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Immunodeficiency 81(IMD81)

MedGen UID:
1788669
Concept ID:
C5543540
Disease or Syndrome
Synonyms: IMD81; IMMUNODEFICIENCY 81
 
Gene (location): LCP2 (5q35.1)
 
Monarch Initiative: MONDO:0030302
OMIM®: 619374

Definition

Immunodeficiency-81 (IMD81) is an autosomal recessive complex immunologic disorder with onset of symptoms in infancy. The phenotype is highly variable and may include both immunodeficiency with recurrent infections, including bacterial and fungal infections, as well as autoimmune features, including autoimmune hemolytic anemia, pancytopenia, thrombocytopenia, and inflammatory bowel disease. Immunologic workup shows immune dysregulation with abnormalities affecting multiple immune cell lineages, including T cells, B cells, NK cells, and neutrophils, which may be decreased or increased and demonstrate functional deficits. There is a wide range of hematologic abnormalities. Affected individuals may be susceptible to severe EBV infection. The disorder is caused by a defect in intracellular immune signaling pathways (summary by Lev et al., 2021; Edwards et al., 2023). [from OMIM]

Clinical features

From HPO
Impaired collagen-induced platelet aggregation
MedGen UID:
870264
Concept ID:
C4024703
Finding
Abnormal response to collagen or collagen-mimetics as manifested by reduced or lacking aggregation of platelets upon addition collagen or collagen-mimetics.
Abscess
MedGen UID:
1684
Concept ID:
C0000833
Disease or Syndrome
An abscess is a localized collection of purulent material surrounded by inflammation and granulation.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Reduced natural killer cell activity
MedGen UID:
333452
Concept ID:
C1839969
Finding
Reduced ability of the natural killer cell to function in the adaptive immune response.
Recurrent cutaneous abscess formation
MedGen UID:
867572
Concept ID:
C4021957
Finding
An increased susceptibility to cutaneous abscess formation, as manifested by a medical history of recurrent cutaneous abscesses.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
Impaired neutrophil chemotaxis
MedGen UID:
895851
Concept ID:
C4280709
Cell or Molecular Dysfunction
An impairment of the migration of neutrophils towards chemoattractants as part of the innate immune response
Abnormally low T cell receptor excision circle level
MedGen UID:
1611921
Concept ID:
C4531052
Finding
Reduced level of T cell receptor excision circle (TRECs) as measured by the TREC assay. Late in maturation, 70% of thymocytes that will ultimately express alpha/beta-T cell receptors form a circular DNA TREC from the excised TCRdelta gene that lies within the TCRalpha genetic locus. The circles are stable but do not increase following cell division and, therefore, become diluted as T cells proliferate. A quantitative polymerase chain reaction (PCR) reaction across the joint of the circular DNA provides the TREC copy number, a marker of newly-formed, antigenically-naïve thymic emigrant T cells.
Reduced antigen-specific T cell proliferation
MedGen UID:
1621145
Concept ID:
C4531148
Finding
Impaired proliferation and expansion of a T cell population following activation by an antigenic stimulus.
Decreased proportion of CD4-positive T cells
MedGen UID:
1698933
Concept ID:
C5139203
Finding
A reduction in the proportion of CD4-positive T cells relative to the total number of T cells.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Petechiae
MedGen UID:
10680
Concept ID:
C0031256
Disease or Syndrome
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
Reduced reactive oxygen species production in neutrophils
MedGen UID:
1698992
Concept ID:
C5139101
Cell or Molecular Dysfunction
An abnormal reduction in the amount of reactive oxygen produced by neutrophils in the respiratory burst.

Professional guidelines

PubMed

Muller WJ
Pediatr Res 2017 Jan;81(1-2):162-169. Epub 2016 Sep 27 doi: 10.1038/pr.2016.191. PMID: 27673425
van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM
J Clin Immunol 2015 May;35(4):416-30. Epub 2015 Apr 17 doi: 10.1007/s10875-015-0152-6. PMID: 25893636Free PMC Article
Chu C, Selwyn PA
Am Fam Physician 2010 May 15;81(10):1239-44. PMID: 20507048

Recent clinical studies

Etiology

Agress A, Oprea Y, Roy S, Strauch C, Rosenstreich D, Ferastraoaru D
J Allergy Clin Immunol Pract 2024 Jan;12(1):185-194. Epub 2023 Oct 19 doi: 10.1016/j.jaip.2023.10.026. PMID: 37863316
Borte M, Hanitsch LG, Mahlaoui N, Fasshauer M, Huscher D, Speletas M, Dimou M, Kamieniak M, Hermann C, Pittrow D, Milito C
J Clin Immunol 2023 Aug;43(6):1259-1271. Epub 2023 Apr 10 doi: 10.1007/s10875-023-01470-2. PMID: 37036560Free PMC Article
Getahun H, Gunneberg C, Granich R, Nunn P
Clin Infect Dis 2010 May 15;50 Suppl 3:S201-7. doi: 10.1086/651492. PMID: 20397949
Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, Temesgen Z
Mayo Clin Proc 2006 Feb;81(2):213-9. doi: 10.4065/81.2.213. PMID: 16471077
Bamberger JD, Waldo CR, Gerberding JL, Katz MH
Am J Med 1999 Mar;106(3):323-6. doi: 10.1016/s0002-9343(99)00018-2. PMID: 10190382

Diagnosis

Nduaguba SO, Ford KH, Wilson JP, Lawson KA
AIDS Care 2021 Mar;33(3):285-289. Epub 2019 Dec 15 doi: 10.1080/09540121.2019.1703890. PMID: 31838894
Agarwal S, Cunningham-Rundles C
Immunol Allergy Clin North Am 2019 Feb;39(1):81-94. doi: 10.1016/j.iac.2018.08.006. PMID: 30466774Free PMC Article
Chu C, Selwyn PA
Am Fam Physician 2010 May 15;81(10):1239-44. PMID: 20507048
Phelan JA
Med Clin North Am 1997 Mar;81(2):511-31. doi: 10.1016/s0025-7125(05)70529-0. PMID: 9093240
French AL, Benator DA, Gordin FM
Med Clin North Am 1997 Mar;81(2):361-79. doi: 10.1016/s0025-7125(05)70522-8. PMID: 9093233

Therapy

Prather C, Jeon C
Am J Health Syst Pharm 2022 Oct 21;79(21):1898-1905. doi: 10.1093/ajhp/zxac201. PMID: 35894204
Temfack E, Boyer-Chammard T, Lawrence D, Delliere S, Loyse A, Lanternier F, Alanio A, Lortholary O
Curr Neurol Neurosci Rep 2019 Oct 31;19(10):81. doi: 10.1007/s11910-019-0993-0. PMID: 31673881
Wiysonge CS, Ndze VN, Kongnyuy EJ, Shey MS
Cochrane Database Syst Rev 2017 Sep 7;9(9):CD003648. doi: 10.1002/14651858.CD003648.pub4. PMID: 28880995Free PMC Article
Mason-Jones AJ, Sinclair D, Mathews C, Kagee A, Hillman A, Lombard C
Cochrane Database Syst Rev 2016 Nov 8;11(11):CD006417. doi: 10.1002/14651858.CD006417.pub3. PMID: 27824221Free PMC Article
Shelton MJ, O'Donnell AM, Morse GD
Ann Pharmacother 1992 May;26(5):660-70. doi: 10.1177/106002809202600511. PMID: 1350471

Prognosis

Vallée TC, Glasmacher JS, Buchner H, Arkwright PD, Behrends U, Bondarenko A, Browning MJ, Buchbinder D, Cattoni A, Chernyshova L, Ciznar P, Cole T, Czogała W, Dueckers G, Edgar JDM, Erbey F, Fasth A, Ferrua F, Formankova R, Gambineri E, Gennery AR, Goldman FD, Gonzalez-Granado LI, Heilmann C, Heiskanen-Kosma T, Juntti H, Kainulainen L, Kanegane H, Karaca NE, Kilic SS, Klein C, Kołtan S, Kondratenko I, Meyts I, Nasrullayeva GM, Notarangelo LD, Pasic S, Pellier I, Pignata C, Misbah S, Schulz A, Segundo GR, Shcherbina A, Slatter M, Sokolic R, Soler-Palacin P, Stepensky P, van Montfrans JM, Ryhänen S, Wolska-Kuśnierz B, Ziegler JB, Zhao X, Aiuti A, Ochs HD, Albert MH
Blood 2024 Jun 13;143(24):2504-2516. doi: 10.1182/blood.2023021411. PMID: 38579284
Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC
Lancet HIV 2024 Mar;11(3):e176-e185. Epub 2024 Jan 24 doi: 10.1016/S2352-3018(23)00272-2. PMID: 38280393
Bassat Q, Blau DM, Ogbuanu IU, Samura S, Kaluma E, Bassey IA, Sow S, Keita AM, Tapia MD, Mehta A, Kotloff KL, Rahman A, Islam KM, Alam M, El Arifeen S, Gurley ES, Baillie V, Mutevedzi P, Mahtab S, Thwala BN, Tippett Barr BA, Onyango D, Akelo V, Rogena E, Onyango P, Omore R, Mandomando I, Ajanovic S, Varo R, Sitoe A, Duran-Frigola M, Assefa N, Scott JAG, Madrid L, Tesfaye T, Dessie Y, Madewell ZJ, Breiman RF, Whitney CG, Madhi SA; Child Health and Mortality Prevention Surveillance (CHAMPS) Network
JAMA Netw Open 2023 Jul 3;6(7):e2322494. doi: 10.1001/jamanetworkopen.2023.22494. PMID: 37494044Free PMC Article
Park SY, Faraci G, Murphy G, Pilcher C, Busch MP, Lee HY
J Infect Dis 2021 Sep 17;224(6):1048-1059. doi: 10.1093/infdis/jiab060. PMID: 33517458Free PMC Article
GBD 2017 HIV collaborators
Lancet HIV 2019 Dec;6(12):e831-e859. Epub 2019 Aug 19 doi: 10.1016/S2352-3018(19)30196-1. PMID: 31439534Free PMC Article

Clinical prediction guides

Borte M, Hanitsch LG, Mahlaoui N, Fasshauer M, Huscher D, Speletas M, Dimou M, Kamieniak M, Hermann C, Pittrow D, Milito C
J Clin Immunol 2023 Aug;43(6):1259-1271. Epub 2023 Apr 10 doi: 10.1007/s10875-023-01470-2. PMID: 37036560Free PMC Article
Shi Y, Wang C
Front Immunol 2021;12:679556. Epub 2021 May 25 doi: 10.3389/fimmu.2021.679556. PMID: 34113351Free PMC Article
Kaulen LD, Galluzzo D, Hui P, Barbiero F, Karschnia P, Huttner A, Fulbright R, Baehring JM
J Neurooncol 2019 Aug;144(1):107-115. Epub 2019 Jun 13 doi: 10.1007/s11060-019-03208-w. PMID: 31190317
Bruno G, Saracino A, Monno L, Angarano G
AIDS Rev 2017 Apr-Jun;19(2):81-88. PMID: 28182620
Writing Committee for the CASCADE Collaboration
Arch Intern Med 2011 Sep 26;171(17):1560-9. doi: 10.1001/archinternmed.2011.401. PMID: 21949165Free PMC Article

Recent systematic reviews

Wang W, Zhao S, Wu Y, Duan W, Li S, Li Z, Guo C, Wang W, Zhang T, Wu H, Huang X
JMIR Public Health Surveill 2023 Jul 27;9:e46767. doi: 10.2196/46767. PMID: 37498645Free PMC Article
Wu S, Wang J, Guo Q, Lan H, Sun Y, Ren M, Liu Y, Wang P, Wang L, Su R, Zhang J, Chen Y, Li G
Clin Microbiol Infect 2023 Aug;29(8):1000-1007. Epub 2023 Mar 13 doi: 10.1016/j.cmi.2023.03.002. PMID: 36921717
Clarke MA, Deshmukh AA, Suk R, Roberts J, Gilson R, Jay N, Stier EA, Wentzensen N
Int J Cancer 2022 Dec 1;151(11):1889-1901. Epub 2022 Aug 6 doi: 10.1002/ijc.34199. PMID: 35793241Free PMC Article
Yimer NB, Mohammed MA, Solomon K, Tadese M, Grutzmacher S, Meikena HK, Alemnew B, Sharew NT, Habtewold TD
Public Health 2021 Jun;195:105-111. Epub 2021 May 31 doi: 10.1016/j.puhe.2021.04.014. PMID: 34082174
Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, Krymskaya VP, Kelleher D, Rubenstein AH, Fajgenbaum DC
Lancet Haematol 2016 Apr;3(4):e163-75. Epub 2016 Mar 17 doi: 10.1016/S2352-3026(16)00006-5. PMID: 27063975

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