Altered Serum Cytokine Signature in Common Variable Immunodeficiency

Abstract

Purpose Common variable immunodeficiency (CVID) is the most frequent form of primary symptomatic hypogammaglobulinemia. CVID patients display a number of abnormalities in lymphocyte subpopulations including chronic T-cell activation and decreased numbers of circulating CD4+ T cells and NK cells. We and others have recently shown that CVID is associated with increased concentration of soluble CD14 (sCD14) and other factors indicating limited microbial translocation. Methods To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of cytokine serum levels in 36 patients with CVID, 52 patients with selective IgA deficiency (IgAD), and 56 healthy volunteers. Results We show that CVID is associated with elevated serum levels of CXCL-10/IP-10, IL-1R antagonist, TNF-α, IL-10, IL-12( p40), CCL-2/MCP-1, G-CSF, and CCL-11/eotaxin. The detected cytokine signature is consistent with an ongoing activation of cells of myeloid lineage. In contrast, the levels of cytokines typically produced by CD4+ T helper cells of Th1 (IFN-γ, IL-2), Th2 (IL-9, IL-13), and Th17 (IL-17) subtypes were suppressed in CVID patients compared to healthy donors. Conclusions Presented data suggest that the altered cytokine profile observed in patients with CVID may be attributed to the activation of monocyte-macrophage and granulocyte lineages, possibly driven by the translocation of bacterial components across the gastrointestinal or respiratory tracts mucosal barrier.

Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

“…The platelet production was decreased in healthy volunteers receiving rhIL-1031, implying that the high levels of IL-10 found in CVID-AcT patients could impair the platelet production. Increased levels of IL-10 in CVID were described previously48. However, the high levels of IL-10 observed seemed to be in contradiction to a study that reported decreased IL-10 production in ITP49.…”

Microbial translocation and T cell activation are modified by direct‐acting antiviral therapy in HCV‐infected patients

“…Immunological impairment can also lead to a less efficient intestinal barrier and increased microbial translocation as is the case in other conditions of immunodeficiency. [23][24][25] This may be supported by the observation that liver transplanted patients (group LT + ≥F2), receiving chronic immunosuppressive therapy, showed higher levels of microbial translocation respect to group ≥F3, in the absence of portal hypertension in the majority of them. Indeed, in group LT + ≥F2, sCD14, as well as other surrogate biomarkers of microbial translocation, tended to be higher than in group ≥F3.…”

T-Cell Abnormalities in Common Variable Immunodeficiency

“…CVID patients with hepatomegaly had higher IL-2 and IFN-γ levels in stimulated CD4 + T cells, and patients with granuloma were found to have higher CCR5 expression in CD4 + T cells, suggesting that T H 1 cells may play a role in granuloma formation in CVID patients [14]. Overall, increased production of some chemokines [56] and cytokines, including IFN-γ [57], TNF-α [12], IL-12 [57], IL-9 [49], IL-4, and IL-10 [58] by T H subsets has been reported in CVID patients [59]. Some of these cytokines play a pivotal role in antibody synthesis.…”