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Immunodeficiency 62(IMD62)

MedGen UID:
1673905
Concept ID:
C5193109
Disease or Syndrome
Synonyms: IMD62; IMMUNODEFICIENCY 62
 
Gene (location): ARHGEF1 (19q13.2)
 
Monarch Initiative: MONDO:0032763
OMIM®: 618459

Definition

Immunodeficiency-62 (IMD62) is an autosomal recessive primary immunologic disorder clinically characterized by onset of recurrent upper and lower respiratory infections late in the first decade of life. Patients may also have increased viral susceptibility to varicella zoster virus (VZV) or herpes simplex virus (HSV). Laboratory studies show impaired antibody response to vaccination, low levels of circulating memory B cells, and almost undetectable antibodies. There is also evidence of secondary T-cell dysfunction. The disorder may result from disturbed actin cytoskeleton dynamics causing impaired lymphocyte migration (summary by Bouafia et al., 2019). [from OMIM]

Clinical features

From HPO
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 upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
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.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Varicella, severe recurrent
MedGen UID:
322202
Concept ID:
C1833487
Disease or Syndrome
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Recurrent herpes
MedGen UID:
870750
Concept ID:
C4025207
Finding
Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus.
Decreased proportion of memory B cells
MedGen UID:
893145
Concept ID:
C4072913
Finding
A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).
Increased proportion of transitional B cells
MedGen UID:
892766
Concept ID:
C4072920
Finding
An elevation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.
Reduced isohemagglutinin level
MedGen UID:
1700218
Concept ID:
C5139157
Finding
Level of isohemagglutinin reduced below expected concentration. An isohemagglutinin refers to the naturally occurring antibodies in the ABO blood group system (i.e., anti-A in a group B person, anti-B in a group A person, and anti-A, anti-B, and anti-A,B in a group O person).
Complete or near-complete absence of specific antibody response to tetanus vaccine
MedGen UID:
1687415
Concept ID:
C5139458
Finding
The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.

Professional guidelines

PubMed

Kang R, Li J, Chen H, Tang Z, Pan SW, Luo L, Zhu Q, Lan G, Liang S, Lu H, Zhu J, Feng Y, Liao L, Xing H, Shao Y, Ruan Y, Shen Z
AIDS 2021 May 1;35(6):947-955. doi: 10.1097/QAD.0000000000002812. PMID: 33443369
Wu X, Shen Y
Mycoses 2019 Oct;62(10):874-882. Epub 2019 Aug 18 doi: 10.1111/myc.12977. PMID: 31365770
Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom DM, Lucena JM, Seidl M, Schmitt-Graeff A, Reiser V, Emmerich F, Frede N, Bulashevska A, Salzer U, Schubert D, Hayakawa S, Okada S, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Sumnik Z, Sediva A, Slatter M, Arkwright PD, Cant A, Lorenz HM, Giese T, Lougaris V, Plebani A, Price C, Sullivan KE, Moutschen M, Litzman J, Freiberger T, van de Veerdonk FL, Recher M, Albert MH, Hauck F, Seneviratne S, Pachlopnik Schmid J, Kolios A, Unglik G, Klemann C, Speckmann C, Ehl S, Leichtner A, Blumberg R, Franke A, Snapper S, Zeissig S, Cunningham-Rundles C, Giulino-Roth L, Elemento O, Dückers G, Niehues T, Fronkova E, Kanderová V, Platt CD, Chou J, Chatila TA, Geha R, McDermott E, Bunn S, Kurzai M, Schulz A, Alsina L, Casals F, Deyà-Martinez A, Hambleton S, Kanegane H, Taskén K, Neth O, Grimbacher B
J Allergy Clin Immunol 2018 Dec;142(6):1932-1946. Epub 2018 May 4 doi: 10.1016/j.jaci.2018.02.055. PMID: 29729943Free PMC Article

Recent clinical studies

Etiology

Leiding JW, Vogel TP, Santarlas VGJ, Mhaskar R, Smith MR, Carisey A, Vargas-Hernández A, Silva-Carmona M, Heeg M, Rensing-Ehl A, Neven B, Hadjadj J, Hambleton S, Ronan Leahy T, Meesilpavikai K, Cunningham-Rundles C, Dutmer CM, Sharapova SO, Taskinen M, Chua I, Hague R, Klemann C, Kostyuchenko L, Morio T, Thatayatikom A, Ozen A, Scherbina A, Bauer CS, Flanagan SE, Gambineri E, Giovannini-Chami L, Heimall J, Sullivan KE, Allenspach E, Romberg N, Deane SG, Prince BT, Rose MJ, Bohnsack J, Mousallem T, Jesudas R, Santos Vilela MMD, O'Sullivan M, Pachlopnik Schmid J, Průhová Š, Klocperk A, Rees M, Su H, Bahna S, Baris S, Bartnikas LM, Chang Berger A, Briggs TA, Brothers S, Bundy V, Chan AY, Chandrakasan S, Christiansen M, Cole T, Cook MC, Desai MM, Fischer U, Fulcher DA, Gallo S, Gauthier A, Gennery AR, Gonçalo Marques J, Gottrand F, Grimbacher B, Grunebaum E, Haapaniemi E, Hämäläinen S, Heiskanen K, Heiskanen-Kosma T, Hoffman HM, Gonzalez-Granado LI, Guerrerio AL, Kainulainen L, Kumar A, Lawrence MG, Levin C, Martelius T, Neth O, Olbrich P, Palma A, Patel NC, Pozos T, Preece K, Lugo Reyes SO, Russell MA, Schejter Y, Seroogy C, Sinclair J, Skevofilax E, Suan D, Suez D, Szabolcs P, Velasco H, Warnatz K, Walkovich K, Worth A; STAT3 GOF Working Group members, Seppänen MRJ, Torgerson TR, Sogkas G, Ehl S, Tangye SG, Cooper MA, Milner JD, Forbes Satter LR
J Allergy Clin Immunol 2023 Apr;151(4):1081-1095. Epub 2022 Oct 11 doi: 10.1016/j.jaci.2022.09.002. PMID: 36228738Free PMC Article
Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921
Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595
Zaki-Dizaji M, Akrami SM, Azizi G, Abolhassani H, Aghamohammadi A
Inflamm Res 2018 Jul;67(7):559-570. Epub 2018 Mar 26 doi: 10.1007/s00011-018-1142-y. PMID: 29582093
Rühl H, Bein G, Sachs UJ
Transfus Med Rev 2009 Jan;23(1):62-71. doi: 10.1016/j.tmrv.2008.09.006. PMID: 19056035

Diagnosis

Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS, Corral Herrera EA, Crabtree-Ramirez B, Blanco JL, Girometti N, Mazzotta V, Hazra A, Silva M, Montenegro-Idrogo JJ, Gebo K, Ghosn J, Peña Vázquez MF, Matos Prado E, Unigwe U, Villar-García J, Wald-Dickler N, Zucker J, Paredes R, Calmy A, Waters L, Galvan-Casas C, Walmsley S, Orkin CM; SHARE-NET writing group
Lancet 2023 Mar 18;401(10380):939-949. Epub 2023 Feb 21 doi: 10.1016/S0140-6736(23)00273-8. PMID: 36828001
Leiding JW, Vogel TP, Santarlas VGJ, Mhaskar R, Smith MR, Carisey A, Vargas-Hernández A, Silva-Carmona M, Heeg M, Rensing-Ehl A, Neven B, Hadjadj J, Hambleton S, Ronan Leahy T, Meesilpavikai K, Cunningham-Rundles C, Dutmer CM, Sharapova SO, Taskinen M, Chua I, Hague R, Klemann C, Kostyuchenko L, Morio T, Thatayatikom A, Ozen A, Scherbina A, Bauer CS, Flanagan SE, Gambineri E, Giovannini-Chami L, Heimall J, Sullivan KE, Allenspach E, Romberg N, Deane SG, Prince BT, Rose MJ, Bohnsack J, Mousallem T, Jesudas R, Santos Vilela MMD, O'Sullivan M, Pachlopnik Schmid J, Průhová Š, Klocperk A, Rees M, Su H, Bahna S, Baris S, Bartnikas LM, Chang Berger A, Briggs TA, Brothers S, Bundy V, Chan AY, Chandrakasan S, Christiansen M, Cole T, Cook MC, Desai MM, Fischer U, Fulcher DA, Gallo S, Gauthier A, Gennery AR, Gonçalo Marques J, Gottrand F, Grimbacher B, Grunebaum E, Haapaniemi E, Hämäläinen S, Heiskanen K, Heiskanen-Kosma T, Hoffman HM, Gonzalez-Granado LI, Guerrerio AL, Kainulainen L, Kumar A, Lawrence MG, Levin C, Martelius T, Neth O, Olbrich P, Palma A, Patel NC, Pozos T, Preece K, Lugo Reyes SO, Russell MA, Schejter Y, Seroogy C, Sinclair J, Skevofilax E, Suan D, Suez D, Szabolcs P, Velasco H, Warnatz K, Walkovich K, Worth A; STAT3 GOF Working Group members, Seppänen MRJ, Torgerson TR, Sogkas G, Ehl S, Tangye SG, Cooper MA, Milner JD, Forbes Satter LR
J Allergy Clin Immunol 2023 Apr;151(4):1081-1095. Epub 2022 Oct 11 doi: 10.1016/j.jaci.2022.09.002. PMID: 36228738Free PMC Article
Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921
Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595
Hernandez-Trujillo VP
Immunol Allergy Clin North Am 2015 Nov;35(4):625-36. Epub 2015 Sep 4 doi: 10.1016/j.iac.2015.07.005. PMID: 26454310

Therapy

Peer N, Nguyen KA, Hill J, Sumner AE, Cikomola JC, Nachega JB, Kengne AP
J Int AIDS Soc 2023 Mar;26(3):e26059. doi: 10.1002/jia2.26059. PMID: 36924213Free PMC Article
Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921
Bomfim IGO, Santos SS, Napoleão AA
AIDS Patient Care STDS 2022 Jul;36(7):278-284. doi: 10.1089/apc.2022.0056. PMID: 35797650
Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258
Anglemyer A, Rutherford GW, Horvath T, Baggaley RC, Egger M, Siegfried N
Cochrane Database Syst Rev 2013 Apr 30;4(4):CD009153. doi: 10.1002/14651858.CD009153.pub3. PMID: 23633367Free PMC Article

Prognosis

Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921
Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595
Guo H, Liu J, Pu L, Hao J, Yin N, Liu Y, Xiong H, Li A
BMC Nephrol 2020 Mar 11;21(1):95. doi: 10.1186/s12882-020-01754-4. PMID: 32160882Free PMC Article
Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL
Circulation 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369. PMID: 29967196Free PMC Article
Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

Clinical prediction guides

Ben Khaled M, Merdassi A, Rekaya S, Fraj IB, Lamouchi T, Zaiter I, Kouki R, Bejaoui M, Mellouli F, Ouederni M
Clin Rheumatol 2023 Nov;42(11):3123-3129. Epub 2023 Jul 28 doi: 10.1007/s10067-023-06722-5. PMID: 37505303
Leiding JW, Vogel TP, Santarlas VGJ, Mhaskar R, Smith MR, Carisey A, Vargas-Hernández A, Silva-Carmona M, Heeg M, Rensing-Ehl A, Neven B, Hadjadj J, Hambleton S, Ronan Leahy T, Meesilpavikai K, Cunningham-Rundles C, Dutmer CM, Sharapova SO, Taskinen M, Chua I, Hague R, Klemann C, Kostyuchenko L, Morio T, Thatayatikom A, Ozen A, Scherbina A, Bauer CS, Flanagan SE, Gambineri E, Giovannini-Chami L, Heimall J, Sullivan KE, Allenspach E, Romberg N, Deane SG, Prince BT, Rose MJ, Bohnsack J, Mousallem T, Jesudas R, Santos Vilela MMD, O'Sullivan M, Pachlopnik Schmid J, Průhová Š, Klocperk A, Rees M, Su H, Bahna S, Baris S, Bartnikas LM, Chang Berger A, Briggs TA, Brothers S, Bundy V, Chan AY, Chandrakasan S, Christiansen M, Cole T, Cook MC, Desai MM, Fischer U, Fulcher DA, Gallo S, Gauthier A, Gennery AR, Gonçalo Marques J, Gottrand F, Grimbacher B, Grunebaum E, Haapaniemi E, Hämäläinen S, Heiskanen K, Heiskanen-Kosma T, Hoffman HM, Gonzalez-Granado LI, Guerrerio AL, Kainulainen L, Kumar A, Lawrence MG, Levin C, Martelius T, Neth O, Olbrich P, Palma A, Patel NC, Pozos T, Preece K, Lugo Reyes SO, Russell MA, Schejter Y, Seroogy C, Sinclair J, Skevofilax E, Suan D, Suez D, Szabolcs P, Velasco H, Warnatz K, Walkovich K, Worth A; STAT3 GOF Working Group members, Seppänen MRJ, Torgerson TR, Sogkas G, Ehl S, Tangye SG, Cooper MA, Milner JD, Forbes Satter LR
J Allergy Clin Immunol 2023 Apr;151(4):1081-1095. Epub 2022 Oct 11 doi: 10.1016/j.jaci.2022.09.002. PMID: 36228738Free PMC Article
Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921
Jewell PD, Abraham A, Schmidt V, Buell KG, Bustos JA, Garcia HH, Dixon MA, Walker M, Ngowi BJ, Basáñez MG, Winkler AS
Trop Med Int Health 2021 Oct;26(10):1140-1152. Epub 2021 Aug 23 doi: 10.1111/tmi.13652. PMID: 34228854
Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

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
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
Sun Z, Gu Q, Dai Y, Zou H, Agins B, Chen Q, Li P, Shen J, Yang Y, Jiang H
J Int AIDS Soc 2022 Mar;25(3):e25883. doi: 10.1002/jia2.25883. PMID: 35255193Free PMC Article
Senécal J, Smyth E, Del Corpo O, Hsu JM, Amar-Zifkin A, Bergeron A, Cheng MP, Butler-Laporte G, McDonald EG, Lee TC
Clin Microbiol Infect 2022 Jan;28(1):23-30. Epub 2021 Aug 28 doi: 10.1016/j.cmi.2021.08.017. PMID: 34464734
Mirbeyk M, Saghazadeh A, Rezaei N
Arch Gynecol Obstet 2021 Jul;304(1):5-38. Epub 2021 Apr 2 doi: 10.1007/s00404-021-06049-z. PMID: 33797605Free PMC Article

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