Inmunodeficiencias combinadas graves

. Defectos de inmunidad adaptativa .

Panel Inmunodeficiencias combinadas graves (IDCG) [19 genes]

La inmunodeficiencias combinadas graves (IDCG) representan un grupo de inmunodeficiencias primarias (IDP) raras, y potencialmente letales, caracterizadas por la falta de linfocitos T periféricos funcionales, que se clasifican como IDCG (T-B+) o IDCG (T-B-) en función de la presencia o ausencia de linfocitos B funcionales, respectivamente. En ambos casos, estos defectos pueden estar acompañados de ausencia de células NK funcionales. La IDCG es causada por alteraciones en distintos genes implicados en la maduración y la función del linaje de células T, células B y células NK.

Características clínicas

Infecciones severas (viral, fúngica, bacteriana) potencialmente letales
Diarrea
Retraso del crecimiento
Autoinmunidad
Inicio: neonatal, infancia

Prevalencia

1-9:1.000.000
40-100 neonatos/año en EEUU

Beneficios y manejo

Diagnóstico diferencial con SLD o agammaglobulinemia
Consejo genético
Trasplante de células madre hematopoyéticas (TCMH)
Terapia génica

ADA, AK2, CD247, CD3D, CD3E, CD3G, CORO1A, DCLRE1C, FOXN1, IL2RA, IL2RG, IL7R, JAK3, LIG4, NHEJ1, PRKDC, PTPRC, RAG1, RAG2

Paneles incluidos

Inmunodeficiencia combinada (T-B+) grave - 11 genes

Inmunodeficiencia combinada (T-B-) grave - 8 genes

Fenotipos relacionados

Genes	Fenotipo	MIM	PDH
ADA	Severe combined immunodeficiency due to ADA deficiency	102700	AR
AK2	Reticular dysgenesis	267500	AR
CD247	Immunodeficiency 25 (IMD25)	610163	AR
CD3D	Immunodeficiency 19 (IMD19)	615617	AR
CD3E	Immunodeficiency 18 (IMD18)	615615	AR
CD3G	Immunodeficiency 17, CD3 gamma deficient (IMD17)	615607	AR
CORO1A	Immunodeficiency 8 (IMD8)	615401	AR
DCLRE1C	Omenn syndrome \| Severe combined immunodeficiency, Athabascan type	603554 \| 602450	AR
FOXN1	T cell immunodeficiency, congenital alopecia, and nail dystrophy	601705	AR
IL2RA	Immunodeficiency 41 (IMD41) with lymphoproliferation and autoimmunity \| Diabetes, mellitus, insulin-dependent, 10, susceptibility to	606367 \| 601942	AR \| Mu
IL2RG	Combined immunodeficiency, X-linked, moderate \| Severe combined immunodeficiency, X-linked	312863 \| 300400	XLR
IL7R	Severe combined immunodeficiency, T cell negative, B cell/natural killer cell-positive type	608971	AR
JAK3	SCID, autosomal recessive, T-negative/B-positive type	600802	AR
LIG4	LIG4 syndrome \| Multiple myeloma, resistance to	606593 \| 254500	AR \| SMu
NHEJ1	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	611291	AR
PRKDC	Immunodeficiency 26 with or without neurologic abnormalities	615966	AR
PTPRC	Severe combined immunodeficiency, T cell-negative, B cell/natural killer-cell positive \| Hepatitis C virus, susceptibility to	608971 \| 609532	AR \| Mu
RAG1	Severe combined immunodeficiency, B cell-negative \| Combined cellular and humoral immune defects with granulomas \| Omenn syndrome	601457 \| 233650 \| 603554	AR
RAG2	Severe combined immunodeficiency, B cell-negative \| Combined cellular and humoral immune defects with granulomas \| Omenn syndrome	601457 \| 233650 \| 603554	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
Fischer, A. (2000). Severe combined immunodeficiencies (SCID). Clinical and Experimental Immunology, 122(2), 143–149. https://doi.org/10.1046/J.1365-2249.2000.01359.X
Immune deficiency foundation (IDF). Severe Combined Immune Deficiency and Combined Immune Deficiency. https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/severe-combined-immune-deficiency-and-combined-immune-deficiency. 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.
Rivers, L., & Gaspar, H. B. (2015). Severe combined immunodeficiency: recent developments and guidance on clinical management. Archives of Disease in Childhood, 100(7), 667–672. https://doi.org/10.1136/archdischild-2014-306425.