Immunodeficiency, Common Variable, 7

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Retrieved

2019-09-22

Source

Omim

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Genes

ICOS, NFKB2, TNFRSF13B, CD19, CR2, TNFRSF13C, NFKB1, CD81, MS4A1, CTLA4, IL21, IKZF1, IRF2BP2, TNFSF12, PRKCD, IL2RA, HAVCR1, GPR35, FGF14, LAMB4, ADGRL2, SRPX, ATXN2L, FUT2, CRB1, CARD9, ERAP2, TNFSF15, ZNF630, ZMIZ1, CDK14, MAN1C1, ATG16L1, NKD1, IGF2-AS, TNF, SMAD3, ADCY7, SUOX, ANKRD55, FNBP1, IRF1-AS1, C1orf141, KANTR, LINC00993, LINC01250, GNG12-AS1, ANKRD30A, DAG1, INS-IGF2, OR14J1, LRRK2, IL23R, TAB3, SNX31, LURAP1L, CACNA1C, CD27, TNFSF13B, CD40LG, FOXP3, SH2D1A, BTK, IL10, TLR9, TNFSF13, IL6, IL2, IFNG, LRBA, CD40, TLR4, BCL2, HLA-A, ANP32B, MBL2, TLR2, RAG1, CCR7, IGAD1, TRBV20OR9-2, STAT3, IL4, AICDA, ISG20, IFNA1, IFNA13, SBDS, VAV1, FCGR2A, APCS, FCGR3A, ICOSLG, TNFRSF8, FCGR3B, FCGRT, IGHG3, BCL6, POMC, BCR, SERPINA1, HLA-DQB1, IRF4, MTA2, TNFRSF18, HLA-C, IL22, ADIPOQ, CD38, CD86, TBX19, EBI3, ACTB, SWAP70, CLEC16A, CENPX, NLRP12, IL33, CARD11, NEIL1, NOD2, SCYL1, ARHGEF7, IFNK, KRT20, TOLLIP, TLR7, ADIPOR1, ASCC1, IL21R, NT5C, IGHV3-75, CLDN15, SMUG1, CLDN2, PRKAR1A, IL18R1, GEM, DPP4, DUSP5, CELSR3, FCN2, FUS, GATA3, HFE, CHIT1, HLA-B, HLA-DQA1, HLA-DRB1, HLA-DRB3, HSPG2, IL5, DNMT1, CDH13, IL17A, CXCR5, AIC, XIAP, FAS, AR, TNFRSF17, BLK, CAMLG, CD70, CASP3, CASP9, CD1D, CD14, CD28, CD69, IL7, ITGAM, BHLHE40, TCOF1, CCL19, CCL21, XCL1, SDC1, STAT5A, STAT5B, TERT, PTPRC, TNFRSF1B, TP53, UCHL1, VDR, XBP1, CDR3, RAG2, POU2AF1, ITGAX, MPO, ITK, KIR2DS1, KIR3DL1, KIR3DL2, LCK, LTA, MRC1, PIK3CD, MSH5, MYD88, NCAM1, NEDD9, ORC4, PAX5, H3P40

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A number sign (#) is used with this entry because common variable immune deficiency-7 (CVID7) can be caused by compound heterozygous mutation in the CD21 gene (CR2; 120650) on chromosome 1q32.

For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).

Clinical Features

Thiel et al. (2012) reported a 28-year-old man who presented with persistent myalgias, fever, sore throat, respiratory tract infections, and chronic diarrhea associated with Haemophilus influenza infection. He had a history of recurrent respiratory infections in childhood that resolved after tonsillectomy. Clinical examination as an adult showed splenomegaly. Laboratory studies showed hypogammaglobulinemia affecting mainly IgG; IgA values were slightly reduced and IgM levels were low-normal. Antibodies against recall antigens, such as measles, mumps, and varicella, were normal, and he had antibodies against EBV. The patient was diagnosed with an incipient CVID syndrome. Flow cytometric analysis showed complete absence of CD21 antigen in the patient's B cells. The B cells showed a mature antigen phenotype, but there was a reduction in class-switched memory B cells. Patient B cells showed reduced binding to a C3d (see 120700)-containing immune complex and to EBV compared to control cells, and also showed no costimulatory activity via the B-cell receptor complex. Patient cells showed normal proliferative response and production of immunoglobulin on stimulation with anti-IgM and anti-CD40 (109535), and the patient mounted a normal antibody response to protein vaccination, although his response to pneumococcal polysaccharide vaccination was somewhat impaired.

Molecular Genetics

In a patient with a mild form of combined variable immunodeficiency, Thiel et al. (2012) identified compound heterozygous mutations in the CD21 gene (120650.0002 and 120650.0003). Both mutations caused functionally null alleles, with lack of CD21 expression on the patient's B cells. Together with the demonstrated defects in CD19 (107265) and CD81 (186845), this CD21 deficiency was the third genetic defect affecting the B-cell coreceptor complex in humans. All 3 defects share the features of severely decreased memory B-cell numbers, hypogammaglobulinemia, and recurrent infections.