The expansion of CD14+ CD163+ subpopulation of monocytes and myeloid cells-associated cytokine imbalance; candidate diagnostic biomarkers for celiac disease (CD)

J Clin Lab Anal. 2021 Oct;35(10):e23984. doi: 10.1002/jcla.23984. Epub 2021 Aug 27.

Abstract

Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated.

Methods: Here, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL-10, IL-12, TGF-β, and TNF-α cytokines using ELISA method, among 30 CD patients and 30 sex- and age-matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences.

Results: CD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL-10and TNF-α increased, and TGF-β expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL-10/IL-12 ratios were higher in CD patients, and TGFβ/TNFα ratio was higher in HS group. IL-10, CD14+CD163+, TNF-α, and IL-10/IL-12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed.

Conclusion: According to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD.

Keywords: CD163; biomarker; celiac disease; cytokine imbalance; monocytes.

MeSH terms

  • Adult
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Biomarkers / metabolism
  • Celiac Disease* / diagnosis
  • Celiac Disease* / immunology
  • Celiac Disease* / metabolism
  • Celiac Disease* / physiopathology
  • Cytokines / metabolism
  • Female
  • Humans
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Myeloid Cells / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD14 protein, human
  • CD163 antigen
  • Cytokines
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface