Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID)

Front Immunol. 2023 Sep 28:14:1257398. doi: 10.3389/fimmu.2023.1257398. eCollection 2023.

Abstract

Introduction: Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation.

Methods: In this study, we evaluated the serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD).

Results: Our results showed increased serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-α, IL-1β, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD.

Discussion: These findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects.

Keywords: CVID; IL-1; IL-10; IL-6; TNF-α; common variable immunodeficiency; lipopolysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Common Variable Immunodeficiency*
  • Cytokines*
  • Humans
  • Immunoglobulins
  • Interleukin-10
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha

Substances

  • Cytokines
  • Interleukin-10
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Lipopolysaccharides
  • Lipopolysaccharide Receptors
  • Immunoglobulins

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported in part by grants from the CISI-Lab Project (University of Naples Federico II), TIMING Project and Campania Bioscience (Regione Campania).