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Autoimmune lymphoproliferative syndrome type 2B(ALPS2B)

MedGen UID:
339548
Concept ID:
C1846545
Disease or Syndrome
Synonyms: AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE IIB; Caspase-8 deficiency
SNOMED CT: Autoimmune lymphoproliferative syndrome with recurrent viral infection (722290008); Caspase 8 deficiency syndrome (722290008)
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): CASP8 (2q33.1)
 
Monarch Initiative: MONDO:0011804
OMIM®: 607271
Orphanet: ORPHA275517

Definition

Caspase 8 deficiency is a syndrome of lymphadenopathy and splenomegaly, marginal elevation of 'double-negative T cells' (DNT; T-cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective T-, B-, and natural killer (NK)-cell activation, with recurrent bacterial and viral infections (summary by Madkaikar et al., 2011). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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.
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.
Recurrent sinopulmonary infections
MedGen UID:
339549
Concept ID:
C1846546
Finding
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Decreased circulating IgA level
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
Decreased CD4:CD8 ratio
MedGen UID:
163125
Concept ID:
C0853905
Finding
An abnormal reduction of the relative proportion of CD4+ to CD8+ T cells.
Decreased T cell activation
MedGen UID:
339550
Concept ID:
C1846550
Finding
Decreased or impaired activation of T cells in response to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
Defective B cell activation
MedGen UID:
375916
Concept ID:
C1846551
Finding
A reduced ability of a B cell to become activated, i.e., the change in morphology and behavior of
Recurrent herpes
MedGen UID:
870750
Concept ID:
C4025207
Finding
Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus.
Complete or near-complete absence of specific antibody response to unconjugated pneumococcus vaccine
MedGen UID:
1704477
Concept ID:
C5139463
Finding
The inability to synthesize postvaccination antibodies against a pneumococcus 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.
Reduced CD95-induced lymphocyte apoptosis
MedGen UID:
1780105
Concept ID:
C5539476
Finding
Reduced amount of programmed cell death in peripheral blood lymphocytes following exposure to CD95 (APO-1/Fas), which is a member of the death receptor family, a subfamily of the TNF-R superfamily. Crosslinking of CD95 with its natural ligand CD95L (CD178) or with agonistic antibodies such as anti-APO-1 induces apoptosis in sensitive cells.

Professional guidelines

PubMed

Zhao EJ, Cheng CV, Mattman A, Chen LYC
Lancet Haematol 2021 May;8(5):e365-e375. doi: 10.1016/S2352-3026(21)00056-9. PMID: 33894171
Lee AS, Scofield RH, Hammitt KM, Gupta N, Thomas DE, Moua T, Ussavarungsi K, St Clair EW, Meehan R, Dunleavy K, Makara M, Carsons SE, Carteron NL; Consensus Expert Panel (CEP) Members
Chest 2021 Feb;159(2):683-698. Epub 2020 Oct 16 doi: 10.1016/j.chest.2020.10.011. PMID: 33075377Free PMC Article
Jonsson R, Brokstad KA, Jonsson MV, Delaleu N, Skarstein K
Eur J Oral Sci 2018 Oct;126 Suppl 1(Suppl Suppl 1):37-48. doi: 10.1111/eos.12536. PMID: 30178554Free PMC Article

Recent clinical studies

Etiology

Luppi F, Sebastiani M, Sverzellati N, Cavazza A, Salvarani C, Manfredi A
Eur Respir Rev 2020 Sep 30;29(157) Epub 2020 Aug 18 doi: 10.1183/16000617.0021-2020. PMID: 32817113Free PMC Article
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article
Matson DR, Yang DT
Arch Pathol Lab Med 2020 Feb;144(2):245-251. Epub 2019 Apr 8 doi: 10.5858/arpa.2018-0190-RS. PMID: 30958694Free PMC Article
Jonsson R, Brokstad KA, Jonsson MV, Delaleu N, Skarstein K
Eur J Oral Sci 2018 Oct;126 Suppl 1(Suppl Suppl 1):37-48. doi: 10.1111/eos.12536. PMID: 30178554Free PMC Article
Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T
Allergol Int 2018 Jan;67(1):43-54. Epub 2017 Jul 3 doi: 10.1016/j.alit.2017.06.003. PMID: 28684198

Diagnosis

Lambert MP
Expert Rev Clin Immunol 2021 Nov;17(11):1163-1173. Epub 2021 Sep 17 doi: 10.1080/1744666X.2021.1978842. PMID: 34503378
Luppi F, Sebastiani M, Sverzellati N, Cavazza A, Salvarani C, Manfredi A
Eur Respir Rev 2020 Sep 30;29(157) Epub 2020 Aug 18 doi: 10.1183/16000617.0021-2020. PMID: 32817113Free PMC Article
Matson DR, Yang DT
Arch Pathol Lab Med 2020 Feb;144(2):245-251. Epub 2019 Apr 8 doi: 10.5858/arpa.2018-0190-RS. PMID: 30958694Free PMC Article
Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T
Allergol Int 2018 Jan;67(1):43-54. Epub 2017 Jul 3 doi: 10.1016/j.alit.2017.06.003. PMID: 28684198
Gehrs BC, Friedberg RC
Am J Hematol 2002 Apr;69(4):258-71. doi: 10.1002/ajh.10062. PMID: 11921020

Therapy

Paskiewicz A, Niu J, Chang C
Autoimmun Rev 2023 Nov;22(11):103442. Epub 2023 Sep 6 doi: 10.1016/j.autrev.2023.103442. PMID: 37683818
Sharma K, Tolaymat S, Yu H, Elkhooly M, Jaiswal S, Jena A, Kakara M, Sriwastava S
J Neurol Sci 2022 Dec 15;443:120459. Epub 2022 Oct 14 doi: 10.1016/j.jns.2022.120459. PMID: 36283150
Zhao EJ, Cheng CV, Mattman A, Chen LYC
Lancet Haematol 2021 May;8(5):e365-e375. doi: 10.1016/S2352-3026(21)00056-9. PMID: 33894171
Luppi F, Sebastiani M, Sverzellati N, Cavazza A, Salvarani C, Manfredi A
Eur Respir Rev 2020 Sep 30;29(157) Epub 2020 Aug 18 doi: 10.1183/16000617.0021-2020. PMID: 32817113Free PMC Article
Silva F, Pinto C, Barbosa A, Borges T, Dias C, Almeida J
J Autoimmun 2019 Dec;105:102313. Epub 2019 Aug 2 doi: 10.1016/j.jaut.2019.102313. PMID: 31383568

Prognosis

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Costagliola G, Consolini R
Clin Exp Immunol 2021 Sep;205(3):288-305. Epub 2021 Jun 20 doi: 10.1111/cei.13620. PMID: 34008169Free PMC Article
Neven Q, Boulanger C, Bruwier A, de Ville de Goyet M, Meyts I, Moens L, Van Damme A, Brichard B
J Clin Immunol 2021 Jan;41(1):51-58. Epub 2020 Oct 4 doi: 10.1007/s10875-020-00883-7. PMID: 33011939
Luppi F, Sebastiani M, Sverzellati N, Cavazza A, Salvarani C, Manfredi A
Eur Respir Rev 2020 Sep 30;29(157) Epub 2020 Aug 18 doi: 10.1183/16000617.0021-2020. PMID: 32817113Free PMC Article
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article

Clinical prediction guides

Maccari ME, Wolkewitz M, Schwab C, Lorenzini T, Leiding JW, Aladjdi N, Abolhassani H, Abou-Chahla W, Aiuti A, Azarnoush S, Baris S, Barlogis V, Barzaghi F, Baumann U, Bloomfield M, Bohynikova N, Bodet D, Boutboul D, Bucciol G, Buckland MS, Burns SO, Cancrini C, Cathébras P, Cavazzana M, Cheminant M, Chinello M, Ciznar P, Coulter TI, D'Aveni M, Ekwall O, Eric Z, Eren E, Fasth A, Frange P, Fournier B, Garcia-Prat M, Gardembas M, Geier C, Ghosh S, Goda V, Hammarström L, Hauck F, Heeg M, Heropolitanska-Pliszka E, Hilfanova A, Jolles S, Karakoc-Aydiner E, Kindle GR, Kiykim A, Klemann C, Koletsi P, Koltan S, Kondratenko I, Körholz J, Krüger R, Jeziorski E, Levy R, Le Guenno G, Lefevre G, Lougaris V, Marzollo A, Mahlaoui N, Malphettes M, Meinhardt A, Merlin E, Meyts I, Milota T, Moreira F, Moshous D, Mukhina A, Neth O, Neubert J, Neven B, Nieters A, Nove-Josserand R, Oksenhendler E, Ozen A, Olbrich P, Perlat A, Pac M, Schmid JP, Pacillo L, Parra-Martinez A, Paschenko O, Pellier I, Sefer AP, Plebani A, Plantaz D, Prader S, Raffray L, Ritterbusch H, Riviere JG, Rivalta B, Rusch S, Sakovich I, Savic S, Scheible R, Schleinitz N, Schuetz C, Schulz A, Sediva A, Semeraro M, Sharapova SO, Shcherbina A, Slatter MA, Sogkas G, Soler-Palacin P, Speckmann C, Stephan JL, Suarez F, Tommasini A, Trück J, Uhlmann A, van Aerde KJ, van Montfrans J, von Bernuth H, Warnatz K, Williams T, Worth AJJ, Ip W, Picard C, Catherinot E, Nademi Z, Grimbacher B, Forbes Satter LR, Kracker S, Chandra A, Condliffe AM, Ehl S; European Society for Immunodeficiencies Registry Working Party
J Allergy Clin Immunol 2023 Oct;152(4):984-996.e10. Epub 2023 Jun 28 doi: 10.1016/j.jaci.2023.06.015. PMID: 37390899
Maccari ME, Schneider P, Smulski CR, Meinhardt A, Pinto F, Gonzalez-Granado LI, Schuetz C, Sica MP, Gross M, Fuchs I, Kury P, Heeg M, Vocat T, Willen L, Thomas C, Hühn R, Magerus A, Lorenz M, Schwarz K, Rieux-Laucat F, Ehl S, Rensing-Ehl A
J Allergy Clin Immunol 2023 May;151(5):1391-1401.e7. Epub 2023 Jan 5 doi: 10.1016/j.jaci.2022.11.028. PMID: 36621650
Gámez-Díaz L, Grimbacher B
Biomed J 2021 Aug;44(4):400-411. Epub 2021 Apr 19 doi: 10.1016/j.bj.2021.04.005. PMID: 34384744Free PMC Article
Costagliola G, Consolini R
Clin Exp Immunol 2021 Sep;205(3):288-305. Epub 2021 Jun 20 doi: 10.1111/cei.13620. PMID: 34008169Free PMC Article
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article

Recent systematic reviews

Saglam A, Singh K, Gollapudi S, Kumar J, Brar N, Butzmann A, Warnke R, Ohgami RS
Int J Lab Hematol 2022 Aug;44(4):700-711. Epub 2022 May 16 doi: 10.1111/ijlh.13873. PMID: 35577551
López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Hafezi N, Zaki-Dizaji M, Nirouei M, Asadi G, Sharifinejad N, Jamee M, Erfan Rasouli S, Hamedifar H, Sabzevari A, Chavoshzadeh Z, Yazdani R, Abolhassani H, Aghamohammadi A, Azizi G
Pediatr Allergy Immunol 2021 Oct;32(7):1519-1532. Epub 2021 May 27 doi: 10.1111/pai.13535. PMID: 33963613
Ramos-Casals M, Brito-Zerón P, Seror R, Bootsma H, Bowman SJ, Dörner T, Gottenberg JE, Mariette X, Theander E, Bombardieri S, De Vita S, Mandl T, Ng WF, Kruize A, Tzioufas A, Vitali C; EULAR Sjögren Syndrome Task Force
Rheumatology (Oxford) 2015 Dec;54(12):2230-8. Epub 2015 Jul 31 doi: 10.1093/rheumatology/kev200. PMID: 26231345Free PMC Article
Liang Y, Zhang L, Gao J, Hu D, Ai Y
PLoS One 2012;7(5):e36698. Epub 2012 May 30 doi: 10.1371/journal.pone.0036698. PMID: 22666325Free PMC Article

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