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IL21-related infantile inflammatory bowel disease(CVID11)

MedGen UID:
1799211
Concept ID:
C5567788
Disease or Syndrome
Synonyms: Common variable immunodeficiency 11; IL21 DEFICIENCY
SNOMED CT: IL21-related infantile inflammatory bowel disease (1173999006); Interleukin 21 related infantile inflammatory bowel disease (1173999006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): IL21 (4q27)
 
Monarch Initiative: MONDO:0014338
OMIM®: 615767
Orphanet: ORPHA477661

Definition

A rare autosomal recessive primary immunodeficiency characterized by infancy onset of severe inflammatory bowel disease with life-threatening diarrhea and failure to thrive, oral aphthous ulcers, and recurrent severe upper and lower respiratory tract infections with finger clubbing. Laboratory examination reveals increased IgE and decreased IgG levels, as well as reduced numbers of circulating CD19+ B-cells including IgM+ naive and class-switched IgG memory B-cells, with a concomitant increase in transitional B-cells, while T-cell numbers and function are normal. [from SNOMEDCT_US]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Crohn disease
MedGen UID:
3664
Concept ID:
C0010346
Disease or Syndrome
A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.
Inflammation of the large intestine
MedGen UID:
662273
Concept ID:
C0578878
Disease or Syndrome
Inflammation, or an inflammatory state in the large intestine.
Mucoid diarrhea
MedGen UID:
1780149
Concept ID:
C3671554
Sign or Symptom
Passage of an increased number of stools containing mucus, a thick fluid substance secreted by mucous membranes.
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.
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
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 circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Aphthous stomatitis
MedGen UID:
20959
Concept ID:
C0038363
Disease or Syndrome
Oral aphthous ulcers typically present as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.

Professional guidelines

PubMed

Shaul E, Conrad MA, Dawany N, Patel T, Canavan MC, Baccarella A, Weinbrom S, Aleynick D, Sullivan KE, Kelsen JR
Front Immunol 2022;13:972114. Epub 2022 Sep 20 doi: 10.3389/fimmu.2022.972114. PMID: 36203564Free PMC Article
Ye Z, Hu W, Wu B, Zhang Y, Lei C, Williams I, Shouval DS, Kanegane H, Kim KM, de Ridder L, Shah N, Ling G, Yerushalmi B, Kotlarz D, Snapper S, Horn R, Klein C, Muise AM, Huang Y, Uhlig HH
J Pediatr Gastroenterol Nutr 2021 Feb 1;72(2):276-281. doi: 10.1097/MPG.0000000000002937. PMID: 32925557Free PMC Article
Vandenplas Y, Veereman-Wauters G, De Greef E, Peeters S, Casteels A, Mahler T, Devreker T, Hauser B
J Pediatr (Rio J) 2011 Jul-Aug;87(4):292-300. Epub 2011 Jul 8 doi: 10.2223/JPED.2103. PMID: 21769417

Recent clinical studies

Etiology

Duong QA, Pittet LF, Curtis N, Zimmermann P
J Infect 2022 Sep;85(3):213-300. Epub 2022 Jan 10 doi: 10.1016/j.jinf.2022.01.005. PMID: 35021114
Al-Shaibi AA, Abdel-Motal UM, Hubrack SZ, Bullock AN, Al-Marri AA, Agrebi N, Al-Subaiey AA, Ibrahim NA, Charles AK; COLORS in IBD-Qatar Study Group, Elawad M, Uhlig HH, Lo B
Cell Mol Gastroenterol Hepatol 2021;12(5):1809-1830. Epub 2021 Jul 6 doi: 10.1016/j.jcmgh.2021.07.001. PMID: 34237462Free PMC Article
Uhlig HH, Charbit-Henrion F, Kotlarz D, Shouval DS, Schwerd T, Strisciuglio C, de Ridder L, van Limbergen J, Macchi M, Snapper SB, Ruemmele FM, Wilson DC, Travis SPL, Griffiths AM, Turner D, Klein C, Muise AM, Russell RK; Paediatric IBD Porto group of ESPGHAN
J Pediatr Gastroenterol Nutr 2021 Mar 1;72(3):456-473. doi: 10.1097/MPG.0000000000003017. PMID: 33346580Free PMC Article
Gordon M, Biagioli E, Sorrenti M, Lingua C, Moja L, Banks SS, Ceratto S, Savino F
Cochrane Database Syst Rev 2018 Oct 10;10(10):CD011029. doi: 10.1002/14651858.CD011029.pub2. PMID: 30306546Free PMC Article
Gupta V, Garg R
Indian J Med Microbiol 2009 Jul-Sep;27(3):202-9. doi: 10.4103/0255-0857.53201. PMID: 19584499

Diagnosis

Shaul E, Conrad MA, Dawany N, Patel T, Canavan MC, Baccarella A, Weinbrom S, Aleynick D, Sullivan KE, Kelsen JR
Front Immunol 2022;13:972114. Epub 2022 Sep 20 doi: 10.3389/fimmu.2022.972114. PMID: 36203564Free PMC Article
Al-Shaibi AA, Abdel-Motal UM, Hubrack SZ, Bullock AN, Al-Marri AA, Agrebi N, Al-Subaiey AA, Ibrahim NA, Charles AK; COLORS in IBD-Qatar Study Group, Elawad M, Uhlig HH, Lo B
Cell Mol Gastroenterol Hepatol 2021;12(5):1809-1830. Epub 2021 Jul 6 doi: 10.1016/j.jcmgh.2021.07.001. PMID: 34237462Free PMC Article
Uhlig HH, Charbit-Henrion F, Kotlarz D, Shouval DS, Schwerd T, Strisciuglio C, de Ridder L, van Limbergen J, Macchi M, Snapper SB, Ruemmele FM, Wilson DC, Travis SPL, Griffiths AM, Turner D, Klein C, Muise AM, Russell RK; Paediatric IBD Porto group of ESPGHAN
J Pediatr Gastroenterol Nutr 2021 Mar 1;72(3):456-473. doi: 10.1097/MPG.0000000000003017. PMID: 33346580Free PMC Article
Ye Z, Hu W, Wu B, Zhang Y, Lei C, Williams I, Shouval DS, Kanegane H, Kim KM, de Ridder L, Shah N, Ling G, Yerushalmi B, Kotlarz D, Snapper S, Horn R, Klein C, Muise AM, Huang Y, Uhlig HH
J Pediatr Gastroenterol Nutr 2021 Feb 1;72(2):276-281. doi: 10.1097/MPG.0000000000002937. PMID: 32925557Free PMC Article
Thiagarajah JR, Kamin DS, Acra S, Goldsmith JD, Roland JT, Lencer WI, Muise AM, Goldenring JR, Avitzur Y, Martín MG; PediCODE Consortium
Gastroenterology 2018 Jun;154(8):2045-2059.e6. Epub 2018 Apr 12 doi: 10.1053/j.gastro.2018.03.067. PMID: 29654747Free PMC Article

Therapy

Dargenio VN, Castellaneta S, Panico S, Papagni ME, Dargenio C, Schettini F, Francavilla R, Cristofori F
Minerva Pediatr (Torino) 2022 Dec;74(6):703-723. Epub 2022 Oct 31 doi: 10.23736/S2724-5276.22.07031-8. PMID: 36315413
Shaul E, Conrad MA, Dawany N, Patel T, Canavan MC, Baccarella A, Weinbrom S, Aleynick D, Sullivan KE, Kelsen JR
Front Immunol 2022;13:972114. Epub 2022 Sep 20 doi: 10.3389/fimmu.2022.972114. PMID: 36203564Free PMC Article
Duong QA, Pittet LF, Curtis N, Zimmermann P
J Infect 2022 Sep;85(3):213-300. Epub 2022 Jan 10 doi: 10.1016/j.jinf.2022.01.005. PMID: 35021114
Gordon M, Biagioli E, Sorrenti M, Lingua C, Moja L, Banks SS, Ceratto S, Savino F
Cochrane Database Syst Rev 2018 Oct 10;10(10):CD011029. doi: 10.1002/14651858.CD011029.pub2. PMID: 30306546Free PMC Article
Gupta V, Garg R
Indian J Med Microbiol 2009 Jul-Sep;27(3):202-9. doi: 10.4103/0255-0857.53201. PMID: 19584499

Prognosis

Collen LV, Kim DY, Field M, Okoroafor I, Saccocia G, Whitcomb SD, Green J, Dong MD, Barends J, Carey B, Weatherly ME; Regeneron Genetics centre, Rockowitz S, Sliz P, Liu E, Eran A, Grushkin-Lerner L, Bousvaros A, Muise AM, Klein C, Mitsialis V, Ouahed J, Snapper SB
J Crohns Colitis 2022 Sep 8;16(9):1380-1396. doi: 10.1093/ecco-jcc/jjac045. PMID: 35366317Free PMC Article
Ye Z, Hu W, Wu B, Zhang Y, Lei C, Williams I, Shouval DS, Kanegane H, Kim KM, de Ridder L, Shah N, Ling G, Yerushalmi B, Kotlarz D, Snapper S, Horn R, Klein C, Muise AM, Huang Y, Uhlig HH
J Pediatr Gastroenterol Nutr 2021 Feb 1;72(2):276-281. doi: 10.1097/MPG.0000000000002937. PMID: 32925557Free PMC Article
Kudo T, Fujii T, Maisawa SI, Sasaki M, Uchida K, Ida S, Kagimoto S, Yoden A, Shimizu T
Digestion 2021;102(3):368-376. Epub 2020 May 18 doi: 10.1159/000507570. PMID: 32422640
Alvisi P, Dipasquale V, Barabino A, Martellossi S, Miele E, Lionetti P, Lombardi G, Cucchiara S, Torre G, Romano C
Expert Rev Gastroenterol Hepatol 2019 Oct;13(10):957-961. Epub 2019 Sep 6 doi: 10.1080/17474124.2019.1663173. PMID: 31490707
Moran CJ, Klein C, Muise AM, Snapper SB
Inflamm Bowel Dis 2015 May;21(5):1166-75. doi: 10.1097/MIB.0000000000000329. PMID: 25895007Free PMC Article

Clinical prediction guides

Shaul E, Conrad MA, Dawany N, Patel T, Canavan MC, Baccarella A, Weinbrom S, Aleynick D, Sullivan KE, Kelsen JR
Front Immunol 2022;13:972114. Epub 2022 Sep 20 doi: 10.3389/fimmu.2022.972114. PMID: 36203564Free PMC Article
Duong QA, Pittet LF, Curtis N, Zimmermann P
J Infect 2022 Sep;85(3):213-300. Epub 2022 Jan 10 doi: 10.1016/j.jinf.2022.01.005. PMID: 35021114
Ye Z, Hu W, Wu B, Zhang Y, Lei C, Williams I, Shouval DS, Kanegane H, Kim KM, de Ridder L, Shah N, Ling G, Yerushalmi B, Kotlarz D, Snapper S, Horn R, Klein C, Muise AM, Huang Y, Uhlig HH
J Pediatr Gastroenterol Nutr 2021 Feb 1;72(2):276-281. doi: 10.1097/MPG.0000000000002937. PMID: 32925557Free PMC Article
Cruchet S, Furnes R, Maruy A, Hebel E, Palacios J, Medina F, Ramirez N, Orsi M, Rondon L, Sdepanian V, Xóchihua L, Ybarra M, Zablah RA
Paediatr Drugs 2015 Jun;17(3):199-216. doi: 10.1007/s40272-015-0124-6. PMID: 25799959Free PMC Article
Denson LA
Curr Gastroenterol Rep 2012 Jun;14(3):275-81. doi: 10.1007/s11894-012-0258-4. PMID: 22422506Free PMC Article

Recent systematic reviews

Duong QA, Pittet LF, Curtis N, Zimmermann P
J Infect 2022 Sep;85(3):213-300. Epub 2022 Jan 10 doi: 10.1016/j.jinf.2022.01.005. PMID: 35021114
Kamphorst K, Van Daele E, Vlieger AM, Daams JG, Knol J, van Elburg RM
BMJ Paediatr Open 2021;5(1):e001028. Epub 2021 Mar 3 doi: 10.1136/bmjpo-2021-001028. PMID: 33748435Free PMC Article
Uhlig HH, Charbit-Henrion F, Kotlarz D, Shouval DS, Schwerd T, Strisciuglio C, de Ridder L, van Limbergen J, Macchi M, Snapper SB, Ruemmele FM, Wilson DC, Travis SPL, Griffiths AM, Turner D, Klein C, Muise AM, Russell RK; Paediatric IBD Porto group of ESPGHAN
J Pediatr Gastroenterol Nutr 2021 Mar 1;72(3):456-473. doi: 10.1097/MPG.0000000000003017. PMID: 33346580Free PMC Article
Gubatan J, Nielsen OH, Levitte S, Juhl CB, Maxwell C, Streett SE, Habtezion A
Am J Gastroenterol 2021 Feb 1;116(2):243-253. doi: 10.14309/ajg.0000000000000910. PMID: 33110017Free PMC Article
Gordon M, Biagioli E, Sorrenti M, Lingua C, Moja L, Banks SS, Ceratto S, Savino F
Cochrane Database Syst Rev 2018 Oct 10;10(10):CD011029. doi: 10.1002/14651858.CD011029.pub2. PMID: 30306546Free PMC Article

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