Hematological Parameters as Potential Markers for Distinguishing Pulmonary Tuberculosis from Genitourinary Tuberculosis.

Mycobacterium tuberculosis complex (MTBC) infection is an important public health concern in Taiwan. In addition to pulmonary tuberculosis (PTB), MTBC can also cause genitourinary tuberculosis (GUTB). This study aimed to examine the role of laboratory data and the values that can be calculated from them for the early detection of GUTB. Patients admitted from 2011 to 2020 were retrospectively recruited to analyze their associated clinical data. Statistical significance was analyzed using the chi-square test and univariate analysis for different variables. A receiver operating characteristic (ROC) curve analysis was used to evaluate the performances of the examined laboratory data and their calculated items, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR), and platelet-to-lymphocyte ratio (PLR), in diagnosing PTB or GUTB. A p-value of <0.05 was considered significant. The ROC curve showed that the discriminative power of the neutrophil count, NLR, and MLR was within the acceptable level between patients with both PTB and GUTB and those with GUTB alone (area under the curve [AUC] values = 0.738, 0.779, and 0.725; p = 0.024, 0.008, and 0.033, respectively). The discriminative power of monocytes and the MLR was within the acceptable level (AUC = 0.782 and 0.778; p = 0.008 and 0.010, respectively). Meanwhile, the neutrophil and lymphocyte counts, NLR, NMLR, and PLR had good discriminative power (AUC = 0.916, 0.896, 0.898, 0.920, and 0.800; p < 0.001, <0.001, <0.001, <0.001, and 0.005, respectively) between patients with GUTB and those with PTB alone. In conclusion, the neutrophil count, lymphocyte count, NLR, NMLR, and PLR can be used as potential markers for distinguishing PTB from GUTB.

Reappraisal of VEGF in the Pathogenesis of Kawasaki Disease.

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients.

Interleukin-18 and coronary artery lesions in patients with Kawasaki disease.

BACKGROUND: Interleukin-18 (IL-18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL-18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL-18 and CALs in patients with KD. METHODS: In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL-18 levels in the acute, subacute, and convalescent phases. Serum IL-18 levels were measured with a Bio-Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. RESULTS: Compared with febrile controls, patients with acute-stage CALs [postintravenous immunoglobulin (post-IVIG) period] had a significantly higher IL-18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute-stage CALs (post-IVIG period) lacked similarly elevated IL-18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL-18 level of patients with acute-stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL-18 level between patients with and without acute-stage CALs (p = 0.048). CONCLUSION: Our data show that IL-18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.

IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan.

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (-1082, -819, and -592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci -819 T > C and -592 A > C for KD cases was observed (P permutation = 0.029 and P permutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090-2.443; P permutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. The haplotype CC (-819, -592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987-1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and -592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.

IL-10 polymorphisms are associated with coronary artery lesions in acute stage of Kawasaki disease.

BACKGROUND: The literature regarding interleukin (IL)-10 polymorphisms and coronary artery lesions (CALs) in Kawasaki disease (KD) is limited. We investigated whether 3 IL-10 genetic polymorphisms (-1082 A/G, -819 T/C, and -592 A/C) are associated with development of CALs in KD. METHODS AND RESULTS: The genotyping of IL-10 polymorphisms was conducted for 279 KD children (172 without and 107 with CALs in acute stage). Thirty-three patients had CALs in chronic stage and 74 only with transient CALs. The homozygous variant genotype CC of IL-10-819 and IL-10-592 was associated with 80% (P=0.006) and 79% (P=0.008) reduction in risk of CALs in acute stage, respectively. The C allele of IL-10-819 and IL-10-592 was associated with 34% (P=0.034) and 33% (P=0.044) reduction in risk of CALs in acute stage, respectively. Compared with ATA haplotype (adjusted odds ratio (AOR) 0.63, P=0.029) or non-ACC haplotype (AOR 0.64, P=0.033), ACC haplotype was associated with a significantly reduced risk for CALs in acute stage, but not for CALs in chronic stage. Compared with non-ATA haplotype (AOR 1.53, P=0.034), ATA haplotype was associated with a significantly increased risk of CALs, except for CALs in the chronic stage. CONCLUSIONS: The effects of IL-10 gene polymorphism on CALs in acute KD are important. The persistence of CALs in chronic stage depends much more on other factors such as the times of intravenous immunoglobulin treatment.