U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Immunodeficiency 75(IMD75)

MedGen UID:
1741014
Concept ID:
C5436860
Disease or Syndrome
Synonym: IMMUNODEFICIENCY 75 WITH LYMPHOPROLIFERATION
 
Gene (location): TET2 (4q24)
 
Monarch Initiative: MONDO:0030858
OMIM®: 619126

Definition

Immunodeficiency-75 with lymphoproliferation (IMD75) is an autosomal recessive immunologic disorder characterized by immunodeficiency, immune dysregulation, and the development of lymphoproliferative disorders, including lymphoma. Affected individuals usually present in infancy with severe and recurrent infections, mainly viral and affecting the respiratory tract. Some patients may have autoimmune cytopenias, anemia, or thrombocytopenia. Patients also develop hepatosplenomegaly, lymphadenopathy, lymphoproliferative disorders, and various types of T- or B-cell lymphomas. Immunologic work-up shows decreased class-switched B cells, impaired B-cell terminal differentiation, and hypo- or hypergammaglobulinemia. There is skewed differentiation and dysregulation of T cells, as well as possibly disrupted hematopoiesis. Additional features include failure to thrive and global developmental delay. The phenotype may be reminiscent of ALPS (601859), including laboratory evidence of impaired Fas-dependent T-cell apoptosis. Although hematopoietic stem cell transplantation may be effective treatment, many patients die in childhood (summary by Stremenova Spegarova et al., 2020). [from OMIM]

Clinical features

From HPO
Lymphoma
MedGen UID:
44223
Concept ID:
C0024299
Neoplastic Process
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Moderate global developmental delay
MedGen UID:
500807
Concept ID:
C2237142
Finding
A moderate delay in the achievement of motor or mental milestones in the domains of development of a child.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Persistent EBV viremia
MedGen UID:
767466
Concept ID:
C3554552
Finding
Persistent presence of Epstein-Barr virus in the blood.
Follicular hyperplasia
MedGen UID:
863170
Concept ID:
C4014733
Finding
Lymphadenopathy (enlargement of lymph nodes) owing to hyperplasia of follicular (germinal) centers.
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.
Decreased FasL-mediated apoptosis
MedGen UID:
1788667
Concept ID:
C5539888
Cell or Molecular Dysfunction
A reduced amount of programmed cell death upon stimulation of the FAS receptor, which normally induces caspase-8 dependent apoptosis.

Professional guidelines

PubMed

Ochoa S, Abers MS, Rosen LB, Rump A, Howe K, Lieberman JA, Wright BL, Suez D, Krausz M, Grimbacher B, Lionakis MS, Uzel G
Blood Adv 2023 Oct 10;7(19):5743-5751. doi: 10.1182/bloodadvances.2023010105. PMID: 37406177Free PMC Article
Hashempour T, Moayedi J, Mousavi Z, Esmaeli M, Asadzadeh A, Hasanshahi Z, Dehghani B
Lab Med 2021 Jul 1;52(4):369-374. doi: 10.1093/labmed/lmaa106. PMID: 33345285
Benedikt C, Kelly SL, Wilson D, Wilson DP; Optima Consortium
Int J Drug Policy 2016 Dec;38:73-80. Epub 2016 Nov 22 doi: 10.1016/j.drugpo.2016.10.011. PMID: 27883944

Recent clinical studies

Etiology

Zhang B, Fan J, Huang C, Fan H, Chen J, Huang X, Zeng X
J Clin Immunol 2023 Oct;43(7):1660-1670. Epub 2023 Jun 26 doi: 10.1007/s10875-023-01537-0. PMID: 37365453Free PMC Article
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Deeks SG, Overbaugh J, Phillips A, Buchbinder S
Nat Rev Dis Primers 2015 Oct 1;1:15035. doi: 10.1038/nrdp.2015.35. PMID: 27188527
Schuman P, Sobel JD
Aust N Z J Obstet Gynaecol 1993 Nov;33(4):341-50. doi: 10.1111/j.1479-828x.1993.tb02106.x. PMID: 8179538
Gayle HD, D'Angelo LJ
Pediatr Infect Dis J 1991 Apr;10(4):322-8. doi: 10.1097/00006454-199104000-00012. PMID: 2062630

Diagnosis

Bonilla FA
Allergy Asthma Proc 2020 Jan 1;41(1):19-25. doi: 10.2500/aap.2020.41.190012. PMID: 31888779
Karthikeyan K
Indian J Dermatol Venereol Leprol 2009 Jul-Aug;75(4):340-7. doi: 10.4103/0378-6323.53128. PMID: 19584457
Scarlatti G
Lancet 1996 Sep 28;348(9031):863-8. doi: 10.1016/S0140-6736(95)11030-5. PMID: 8826814
Schuman P, Sobel JD
Aust N Z J Obstet Gynaecol 1993 Nov;33(4):341-50. doi: 10.1111/j.1479-828x.1993.tb02106.x. PMID: 8179538
Shannon KM, Ammann AJ
J Pediatr 1985 Feb;106(2):332-42. doi: 10.1016/s0022-3476(85)80320-6. PMID: 2982008

Therapy

Grinspoon SK, Fitch KV, Overton ET, Fichtenbaum CJ, Zanni MV, Aberg JA, Malvestutto C, Lu MT, Currier JS, Sponseller CA, Waclawiw M, Alston-Smith B, Cooper-Arnold K, Klingman KL, Desvigne-Nickens P, Hoffmann U, Ribaudo HJ, Douglas PS; REPRIEVE Investigators
Am Heart J 2019 Jun;212:23-35. Epub 2019 Mar 4 doi: 10.1016/j.ahj.2018.12.016. PMID: 30928825Free PMC Article
Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G, Dangond F, Adeniji AK, Vermersch P
Mult Scler 2018 Oct;24(12):1594-1604. Epub 2017 Sep 5 doi: 10.1177/1352458517727603. PMID: 28870107
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Deeks SG, Overbaugh J, Phillips A, Buchbinder S
Nat Rev Dis Primers 2015 Oct 1;1:15035. doi: 10.1038/nrdp.2015.35. PMID: 27188527
Penazzato M, Dominguez K, Cotton M, Barlow-Mosha L, Ford N
Clin Infect Dis 2015 Jun 1;60 Suppl 3:S177-81. doi: 10.1093/cid/civ110. PMID: 25972500

Prognosis

Zhang B, Fan J, Huang C, Fan H, Chen J, Huang X, Zeng X
J Clin Immunol 2023 Oct;43(7):1660-1670. Epub 2023 Jun 26 doi: 10.1007/s10875-023-01537-0. PMID: 37365453Free PMC Article
Senefeld JW, Klassen SA, Ford SK, Senese KA, Wiggins CC, Bostrom BC, Thompson MA, Baker SE, Nicholson WT, Johnson PW, Carter RE, Henderson JP, Hartman WR, Pirofski LA, Wright RS, Fairweather L, Bruno KA, Paneth NS, Casadevall A, Joyner MJ
Transfusion 2021 Aug;61(8):2503-2511. Epub 2021 Jun 1 doi: 10.1111/trf.16525. PMID: 34036587Free PMC Article
Garg RK
Acta Neurol Scand 2010 Aug;122(2):75-90. Epub 2010 Jan 6 doi: 10.1111/j.1600-0404.2009.01316.x. PMID: 20055767
Saharan S, Lodha R, Agarwal R, Deorari AK, Paul VK
Indian J Pediatr 2008 Apr;75(4):359-62. Epub 2008 May 18 doi: 10.1007/s12098-008-0039-0. PMID: 18536891
Schuman P, Sobel JD
Aust N Z J Obstet Gynaecol 1993 Nov;33(4):341-50. doi: 10.1111/j.1479-828x.1993.tb02106.x. PMID: 8179538

Clinical prediction guides

Asai N, Motojima S, Ohkuni Y, Matsunuma R, Nakashita T, Kaneko N, Mikamo H
Respir Investig 2022 Jul;60(4):522-530. Epub 2022 Apr 29 doi: 10.1016/j.resinv.2022.04.002. PMID: 35501264
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CA, Oliveira JB, Kiss MH
J Clin Immunol 2008 May;28 Suppl 1:S34-41. Epub 2008 Apr 11 doi: 10.1007/s10875-008-9187-2. PMID: 18404362
Schuman P, Sobel JD
Aust N Z J Obstet Gynaecol 1993 Nov;33(4):341-50. doi: 10.1111/j.1479-828x.1993.tb02106.x. PMID: 8179538
Shannon KM, Ammann AJ
J Pediatr 1985 Feb;106(2):332-42. doi: 10.1016/s0022-3476(85)80320-6. PMID: 2982008

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
Sultana ZZ, Hoque FU, Beyene J, Akhlak-Ul-Islam M, Khan MHR, Ahmed S, Hawlader DH, Hossain A
BMC Infect Dis 2021 Jan 11;21(1):51. doi: 10.1186/s12879-020-05749-2. PMID: 33430786Free PMC Article
Hemelaar J, Elangovan R, Yun J, Dickson-Tetteh L, Fleminger I, Kirtley S, Williams B, Gouws-Williams E, Ghys PD; WHO–UNAIDS Network for HIV Isolation Characterisation
Lancet Infect Dis 2019 Feb;19(2):143-155. Epub 2018 Nov 30 doi: 10.1016/S1473-3099(18)30647-9. PMID: 30509777
Degenhardt L, Peacock A, Colledge S, Leung J, Grebely J, Vickerman P, Stone J, Cunningham EB, Trickey A, Dumchev K, Lynskey M, Griffiths P, Mattick RP, Hickman M, Larney S
Lancet Glob Health 2017 Dec;5(12):e1192-e1207. Epub 2017 Oct 23 doi: 10.1016/S2214-109X(17)30375-3. PMID: 29074409Free PMC Article
Prasad K, Singh MB, Ryan H
Cochrane Database Syst Rev 2016 Apr 28;4(4):CD002244. doi: 10.1002/14651858.CD002244.pub4. PMID: 27121755Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...