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<p>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<sup>++</sup>CD16<sup>−</sup>), intermediate (INT) (CD14<sup>++</sup>CD16<sup>+</sup>), and non-classical (NC) (CD14<sup>low</sup>CD16<sup>++</sup>)—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&#xa0;years) and 21 adults (25.09 ± 6.18&#xa0;years). Compared to the control group, patients had decreased classical (<i>p</i> = .012) but increased intermediate and non-classical monocytes (<i>p</i> &lt; .001 and <i>p</i> = .048, respectively). They also presented with increased mHLA-DR expression of total monocytes and their subsets compared to the healthy subjects (<i>p</i> &lt; .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 (<i>p</i> &lt; .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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • Hasibe Artac,
  • Ayca Ceylan,
  • Ilknur Kulhas Celik,
  • Figen Celebi Celik,
  • Yasin Karali,
  • Zeynep Meric,
  • Demet Tekcan,
  • Mehmet Geyik,
  • Selcen Bozkurt,
  • Saliha Esenboga,
  • Zehra Şule Haskoloğlu,
  • Esra Ozek Yucel,
  • Nesrin Gulez,
  • Neslihan Edeer Karaca,
  • Sevgi Bilgic Eltan,
  • Sukru Nail Guner,
  • Cigdem Aydogmus,
  • Mehmet Halil Celiksoy,
  • Esra Karabiber,
  • Ferah Genel,
  • Esin Figen Doğu,
  • Elif Karakoc-Aydiner,
  • Deniz Cagdas,
  • Guzide Aksu,
  • Ayca Kiykim,
  • Sara Sebnem Kilic,
  • Sevgi Keleş,
  • Kamile Aydan Ikinciogullari,
  • İsmail Reisli

摘要

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.