Adiponectin Receptors and Pro-inflammatory Cytokines Are Modulated in Common Variable Immunodeficiency Patients: Correlation With Ig Replacement Therapy

Abstract

Adiponectin exerts beneficial pleiotropic effects through three receptors, AdipoR1, AdipoR2, and T-cadherin; it also exerts immunomodulatory effects. We previously demonstrated that adiponectin levels are altered in common variable immunodeficiency disease (CVID). The purpose of the present study was to investigate further the specific involvement of adiponectin in CVID by characterizing (i) the expression profile of adiponectin receptors on peripheral blood mononuclear cells; (ii) the levels of another relevant adipokine, namely leptin; (iii) the levels of five other cytokines (IL-2, IL-6, IL-10, TNFα, and IFNγ) in 24 patients on maintenance therapy, in 18 treatment-naïve patients (before and 24 h after the first Ig infusion) and in 28 healthy controls. We found that (i) adiponectin was down-expressed in patients on maintenance therapy and in treatment-naïve patients, and that it increased in treatment-naïve patients 24 h after the first Ig infusion; (ii) leptin expression did not differ between maintenance patients and controls either before or after the first Ig infusion; (iii) AdipoR1 expression was significantly higher on B lymphocytes, monocytes and NK cells of CVID patients than in controls; (iv) the expression of AdipoR1 and AdipoR2 on B lymphocytes, monocytes and NK cells was higher after the first Ig infusion than in treatment-naïve patients; (v) T-cadherin expression did not differ between treatment- naïve CVID patients and controls, and was not affected by Ig infusion; and (vi) IL-6, IL-8, IL-10, and TNFα levels were differently expressed in CVID patients on therapy maintenance and were not affected by the first Ig replacement therapy. This is the first study to demonstrate that the expression of AdipoRs in peripheral blood mononuclear cells from CVID patients differs from that of controls, and changes after the first Ig infusion. The specificity of adiponectin involvement in CVID is supported by the absence of changes in leptin levels and in the levels of the cytokines investigated. Taken together, these results suggest that the adiponectin system plays an important and specific role in CVID. A better understanding of adiponectin as a link in the cross-talk between the immune system and adipose tissue may provide additional benefits for the management of CVID patients.

Exploring the New Horizon of AdipoQ in Obesity-Related Alzheimer’s Dementia

“…A study reported the decreased expression of total AdipoQ and its high molecular weight oligomers in patients with common variable immunodeficiency ( Pecoraro et al, 2017 ). A further study also revealed different expression patterns of AdipoQR1 and AdipoQR2 in the peripheral blood mononuclear cells of these patients ( Polito et al, 2019 ).…”

Targeted Proteomics Reveals Inflammatory Pathways that Classify Immune Dysregulation in Common Variable Immunodeficiency

“…For example, IL10 is often found to be upregulated in CVID as compared to healthy controls [17,18], but in a different cohort, a decrease of serum IL10 was described [19]. Overall, markers associated with an activated myeloid compartment are consistently upregulated in CVID [18][19][20], and the T-helper (Th) serum cytokine profile observed in immune dysregulation in CVID is mostly found to be Th-1 driven [17,18,21]. Varying findings in these studies highlight the need to consider CVID patients with immune dysregulation (CVIDid) separately from patients with an "infection only" (CVIDio)phenotype.…”

Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients

“…IgG, IgM and IgA levels have been measured before and after the first Ig replacement therapy: the increase of levels of IgG is statistically significant as previously reported in patients with common variable immunodeficiencies and patients with X-linked agammaglobulinemia 13 (Table 1). To verify the specific changes that taken place after the first IgG infusion therapy, we measured Adiponectin after 24 h as we previously reported that modification in the adiponectin levels are already evident at 24 h postinfusion and therefore we considered adiponectin as a marker of functional changes post-infusion 5,6 . We confirmed that adiponectin but not leptin was statistically different at T0 and T1 post-IgG infusion (4.3 ± 4.53 vs 12.84 ± 8.78, respectively, p < 0.01).…”

“…Various studies have been devoted to characterize the cytokines profile in CVID, albeit with conflicting results [4][5][6] . We recently reported that adiponectin is decreased in CVID and correlated to the first Ig infusion, representing a serum biomarker of functional changes taking place in the adipose and related to the replacement therapy 7 .…”