Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease

Abstract

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1

“…Furthermore, it was suggested that TB disease dramatically alters neutrophils, leading to the accumulation of heterogeneous subpopulations of immature and activated dysfunctional cells [27,35,36], although their occurrence during human TB and the role of SLAMF1 remains to be investigated. Besides, the development of TB is multifactorial, and genetic causes might…”

Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice

“…Previous studies have reported that patients with active pulmonary TB elicited the elevation of levels of IgG1 and IgG3 subclasses in sera ( Correa et al., 2019 ), which played important roles in complement activation ( Jovic and Cymer, 2019 ). We found that the levels of complement C3 and C5 decreased slightly in sera of CnpB immunized mice ( Figure 5C ), but levels of complement C3 in homogenates of lungs and spleens remained unchanged ( Figure 5D ), suggesting that high levels of IgG subclasses might activate and deplete complement system through the classical pathway.…”

Tuberculosis comorbidity with rheumatoid arthritis: Gene signatures, associated biomarkers, and screening

“…So, CD64 can be recommended as an early diagnostic marker in infections 57 . The high expression level of CD64 has been shown in active TB than LTBI and healthy donors with high sensitivity and specificity 58 . In RA patients undergoing anti‐biologic medications, the expression of CD64 was upregulated on neutrophils in patients with various infections than those without infections 59 .…”