Immunoproteomic Analysis Of Mycobacterium Tuberculosis And Nontuberculous Mycobacteria Towards The Discovery Of Potential Universal Or Species Specific Biomarkers

The immunoproteomic analysis of whole cell protein (WCP) of Mycobacterium tuberculosis complex (MTBC) and non–tuberculous mycobacteria (NTM) was carried out to identify the potential species specific and cross genus conserved species biomarkers present in the mycobacterial species. The WCP of Mycobacterium species were separated using SDS-PAGE and followed by Western blot assay to detect IgM, IgG and IgA immune response in pooled sera of TB patients and healthy subjects as well as the individual sera. The immunoreactive bands in WB assay were divided into 4 region of antigens; (1) above 67 kDa; (2) 67 kDa – 32 kDa; (3) 30 kDa, 28kDa and 26 kDa; and (4) below 25 kDa

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Undertreatment and Underachievement of LDL-C Target among Individuals with High and Very High Cardiovascular Risk in the Malaysian Community

Dyslipidaemia is a major cause of morbidity and mortality. The aims of this study are to determine the prevalence of dyslipidaemia subtypes, the proportions of lipid-lowering therapy (LLT) use, and the achievement of low-density lipoprotein cholesterol (LDL-C) treatment targets for high-risk (HR) and very high-risk (VHR) Malaysians. This cross-sectional study involves 5279 participants across 11 states in Malaysia. The data were obtained through a standardised questionnaire, anthropometric measurements, venous glucose and lipid profile. The participants with existing cardiovascular disease (CVD) or diabetes with at least one of the other major risk factors (smoking, hypertension or dyslipidaemia) were grouped into the VHR category. Other participants were risk-categorised using the Framingham General CVD Risk Score (FRS-CVD). The prevalence of elevated LDL-C, LLT use and LDL-C target were set according to respective risk categories. Pearson’s chi-squared test was used to test the difference in the proportions. The mean ± standard deviation (SD) age was 41.1 ± 14.8 years, and 62.2% (3283/5279) of the group were females. Within the participant group, 51.5% were found to have elevated total cholesterol, 28.8% had low HDL-C, and 33.8% had high triglyceride. As for elevated LDL-C, 9.8% were in VHR, 8.6% in HR, 5.8% in MR and 34.9% in LR categories. Among the VHR group, 75.8% were not on LLT, and only 15.9% achieved the LDL-C target. As for the HR category, 87.7% were not on LLT, and only 16.1% achieved the LDL-C target. Dyslipidaemia is highly prevalent among Malaysians. The majority of VHR and HR participants were not on LLT and did not achieve LDL-C treatment targets. Proactive programs are warranted to combat dyslipidaemia-associated CVD events in these groups

Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing

Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening