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Immunodeficiency 112(IMD112)

MedGen UID:
1841269
•Concept ID:
C5830633
•
Disease or Syndrome
Synonym: IMD112
 
Gene (location): MAP3K14 (17q21.31)
 
Monarch Initiative: MONDO:0957535
OMIM®: 620449

Definition

Immunodeficiency-112 (IMD112) is an autosomal recessive primary immunologic disorder with variable manifestations beginning in early childhood. Some patients have recurrent bacterial, viral, and fungal infections, including disseminated bacillus Calmette-Guerin (BCG)-related infections, whereas at least 1 patient only presented with BCG-related infections. Immunologic workup shows variable abnormalities affecting lymphoid immunity, including hypogammaglobulinemia, lymphopenia or paradoxical lymphocytosis, and defects in B, T, and NK cell differentiation and function mainly due to disruption of the noncanonical NFKB (see 164011) signaling pathway (Willmann et al., 2014; Schlechter et al., 2017). [from OMIM]

Clinical features

From HPO
Chronic diarrhea
MedGen UID:
96036
•Concept ID:
C0401151
•
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
See: Feature record | Search on this feature
Recurrent lower respiratory tract infections
MedGen UID:
756211
•Concept ID:
C3163798
•
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
See: Feature record | Search on this feature
Chronic mucocutaneous candidiasis
MedGen UID:
2426
•Concept ID:
C0006845
•
Disease or Syndrome
Recurrent or persistent superficial Candida infections of the skin, mucous membranes, and nails.
See: Feature record | Search on this feature
Decreased circulating IgA concentration
MedGen UID:
57934
•Concept ID:
C0162538
•
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
See: Feature record | Search on this feature
Decreased circulating total IgM
MedGen UID:
116095
•Concept ID:
C0239989
•
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
See: Feature record | Search on this feature
Recurrent viral infections
MedGen UID:
332357
•Concept ID:
C1837066
•
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
See: Feature record | Search on this feature
Recurrent bacterial infections
MedGen UID:
334943
•Concept ID:
C1844383
•
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
See: Feature record | Search on this feature
B lymphocytopenia
MedGen UID:
340780
•Concept ID:
C1855067
•
Finding
An abnormal decrease from the normal count of B cells.
See: Feature record | Search on this feature
Reduced natural killer cell count
MedGen UID:
383765
•Concept ID:
C1855767
•
Finding
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system with an ability to mediate cytotoxicity and produce cytokines after the ligation of a germline-encoded activation receptor.
See: Feature record | Search on this feature
Increased B cell count
MedGen UID:
349067
•Concept ID:
C1858972
•
Finding
An abnormal increase from the normal count of B cells.
See: Feature record | Search on this feature
T lymphocytopenia
MedGen UID:
419385
•Concept ID:
C2931322
•
Finding
An abnormally low count of T cells.
See: Feature record | Search on this feature
BCGosis
MedGen UID:
823215
•Concept ID:
C3830467
•
Disease or Syndrome
Distant, or disseminated infection with Bacillus Calmette-Guerin (BCG) following vaccination associated with failure to contain thebacillus Calmette-Guerin (BCG) following vaccination leading to spread of BCG to many sites in the body. The tuberculosis vaccine BCG contains live attenuated Mycobacterium bovis.
See: Feature record | Search on this feature
Increased T cell count
MedGen UID:
867575
•Concept ID:
C4021960
•
Finding
An abnormal increase in the total number of T cells detected in the blood.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
BCGitis
MedGen UID:
1684722
•Concept ID:
C5139070
•
Disease or Syndrome
Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination.
See: Feature record | Search on this feature
Decreased circulating IgG concentration
MedGen UID:
1720114
•Concept ID:
C5234937
•
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
See: Feature record | Search on this feature
Decreased proportion of gamma-delta T cells
MedGen UID:
1713360
•Concept ID:
C5398020
•
Finding
Decreased proportion of gamma-delta T cells relative to the total number of T cells.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

HIV Treatment Outcomes in POP-UP: Drop-in HIV Primary Care Model for People Experiencing Homelessness.
Hickey MD, Imbert E, Appa A, Del Rosario JB, Lynch E, Friend J, Avila R, Clemenzi-Allen A, Riley ED, Gandhi M, Havlir DV
J Infect Dis 2022 Oct 7;226(Suppl 3):S353-S362. doi: 10.1093/infdis/jiac267. PMID: 35759251Free PMC Article
Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario.
Yadav RM, Gupta M, Dalvi A, Bargir UA, Hule G, Shabrish S, Aluri J, Kulkarni M, Kambli P, Uppuluri R, Seshadri S, Jagadeesh S, Suresh B, Raja J, Taur P, Malaischamy S, Ghosh P, Mahalingam S, Kadam P, Lashkari HP, Tamhankar P, Tamhankar V, Mithbawkar S, Bhattad S, Jhawar P, Makam A, Bansal V, Prasad M, Govindaraj G, Guhan B, Bharadwaj Tallapaka K, Desai M, Raj R, Madkaikar MR
Front Immunol 2020;11:612316. Epub 2020 Dec 7 doi: 10.3389/fimmu.2020.612316. PMID: 33365035Free PMC Article
Care and management of the infant of the HIV-1-infected mother.
Paintsil E, Andiman WA
Semin Perinatol 2007 Apr;31(2):112-23. doi: 10.1053/j.semperi.2007.02.007. PMID: 17462496

Recent clinical studies

Etiology

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.
Sobieszczyk ME, Mannheimer S, Paez CA, Yu C, Gamble T, Theodore DA, Chege W, Yacovone M, Hanscom B, Heptinstall J, Seaton KE, Zhang L, Miner MD, Eaton A, Weiner JA, Mayer K, Kalams S, Stephenson K, Julg B, Caskey M, Nussenzweig M, Gama L, Barouch DH, Ackerman ME, Tomaras GD, Huang Y, Montefiori D; HVTN 130/HPTN 089 Study Team
Lancet HIV 2023 Oct;10(10):e653-e662. doi: 10.1016/S2352-3018(23)00140-6. PMID: 37802566Free PMC Article
Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.
Ando N, Mizushima D, Omata K, Nemoto T, Inamura N, Hiramoto S, Takano M, Aoki T, Watanabe K, Uemura H, Shiojiri D, Yanagawa Y, Tanuma J, Teruya K, Kikuchi Y, Gatanaga H, Oka S
Clin Infect Dis 2023 Sep 11;77(5):779-787. doi: 10.1093/cid/ciad278. PMID: 37157863
The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis.
Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, Meya DB, Chiller TM, Boulware DR
Lancet Infect Dis 2022 Dec;22(12):1748-1755. Epub 2022 Aug 29 doi: 10.1016/S1473-3099(22)00499-6. PMID: 36049486Free PMC Article
TB-related deaths among adults in Guinea-Bissau.
Kühle AJ, Patsche CB, Fløe A, Sifna A, Gomes V, Wejse C, Rudolf F
Int J Tuberc Lung Dis 2022 Jul 1;26(7):664-670. doi: 10.5588/ijtld.21.0483. PMID: 35768921
Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.
Anglemyer A, Rutherford GW, Horvath T, Baggaley RC, Egger M, Siegfried N
Cochrane Database Syst Rev 2013 Apr 30;2013(4):CD009153. doi: 10.1002/14651858.CD009153.pub3. PMID: 23633367Free PMC Article

Diagnosis

The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis.
Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, Meya DB, Chiller TM, Boulware DR
Lancet Infect Dis 2022 Dec;22(12):1748-1755. Epub 2022 Aug 29 doi: 10.1016/S1473-3099(22)00499-6. PMID: 36049486Free PMC Article
TB-related deaths among adults in Guinea-Bissau.
Kühle AJ, Patsche CB, Fløe A, Sifna A, Gomes V, Wejse C, Rudolf F
Int J Tuberc Lung Dis 2022 Jul 1;26(7):664-670. doi: 10.5588/ijtld.21.0483. PMID: 35768921
Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario.
Yadav RM, Gupta M, Dalvi A, Bargir UA, Hule G, Shabrish S, Aluri J, Kulkarni M, Kambli P, Uppuluri R, Seshadri S, Jagadeesh S, Suresh B, Raja J, Taur P, Malaischamy S, Ghosh P, Mahalingam S, Kadam P, Lashkari HP, Tamhankar P, Tamhankar V, Mithbawkar S, Bhattad S, Jhawar P, Makam A, Bansal V, Prasad M, Govindaraj G, Guhan B, Bharadwaj Tallapaka K, Desai M, Raj R, Madkaikar MR
Front Immunol 2020;11:612316. Epub 2020 Dec 7 doi: 10.3389/fimmu.2020.612316. PMID: 33365035Free PMC Article
HIV testing: What, where and how?
Santella AJ, Majam M, Van Ngo H, Luis H
Oral Dis 2020 Sep;26 Suppl 1:112-116. doi: 10.1111/odi.13392. PMID: 32862529
Skin manifestations of primary immune deficiency.
Lehman H
Clin Rev Allergy Immunol 2014 Apr;46(2):112-9. doi: 10.1007/s12016-013-8377-8. PMID: 23760761

Therapy

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.
Sobieszczyk ME, Mannheimer S, Paez CA, Yu C, Gamble T, Theodore DA, Chege W, Yacovone M, Hanscom B, Heptinstall J, Seaton KE, Zhang L, Miner MD, Eaton A, Weiner JA, Mayer K, Kalams S, Stephenson K, Julg B, Caskey M, Nussenzweig M, Gama L, Barouch DH, Ackerman ME, Tomaras GD, Huang Y, Montefiori D; HVTN 130/HPTN 089 Study Team
Lancet HIV 2023 Oct;10(10):e653-e662. doi: 10.1016/S2352-3018(23)00140-6. PMID: 37802566Free PMC Article
Video-Based Educational Interventions for Patients With Chronic Illnesses: Systematic Review.
Deshpande N, Wu M, Kelly C, Woodrick N, Werner DA, Volerman A, Press VG
J Med Internet Res 2023 Jul 19;25:e41092. doi: 10.2196/41092. PMID: 37467015Free PMC Article
Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.
Ando N, Mizushima D, Omata K, Nemoto T, Inamura N, Hiramoto S, Takano M, Aoki T, Watanabe K, Uemura H, Shiojiri D, Yanagawa Y, Tanuma J, Teruya K, Kikuchi Y, Gatanaga H, Oka S
Clin Infect Dis 2023 Sep 11;77(5):779-787. doi: 10.1093/cid/ciad278. PMID: 37157863
Efficacy and Safety of Switching to Dolutegravir/Lamivudine Versus Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Results Through Week 144 From the Phase 3, Noninferiority TANGO Randomized Trial.
Osiyemi O, De Wit S, Ajana F, Bisshop F, Portilla J, Routy JP, Wyen C, Ait-Khaled M, Leone P, Pappa KA, Wang R, Wright J, George N, Wynne B, Aboud M, van Wyk J, Smith KY
Clin Infect Dis 2022 Sep 29;75(6):975-986. doi: 10.1093/cid/ciac036. PMID: 35079789Free PMC Article
Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.
Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, Chen AL, Li SY, Zhuo C, Deng XL, Cheng FJ, Gao Y, Zhang JH, Xie JX, Peng H, Li YX, Wu XX, Liu W, Peng H, Wang J, Xiao GM, Chen PY, Wang CY, Yang ZF, Zhao JC, Zhong NS
JAMA Intern Med 2021 Jan 1;181(1):71-78. doi: 10.1001/jamainternmed.2020.5503. PMID: 32910179Free PMC Article

Prognosis

TB-related deaths among adults in Guinea-Bissau.
Kühle AJ, Patsche CB, Fløe A, Sifna A, Gomes V, Wejse C, Rudolf F
Int J Tuberc Lung Dis 2022 Jul 1;26(7):664-670. doi: 10.5588/ijtld.21.0483. PMID: 35768921
Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.
Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, Chen AL, Li SY, Zhuo C, Deng XL, Cheng FJ, Gao Y, Zhang JH, Xie JX, Peng H, Li YX, Wu XX, Liu W, Peng H, Wang J, Xiao GM, Chen PY, Wang CY, Yang ZF, Zhao JC, Zhong NS
JAMA Intern Med 2021 Jan 1;181(1):71-78. doi: 10.1001/jamainternmed.2020.5503. PMID: 32910179Free PMC Article
HCV adaptation to HIV coinfection.
Lara J, Teka MA, Sims S, Xia GL, Ramachandran S, Khudyakov Y
Infect Genet Evol 2018 Nov;65:216-225. Epub 2018 Jul 31 doi: 10.1016/j.meegid.2018.07.039. PMID: 30075255
B lymphocytes: how they develop and function.
LeBien TW, Tedder TF
Blood 2008 Sep 1;112(5):1570-80. doi: 10.1182/blood-2008-02-078071. PMID: 18725575Free PMC Article
Primary colonic lymphoma.
Doolabh N, Anthony T, Simmang C, Bieligk S, Lee E, Huber P, Hughes R, Turnage R
J Surg Oncol 2000 Aug;74(4):257-62. doi: 10.1002/1096-9098(200008)74:4<257::aid-jso3>3.0.co;2-u. PMID: 10962456

Clinical prediction guides

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.
Sobieszczyk ME, Mannheimer S, Paez CA, Yu C, Gamble T, Theodore DA, Chege W, Yacovone M, Hanscom B, Heptinstall J, Seaton KE, Zhang L, Miner MD, Eaton A, Weiner JA, Mayer K, Kalams S, Stephenson K, Julg B, Caskey M, Nussenzweig M, Gama L, Barouch DH, Ackerman ME, Tomaras GD, Huang Y, Montefiori D; HVTN 130/HPTN 089 Study Team
Lancet HIV 2023 Oct;10(10):e653-e662. doi: 10.1016/S2352-3018(23)00140-6. PMID: 37802566Free PMC Article
HCV adaptation to HIV coinfection.
Lara J, Teka MA, Sims S, Xia GL, Ramachandran S, Khudyakov Y
Infect Genet Evol 2018 Nov;65:216-225. Epub 2018 Jul 31 doi: 10.1016/j.meegid.2018.07.039. PMID: 30075255
Clinical and Microbiological Features of Salmonella Meningitis in a South African Population, 2003-2013.
Keddy KH, Sooka A, Musekiwa A, Smith AM, Ismail H, Tau NP, Crowther-Gibson P, Angulo FJ, Klugman KP; Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA)
Clin Infect Dis 2015 Nov 1;61 Suppl 4(Suppl 4):S272-82. doi: 10.1093/cid/civ685. PMID: 26449942Free PMC Article
Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.
Anglemyer A, Rutherford GW, Horvath T, Baggaley RC, Egger M, Siegfried N
Cochrane Database Syst Rev 2013 Apr 30;2013(4):CD009153. doi: 10.1002/14651858.CD009153.pub3. PMID: 23633367Free PMC Article
B lymphocytes: how they develop and function.
LeBien TW, Tedder TF
Blood 2008 Sep 1;112(5):1570-80. doi: 10.1182/blood-2008-02-078071. PMID: 18725575Free PMC Article

Recent systematic reviews

Video-Based Educational Interventions for Patients With Chronic Illnesses: Systematic Review.
Deshpande N, Wu M, Kelly C, Woodrick N, Werner DA, Volerman A, Press VG
J Med Internet Res 2023 Jul 19;25:e41092. doi: 10.2196/41092. PMID: 37467015Free PMC Article
Comparison of Different Anti-Demodex Strategies: A Systematic Review and Meta-Analysis.
Li J, Wei E, Reisinger A, French LE, Clanner-Engelshofen BM, Reinholz M
Dermatology 2023;239(1):12-31. Epub 2022 Oct 28 doi: 10.1159/000526296. PMID: 36310014
Risk factors for Clostridioides difficile infection in children: a systematic review and meta-analysis.
Dong N, Li ZR, Qin P, Qiang CX, Yang J, Niu YN, Niu XR, Liu XX, Wang WG, Wen BJ, Ouyang ZR, Zhang YL, Zhao M, Li JYR, Zhao JH
J Hosp Infect 2022 Dec;130:112-121. Epub 2022 Sep 13 doi: 10.1016/j.jhin.2022.09.004. PMID: 36108754
Breastfeeding Outcomes and Associated Risks in HIV-Infected and HIV-Exposed Infants: A Systematic Review.
Eccles R, du Toit M, de Jongh G, Krüger E
Breastfeed Med 2022 Feb;17(2):112-130. Epub 2021 Dec 21 doi: 10.1089/bfm.2021.0107. PMID: 34936484
Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.
Wei F, Gaisa MM, D'Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Donà MG, Goldstone SE, Schim van der Loeff MF, Neukam K, Meites E, Poynten IM, Dai J, Combes JD, Wieland U, Burgos J, Wilkin TJ, Hernandez AL, Iribarren Díaz M, Hidalgo-Tenorio C, Valencia Arredondo M, Nyitray AG, Wentzensen N, Chow EP, Smelov V, Nowak RG, Phanuphak N, Woo YL, Choi Y, Hu Y, Schofield AM, Woestenberg PJ, Chikandiwa AT, Hickey AC, de Pokomandy A, Murenzi G, Péré H, Del Pino M, Ortiz AP, Charnot-Katsikas A, Liu X, Chariyalertsak S, Strong C, Ong JJ, Yunihastuti E, Etienney I, Ferré VM, Zou H, Segondy M, Chinyowa S, Alberts CJ, Clifford GM
Lancet HIV 2021 Sep;8(9):e531-e543. Epub 2021 Jul 30 doi: 10.1016/S2352-3018(21)00108-9. PMID: 34339628Free PMC Article

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