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

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.

CD64 expression on polymorphonuclear cells as a potential marker for monitoring the human cytomegalovirus replication after kidney transplantation / Expressão de CD64 em polimorfonucleares como potencial marcador para o monitoramento da replicação do citomegalovírus humano após transplante renal

ABSTRACT Human cytomegalovirus (HCMV) infection is the main cause of morbidity in kidney transplant recipients. This study aims to investigate if CD64 expression on polymorphonuclear (PMN) cells is useful for the detection of HCMV infection in eleven kidney recipients during sixty days. From the total patients, nine were positive for both pp65 antigenemia and HCMV by quantitative polymerase chain reaction (qPCR), all of which had circulating neutrophils expressing CD64 3-4 weeks prior to pp65 antigenemia peak. These results suggest that quantification of PMN CD64 together with pp65 antigenemia could be useful for the early diagnosis of HCMV after transplantation.

RESUMO A infecção por citomegalovírus humano (CMVH) é a principal causa de morbidade em receptores de transplante renal. Este estudo pretende investigar se a expressão de CD64 em polimorfonucleares (PMN) é útil para a detecção de infecção por CMVH em 11 receptores renais durante 60 dias. Do total de pacientes, nove foram positivos para antigenemia pp65 e para CMVH por reação em cadeia da polimerase quantitativa (qPCR), todos apresentando neutrófilos circulantes que expressam CD64 3-4 semanas antes do pico de antigenemia pp65. Esses resultados sugerem que a quantificação de PMN CD64 em conjunto com a antigenemia pp65 pode ser útil para o diagnóstico precoce de HCMV no pós-transplante.