TNF cytokine levels in CD4 and CD8 T cells in subgroups of common variable immunodeficiency patients (CVID)

Cellular immunity was examined in 36 patients with CVID. Based on clinical criteria, six of these were classified into a granulomatous group (gCVID) and thirty into a non-granulomatous group (ngCVID). Controls included healthy adults (n=22) and patients with sarcoid (n=4) and Crohn' s (n=9) disease. Using an intracellular cytokine assay, the TNF-alpha profile of peripheral blood CD4 and CD8 T lymphocytes were examined in all groups. The gCVID group exhibited a strong Th1 skewing with increased frequencies of CD4+/TNF-alpha + (p< 0.03) T cells compared to normal controls and significantly increased frequencies of CD4+/TNF-<alpha> + (p<0.03) compared to ngCVLD. Sarcoid patients displayed a similar strong TNF-<alpha> skewing in CD4 and CD8 T cells whereas neither ngCVID nor Crohns patients showed this higher T cell production of TNF-alpha. gCVID patients had raised serum levels of TNF-alpha compared to normals (p<0.03) and to ngCVID (p<0.07). gCVID and ngCVID patient groups had raised serum TNFR2 levels (p<0.02, p<0.01) compared to normals and serum TNFR2 levels were significantly higher in gCVID versus ngCVID (p<0.02). Genotyping of TNF-<alpha> haplotypes revealed a higher frequency of TNF-alpha haplotype TNF2 (containing TNF-alpha -308A allele) among CVID than in normal controls. The TNF3 haplotype (+488A allele) had a higher frequency in sarcoid patients than in CVID or normal controls, although TNF3 allele frequency was higher in gCVID than in ngCVLD. Preliminary studies suggest that possession of the TNF3 haplotype may be associated with increased frequencies of CD8+/TNF-alpha + peripheral blood T cells.