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

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.

Authors: Artac H, Ceylan A, Kulhas Celik I, Celebi Celik F, Karali Y, Meric Z, Tekcan D, Geyik M, Bozkurt S, Esenboga S, Haskolo&amp;#x11f;lu Z&amp;#x15e;, Ozek Yucel E, Gulez N, Edeer Karaca N, Bilgic Eltan S, Guner SN, Aydogmus C, Celiksoy MH, Karabiber E, Genel
Journal: Immunol Res;2025Sep19; 73 (1) 133. doi:10.1007/s12026-025-09690-x
Year: 2025
PubMed: PMID: 40970998 (Go to PubMed)