ABSTRACT
BACKGROUND: The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically review MLR and NLR as biomarkers for diagnosis, treatment response monitoring and prognostic biomarker for TB infection or disease.METHODS: A systematic literature search was conducted in Medline, Embase and the Cochrane Library on 12 January 2022. The following search terms were used: tuberculosis AND (monocyte OR neutrophils), AND lymphocytes AND (diagnostic OR prognostic OR treatment).RESULTS: A total of 2,314 studies were identified, of which 41, covering 11,952 individuals, were included in the final analysis. Studies enrolled a median of 154 individuals (IQR 108-301). Increased MLR and NLR were associated with TB disease when compared to healthy controls and individuals with TB infection. MLR was shown to be prognostic for progression to TB disease and to decrease in response to TB treatment. The cut-offs determined in the studies were highly variable for MLR and NLR, making it impractical to conduct a meta-analysis of sensitivity and specificity.CONCLUSION: Higher MLR and NLR are associated with TB disease and could be used as easy-to-obtain, low-cost additional diagnostic biomarkers. Further studies investigating these biomarkers are needed.
Subject(s)
Lymphocytes , Monocytes , Tuberculosis , Humans , Biomarkers , Neutrophils , Prognosis , Retrospective Studies , Tuberculosis/diagnosis , Tuberculosis/therapyABSTRACT
BACKGROUND: The extent to which individuals exhibit genetic susceptibility to tuberculosis (TB) is still unclear. Genetic variations in chemokine genes might influence the early clearance of Mycobacterium tuberculosis, affecting TB susceptibility. OBJECTIVES: To study single nucleotide polymorphisms (SNPs) of chemokine genes CCL2, CXCL9, CXCL10 and CXCL11, and their association with TB susceptibility. DESIGN: Of 248 participants enrolled, 49 had active TB, 43 had latent tuberculous infection (LTBI) and 156 were non-infected, including 24 healthy controls with no known TB exposure. These populations were divided into two groups based on TB exposure: susceptible (n = 92) and resistant (early clearance) (n = 132). RESULTS: Only CCL2 SNPs (-2518A/G) were significantly associated with increased TB susceptibility. Based on adjusted multivariate analysis, persons with the GG genotype at this SNP were twice as susceptible to TB as those with the AA genotype (P = 0.018, OR 2.880, 95%CI 1.201-6.903). Risk of LTBI was three times higher among those with GG (P = 0.003, OR 3.358, 95%CI 1.525-7.396 for AA+AG vs. GG and P = 0.012, OR 3.706, 95%CI 1.340-10.254 for AA vs. GG). Persons with the GG genotype produced significantly lower CCL2 levels in response to M. tuberculosis antigen stimulation (AA+AG vs. GG, P = 0.038). CONCLUSION: The CCL2 polymorphism (-2518A/G) was associated with susceptibility to LTBI in a North-East Thai populations.
Subject(s)
Chemokine CCL2/genetics , Genetic Predisposition to Disease , Latent Tuberculosis/genetics , Adult , Antigens, Bacterial/blood , Asian People/genetics , Body Mass Index , Case-Control Studies , Chemokine CXCL10/genetics , Chemokine CXCL11/genetics , Chemokine CXCL9/genetics , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , ThailandABSTRACT
BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/µl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.
Subject(s)
HIV Infections/immunology , Receptors, KIR/genetics , Adult , Alleles , CD4-Positive T-Lymphocytes/immunology , Cohort Studies , Disease Progression , Female , HIV Infections/diagnosis , HLA-C Antigens , Haplotypes , Humans , Killer Cells, Natural/immunology , Prospective Studies , South Africa , Viral LoadABSTRACT
The effector function of natural killer (NK) cells is modulated by surface expression of a range of killer-cell immunoglobulin-like receptors (KIRs) that interact with human leukocyte antigen (HLA) class I ligands. We describe the use of real-time polymerase chain reaction (PCR) assays that allow easy and quick detection of 16 KIR genes and the presence/absence of KIR-ligands based on allelic discrimination at codon 80 in the HLA-A/B Bw4 and HLA-C C1/C2 genes. These methods overcome the tedious and expensive nature of conventional KIR genotyping and HLA class I typing using sequence-specific primer (SSP) PCR, sequence-specific oligonucleotide (SSO) hybridization or sequence-based typing (SBT). Using these two cost-effective assays, we measured the frequencies of KIRs, KIR-ligands and KIR/KIR-ligand pairs in a cohort of Black women recruited in South Africa.
