Inmunodeficiencias combinadas

. Defectos de inmunidad adaptativa .

Panel Inmunodeficiencias combinadas (IDC) [37 genes]

Las inmunodeficiencias combinadas (IDC) son un grupo de enfermedades raras y congénitas, que se caracterizan por una respuesta inmune críticamente comprometida, aunque no tan severa como en la inmunodeficiencia combinada grave (IDCG). Las IDC están causadas por defectos genéticos que provocan una disminución del número de linfocitos T o una disfunción de los mismos; esto puede venir acompañado de defectos en los linfocitos B.

Características clínicas

Infecciones (viral, fúngica, bacteriana)
Autoinmunidad
Autoinflamación
Características sindrómicas
Inicio: infancia, niñez

Prevalencia

1 : 75.000 – 1:100.000

Beneficios y manejo

Diagnóstico diferencial con IDCG
Consejo genético
Trasplante de células madre hematopoyéticas (TCMH)
Terapia génica
Evitar vacunas con cepas vivas

B2M, BCL10, BCL11B, CARD11, CARMIL2, CASP8, CD27, CD40, CD40LG, CD8A, CIITA, CTPS1, DOCK2, DOCK8, ICOS, IKBKB, IL21, IL21R, LAT, LCK, MAGT1, MALT1, MAP3K14, MSN, RELB, RFX5, RFXANK, RFXAP, RHOH, STK4, TAP1, TAP2, TAPBP, TFRC, TNFRSF4, UNC119, ZAP70

Panel incluido

Síndrome del linfocito desnudo - 13 genes

Fenotipos relacionados

Genes	Fenotipo	MIM	PDH
B2M	Immunodeficiency 43 (IMD43) \| Amyloidosis, familial visceral	241600 \| 105200	AR \| AD
BCL10	Immunodeficiency 37 (IMD37) \| Lymphoma, MALT, somatic	616098 \| 137245	AR \| SMu
BCL11B	Immunodeficiency 49 (IMD49)	617237	AD
CARD11	Immunodeficiency 11A \| Immunodeficiency 11B with atopic dermatitis \| B cell expansion with NFKB and T cell anergy	615206 \| 617638 \| 616452	AR \| AD
CARMIL2	Combined immunodeficiency (candidate gene)	-	AR
CASP8	Autoimmune lymphoproliferative syndrome, type IIB	607271	AR
CD27	Lymphoproliferative syndrome 2	615122	AR
CD40	Immunodeficiency with hyper-IgM, type 3 (HIGM3)	606843	AR
CD40LG	Immunodeficiency, X-linked, with hyper-IgM (HIGM1)	308230	XLR
CD8A	CD8 deficiency, familial	608957	AR
CIITA	Bare lymphocyte syndrome, type II, complementation group A	209920	AR
CTPS1	Immunodeficiency 24 (IMD24)	615897	AR
DOCK2	Immunodeficiency 40 (IMD40)	616433	AR
DOCK8	Hyper-IgE recurrent infection syndrome, autosomal recessive	243700	AR
ICOS	Immunodeficiency, common variable, 1 (CVID1)	607594	AR
IKBKB	immunodeficiency 15 (IMD15)	615592	AR
IL21	Immunodeficiency, common variable, 11 (CVID11)	615767	AR \| Mu
IL21R	Immunodeficiency 56 (IMD56) \| IgE, elevated level of	615207 \| 147050	AR \| AD
LAT	Immunodeficiency 52 (IMD52)	617514	AR
LCK	Immunodeficiency 22 (IMD22)	615758	AR
MAGT1	Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia	300853	XLR
MALT1	Immunodeficiency 12 (IMD12)	615468	AR
MAP3K14	Combined immunodeficiency (candidate gene)	-	AR
MSN	Immunodeficiency 50 (IMD50)	300988	XLR
RELB	Immunodeficiency 53 (IMD53)	617585	AR
RFX5	Bare lymphocyte syndrome, type II, complementation group C \| Bare lymphocyte syndrome, type II, complementation group E	209920	AR
RFXANK	MHC class II deficiency, complementation group B	209920	AR
RFXAP	Bare lymphocyte syndrome, type II, complementation group D	209920	AR
RHOH	T-cell immunodeficiency with epidermodysplasia verruciformis (candidate gene)	-	AR
STK4	T cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations	614868	AR
TAP1	Bare lymphocyte syndrome, type I (BLSI)	604571	AR
TAP2	Bare lymphocyte syndrome, type I (BLSI)	604571	AR
TAPBP	Bare lymphocyte syndrome, type I (BLSI)	604571	AR
TFRC	Immunodeficiency 46 (IMD46)	616740	AR
TNFRSF4	Immunodeficiency 16 (IMD16)	615593	AR \| Mu
UNC119	Immunodeficiency 13 (IMD13)	615518	AD
ZAP70	Immunodeficiency 48 (IMD48) \| Autoimmune disease, multisystem, infantile-onset, 2	269840 \| 617006	AR

(*) MIM: código identificador de OMIM (Online Mendelian Inheritance in Man); PDH: patrón de herencia; AD: herencia autosómico dominante; AR: herencia autosómico recesiva; XL: herencia ligada al cromosoma X; XLR: herencia recesiva ligada al cromosoma X; XLD: herencia dominante ligada al cromosoma X; Mu: herencia multifactorial; SMu: mutación somática.

Referencias

Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS Phenotypic Classification for Inmunodeficiencias primarias. J Clin Immunol. 2018;38(1):129-143. doi:10.1007/s10875-017-0465-8
Immune deficiency foundation (IDF). Stem Cell and Gen Therapy. https://primaryimmune.org/treatment-information/stem-cell-and-gene-therapy. Accessed April 5, 2018.
National Human Genome Research Institute (NHGRI). Learning About Severe Combined Immunodeficiency (SCID). https://www.genome.gov/13014325/learning-about-severe-combined-immunodeficiency-scid/. Published 2014. Accessed April 5, 2018.
Lohmann K, Klein C. Next Generation Sequencing and the Future of Genetic Diagnosis. Neurotherapeutics. 2014;11(4):699-707. doi:10.1007/s13311-014-0288-8
Paul Szabolcs M-CH of P of U. Combined Immune Deficiency (CID) Syndromes. http://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/combined-immune-deficiency-syndromes. Accessed April 5, 2018.