This page contains supplementary material for our High-Throughput GoMiner paper.

CVID Study Supplementary Materials

Differences in Expression of Individual Genes

It has been reported that Mcp-/- mice are unable to mount type 2 helper cell (TH2) responses [1]. Lymph node cells from immunized Mcp-/- mice synthesize extremely low levels of interleukin-4, interleukin-5, and interleukin-10 but normal amounts of interferon-gamma and interleukin-2. Consequently, those mice do not accomplish the immunoglobulin subclass switch. Gu et al. [1] have concluded that MCP1 influences both innate immunity (through effects on monocytes) and adoptive immunity (through control of T-helper cell polarization). The defective humoral immunity in the CVID patient may have been caused in part by a skewed response of T cell help away from the TH2 pathway toward the TH1 pathway. That possibility is reflected in the low expression of chemokine CCL2 (also named monocyte chemotactic protein 1, or MCP1), which is present in almost all of the significant categories (Figure 3 - see paper).

PTPNS1 (MYD1), a dendritic cell surface antigen, has been reported to affect activation of T lymphocytes [2]. The low expression of PTPNS1 (Figure 3 - see paper), which is present in only the �cell adhesion� category (enrichment = 3.3; p= 10-2.1; FDR = 0.01), may be associated with impaired CD4+ T cell activation during the immune response.

The underexpressed gene HLA-DRA is a member of a number of important categories including �antigen presentation� (enrichment = 12.8; p = 10-2.0; FDR = 0.10), �antigen processing� (enrichment = 12.8; p = 10-2.0; FDR = 0.10), �defense response� (enrichment = 3.2; p = 10-4.8; FDR = not detectable), and �immune response� (enrichment = 3.4; p = 10-5.1; FDR = not detectable), as indicated in Figure 3 (see paper) and Gene Category Report. HLA-DRA is an MHC class II gene. MHC class II genes are critical for antigen recognition by the immune system, and absence of constitutive and inducible MHC class II gene expression causes severe combined immunodeficiency (SCID) [3]. The absence of HLA-DRA may contribute to the phenotype of CVID in some patients [4-6].


  1. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 2000, 404:407-411.
  2. Brooke GP, Parsons KR, Howard CJ. Cloning of two members of the SIRP alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells. Eur J Immunol. 1998, 28:1-11.
  3. Nekrep N, Fontes JD, Geyer M, Peterlin BM: When the lymphocyte loses its clothes. Immunity. 2003, 18:453-457.
  4. Rozynska KE, Spickett GP, Millrain M, Edwards A, Bryant A, Webster AD, Farrant J: Accessory and T cell defects in acquired and inherited hypogammaglobulinaemia. Clin Exp Immunol. 1989, 78:1-6.
  5. Eibl MM, Mannhalter JW, Zlabinger G, Mayr WR, Tilz GP, Ahmad R, Zielinski CC: Defective macrophage function in a patient with common variable immunodeficiency. N Engl J Med. 1982, 307:803-806.
  6. Farrant J, Bryant AE, Lever AM, Edwards AJ, Knight SC, Webster AD: Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells. Clin Exp Immunol. 1985, 61:189-194.

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