C is a disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1 (600555). Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis (CMC). Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation (summary by Uzel et al., 2013 and Sampaio et al., 2013).
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation
MedGen UID:
766875
Concept ID:
C3553961
Disease or Syndrome
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).
Obesity due to leptin receptor gene deficiency
MedGen UID:
767139
Concept ID:
C3554225
Disease or Syndrome
Leptin receptor deficiency is characterized by severe early-onset obesity, major hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (summary by Dehghani et al., 2018).
Severe combined immunodeficiency due to LAT deficiency
MedGen UID:
1384124
Concept ID:
C4479588
Disease or Syndrome
IMD52 is an autosomal recessive primary immunodeficiency with variable manifestations, including severe combined immunodeficiency, hematologic autoimmune disorders, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy, and most die without bone marrow transplantation. The variable clinical features result from a defect in T-cell receptor signaling (summary by Keller et al., 2016 and Bacchelli et al., 2017).

Professional guidelines

PubMed

Glass DS, Grossfeld D, Renna HA, Agarwala P, Spiegler P, DeLeon J, Reiss AB
Clin Respir J 2022 Feb;16(2):84-96. Epub 2022 Jan 10 doi: 10.1111/crj.13466. PMID: 35001525Free PMC Article
Frazier W, Bhardwaj N
Am Fam Physician 2020 May 15;101(10):590-598. PMID: 32412211
Grover M, Farrugia G, Stanghellini V
Gut 2019 Dec;68(12):2238-2250. Epub 2019 Sep 28 doi: 10.1136/gutjnl-2019-318712. PMID: 31563877Free PMC Article

Recent clinical studies

Etiology

Lazar S, Kahlenberg JM
Annu Rev Med 2023 Jan 27;74:339-352. Epub 2022 Jul 8 doi: 10.1146/annurev-med-043021-032611. PMID: 35804480
Jiang I, Yong PJ, Allaire C, Bedaiwy MA
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115644. PMID: 34073257Free PMC Article
Yong SJ
Infect Dis (Lond) 2021 Oct;53(10):737-754. Epub 2021 May 22 doi: 10.1080/23744235.2021.1924397. PMID: 34024217Free PMC Article
Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S
J Am Coll Cardiol 2020 Oct 6;76(14):1690-1702. doi: 10.1016/j.jacc.2020.08.014. PMID: 33004135
Noone DG, Iijima K, Parekh R
Lancet 2018 Jul 7;392(10141):61-74. Epub 2018 Jun 14 doi: 10.1016/S0140-6736(18)30536-1. PMID: 29910038

Diagnosis

Lazar S, Kahlenberg JM
Annu Rev Med 2023 Jan 27;74:339-352. Epub 2022 Jul 8 doi: 10.1146/annurev-med-043021-032611. PMID: 35804480
Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppänen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I
J Clin Immunol 2022 Oct;42(7):1473-1507. Epub 2022 Jun 24 doi: 10.1007/s10875-022-01289-3. PMID: 35748970Free PMC Article
Ramírez-Marín HA, Silverberg JI
Pediatr Dermatol 2022 May;39(3):345-353. Epub 2022 Mar 16 doi: 10.1111/pde.14971. PMID: 35297082
Glass DS, Grossfeld D, Renna HA, Agarwala P, Spiegler P, DeLeon J, Reiss AB
Clin Respir J 2022 Feb;16(2):84-96. Epub 2022 Jan 10 doi: 10.1111/crj.13466. PMID: 35001525Free PMC Article
Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S
J Am Coll Cardiol 2020 Oct 6;76(14):1690-1702. doi: 10.1016/j.jacc.2020.08.014. PMID: 33004135

Therapy

Alivernini S, Firestein GS, McInnes IB
Immunity 2022 Dec 13;55(12):2255-2270. doi: 10.1016/j.immuni.2022.11.009. PMID: 36516818
Ballester P, Cerdá B, Arcusa R, Marhuenda J, Yamedjeu K, Zafrilla P
Molecules 2022 Oct 25;27(21) doi: 10.3390/molecules27217223. PMID: 36364048Free PMC Article
Glass DS, Grossfeld D, Renna HA, Agarwala P, Spiegler P, DeLeon J, Reiss AB
Clin Respir J 2022 Feb;16(2):84-96. Epub 2022 Jan 10 doi: 10.1111/crj.13466. PMID: 35001525Free PMC Article
Nakase H, Sato N, Mizuno N, Ikawa Y
Autoimmun Rev 2022 Mar;21(3):103017. Epub 2021 Dec 10 doi: 10.1016/j.autrev.2021.103017. PMID: 34902606
Noone DG, Iijima K, Parekh R
Lancet 2018 Jul 7;392(10141):61-74. Epub 2018 Jun 14 doi: 10.1016/S0140-6736(18)30536-1. PMID: 29910038

Prognosis

Cunningham CA, Coppler PJ, Skolnik AB
Resuscitation 2022 Oct;179:116-123. Epub 2022 Aug 24 doi: 10.1016/j.resuscitation.2022.08.013. PMID: 36028143
Jiang I, Yong PJ, Allaire C, Bedaiwy MA
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115644. PMID: 34073257Free PMC Article
Noone DG, Iijima K, Parekh R
Lancet 2018 Jul 7;392(10141):61-74. Epub 2018 Jun 14 doi: 10.1016/S0140-6736(18)30536-1. PMID: 29910038
Kernan KF, Carcillo JA
Int Immunol 2017 Nov 1;29(9):401-409. doi: 10.1093/intimm/dxx031. PMID: 28541437Free PMC Article
Raje N, Dinakar C
Immunol Allergy Clin North Am 2015 Nov;35(4):599-623. Epub 2015 Aug 25 doi: 10.1016/j.iac.2015.07.001. PMID: 26454309Free PMC Article

Clinical prediction guides

Zoine JT, Moore SE, Velasquez MP
Front Immunol 2022;13:867103. Epub 2022 Mar 25 doi: 10.3389/fimmu.2022.867103. PMID: 35401520Free PMC Article
Jiang I, Yong PJ, Allaire C, Bedaiwy MA
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115644. PMID: 34073257Free PMC Article
Thanou A, Jupe E, Purushothaman M, Niewold TB, Munroe ME
J Autoimmun 2021 May;119:102615. Epub 2021 Feb 22 doi: 10.1016/j.jaut.2021.102615. PMID: 33631651Free PMC Article
Kernan KF, Carcillo JA
Int Immunol 2017 Nov 1;29(9):401-409. doi: 10.1093/intimm/dxx031. PMID: 28541437Free PMC Article
Sarin SK, Choudhury A
Nat Rev Gastroenterol Hepatol 2016 Mar;13(3):131-49. Epub 2016 Feb 3 doi: 10.1038/nrgastro.2015.219. PMID: 26837712

Recent systematic reviews

Khan MB, Yang ZS, Lin CY, Hsu MC, Urbina AN, Assavalapsakul W, Wang WH, Chen YH, Wang SF
J Infect Public Health 2023 Oct;16(10):1625-1642. Epub 2023 Aug 3 doi: 10.1016/j.jiph.2023.08.001. PMID: 37595484
Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG, Pérez-Herrera LC, Chu AWL, Ceccaci R, Acosta-Madiedo AS, Wen A, Moreno-López S, MacDonald M, Barrios M, Chu X, Islam N, Gao Y, Wong MM, Couban R, Garcia E, Chapman E, Oykhman P, Chen L, Winders T, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, Frazier WT, Greenhawt M, Huynh J, Kim E, LeBovidge J, Lind ML, Lio P, Martin SA, O'Brien M, Ong PY, Silverberg JI, Spergel J, Wang J, Wheeler KE, Schneider L, Chu DK
J Allergy Clin Immunol 2023 Jan;151(1):147-158. Epub 2022 Sep 30 doi: 10.1016/j.jaci.2022.09.020. PMID: 36191689
Jiao H, Acar G, Robinson GA, Ciurtin C, Jury EC, Kalea AZ
Int J Environ Res Public Health 2022 Sep 20;19(19) doi: 10.3390/ijerph191911895. PMID: 36231195Free PMC Article
Wang WH, Urbina AN, Chang MR, Assavalapsakul W, Lu PL, Chen YH, Wang SF
J Microbiol Immunol Infect 2020 Dec;53(6):963-978. Epub 2020 Mar 26 doi: 10.1016/j.jmii.2020.03.007. PMID: 32265181
Fergus KB, Lee AW, Baradaran N, Cohen AJ, Stohr BA, Erickson BA, Mmonu NA, Breyer BN
Urology 2020 Jan;135:11-19. Epub 2019 Oct 9 doi: 10.1016/j.urology.2019.09.034. PMID: 31605681

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