Monocyte plasticity and HLA-DR expression in patients with X-linked agammaglobulinemia


Artac H., Ceylan A., Kulhas Celik I., Celebi Celik F., KARALI Y., Meric Z., ...More

Immunologic Research, vol.73, no.1, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 73 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1007/s12026-025-09690-x
  • Journal Name: Immunologic Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Bruton’s tyrosine kinase, Monocyte HLA-DR, Monocyte plasticity, X-linked agammaglobulinemia
  • Marmara University Affiliated: Yes

Abstract

Bruton’s tyrosine kinase (BTK) is expressed by innate immune cells, and it has been suggested that a lack of BTK may affect monocytes, impacting infection susceptibility and inflammatory response in patients with X-linked agammaglobulinemia (XLA). This study aimed to explore the role of monocyte subsets and monocyte human leucocyte antigen DR (mHLA-DR) expression in patients with XLA. Fifty-nine patients diagnosed with XLA and 37 age-matched healthy subjects were enrolled, and their demographic and clinical features were recorded. Three monocyte subsets were identified—classical (CL) (CD14++CD16−), intermediate (INT) (CD14++CD16+), and non-classical (NC) (CD14lowCD16++)—and their mHLA-DR expressions (mean fluorescence intensity, MFI) were determined by flow cytometry. We evaluated monocyte plasticity as the classical/intermediate monocyte (CMIM) ratio. Patients with XLA comprised 38 children (mean age, 10.46 ± 4.81 years) and 21 adults (25.09 ± 6.18 years). Compared to the control group, patients had decreased classical (p =.012) but increased intermediate and non-classical monocytes (p <.001 and p =.048, respectively). They also presented with increased mHLA-DR expression of total monocytes and their subsets compared to the healthy subjects (p <.05). There were 17 patients with bronchiectasis (28.8% of total, three children and 14 adults), and they had decreased mHLA-DR of non-classical monocytes and a low CMIM ratio compared with non-bronchiectasis XLA patients (p <.001). The study findings may indicate that a defect in adaptive immune mechanisms leads to compensatory changes in the innate immune system. Monocyte HLA-DR expression and CMIM ratio can be used as potential biomarkers to predict chronic complications, including bronchiectasis in patients with XLA.