Common variable immunodeficiency: how many diseases?

SUMMARYMost cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have ®rst degree relatives with IgA de®ciency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic background with IgAD in our population. Patients with CVID (n 42), were typed using gene ampli®cation and sequence-speci®c oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association between non-Asp residues at position 57 of the HLA-DQb chain and CVID, although much weaker than in IgAD. Further, we found an association between CVID and homozygosity for genes encoding HLA class II molecules, especially HLA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVID.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID)

Concha¹,

Fernández‐Arquero²,

Martínez³

et al. 1999

“…There is considerable heterogeneity in the CVID population, and efforts have been made to define discrete subgroups of CVID [27,28], ultimately to elucidate yet-unknown pathogenetic mechanisms in CVID. In many CVID patients impaired T cell function has been observed [4], often assessed using in vitro thymidine incorporation in T cells.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of peripheral T cells in a subgroup of common variable immunodeficiency shows predominance of CCR7– effector-memory T cells

Holm

Sivertsen

Tunheim

et al. 2004

SUMMARYCommon variable immunodeficiency (CVID) represents a heterogeneous group of antibody deficiency syndromes, characterized by defective antibody production in which T cell deficiency may play a pathogenic role. A subgroup of CVID patients has impaired in vitro T cell proliferation. Using microarray analyses of T cells from these patients, we found a gene expression pattern different from healthy controls and patients with X-linked agammaglobulinaemia. The profile of the differentially expressed genes suggests enhanced cytotoxic effector functions, antigen experienced or chronically activated T cells and a predominance of CCR7 -T cells. Further experiments using flow cytometry revealed a striking predominance of CCR7 -T cells in a subgroup of CVID patients, and an association with impaired T cell proliferation. Our observations indicate that a predominance of CCR7 -T cells with effector-memory cell features and with reduced proliferative capacity may characterize a subgroup of CVID.

“…These patients represent both clinically and immunologically a heterogeneous group [2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Adhesion molecules in common variable immunodeficiency (CVID)—a decrease inl-selectin-positive T lymphocytes

Nordøy¹,

Müller²,

Aukrust³

et al. 1998

SUMMARYCVID is immunologically characterized by defective antibody production. Various additional immunological abnormalities have been reported, but little is known of the role of adhesion molecules in CVID. In 31 CVID patients serum levels of L-selectin (CD62L), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54) were significantly elevated compared with controls. In 15 CVID patients investigated, the number of L-selectin-positive cells was significantly reduced in both CD4 þ and CD8 þ lymphocytes compared with controls, and these changes were observed in both CD45RA þ and CD45RO þ subsets. In CD19 þ lymphocytes the percentage of ICAM-1 þ cells was significantly increased compared with controls. Fifty percent of the patients had splenomegaly. These patients demonstrated even higher serum levels of adhesion molecules, a lower percentage of L-selectin-positive and a higher percentage of CD38 þ cells in many T lymphocyte subsets compared with both other CVID patients and controls. Finally, in this patient group the percentage of L-selectin-positive CD19 þ lymphocytes was significantly reduced compared with both other patients and controls. These findings indicate a state of ongoing T lymphocyte activation in CVID, especially in the subgroup of patients with splenomegaly, which may contribute to the impaired antimicrobial defence observed in these patients.