Loading ......
Lipoarabinomannan (LAM) is a significant component of the cell wall in Mycobacterium tuberculosis (MTB), the bacterium responsible for causing tuberculosis (TB). LAM plays a crucial role in the virulence and pathogenesis of MTB, making it an important target for research and potential therapeutic interventions.
The cell envelope of Mycobacterium tuberculosis (MTB) consists of four distinct regions, arranged from the innermost to the outermost layers: the plasma membrane with its glycolipids, the periplasm with assembling proteins, the cell wall with peptidoglycan and arabinogalactan, and the capsule with its matrix of glucans and secretory proteins. In the plasma membrane, there are anchored phosphatidylinositol mannosides (PIMs), which serve as the fundamental structure for lipomannan (LM), LAM, and mannosylated LAM (manLAM). Proteins such as EmbC, PonA1, or LDT2 play a role in the elongation process of LAM by assisting in its assembly.
LAM derived from virulent strains of MTB exhibits a four-domain structure. It begins with a phosphatidyl-myoinositol anchor attached to the plasma membrane, serving as the foundation for the mannan backbone. This is followed by the arabinofuranose backbone and capping motifs, which may include extra-mannoses, methylthio-D-xylose, or arabinofuranosides. The arrangement and composition of these domains contribute to the unique structure and properties of LAM in virulent MTB strains.
Figure 1. Schematic organization of LAM in the Mycobacterial cell envelope.
(Source: Flores, J. et al., 2021)
ManLAM is a specific type of LAM that is commonly found in highly pathogenic Mycobacterium species like M. tuberculosis, M. leprae, and M. bovis. ManLAM has unique characteristics, including the presence of mannosyl caps on the terminal D-arabinan. In previous studies, it has been observed that ManLAM exhibits anti-inflammatory properties by inhibiting the production of TNF-α and IL-12 in human dendritic cells and macrophages. Additionally, ManLAM interacts with host macrophage mannose receptors, leading to the deactivation of macrophages and allowing the bacteria to survive and multiply within them.
The diagnostic potential of LAM in TB has garnered significant attention in recent years. Several diagnostic approaches have been developed to detect LAM in patient samples, offering the potential for a rapid and accurate TB diagnosis. Urinary LAM testing can serve as an important diagnostic tool, and antigenic LAM has the potential advantage of reflecting mycobacterial load. Moreover, compared with sputum, urine is safer to process in the laboratory. Studies have shown that urine LAM testing has the potential to improve the diagnostic rate of TB patients co-infected with HIV. The lateral flow lipoarabinomannan assay (LF-LAM) recommended by the World Health Organization in 2016 to measure LAM is suitable for HIV-positive tuberculosis patients with CD4+T lymphocytes≤100 cells/μL. However, this method is less sensitive. The majority of TB patients worldwide are HIV-negative, and it is important to find suitable testing methods for this population.
One of the notable advancements in urine-based diagnostics is the Fujifilm SILVAMP TB LAM assay. This point-of-care test uses high-affinity monoclonal antibodies directed against major MTB-specific LAM epitopes and adds a silver amplification step. The test is 75% sensitive to detecting TB in adults and 64% sensitive to children. This kit is suitable for clinical diagnosis of HIV-positive tuberculosis patients and also has diagnostic value for children with tuberculosis patients in poor physical condition.
Additionally, advancements in technology have led to the development of more sensitive and specific LAM-based diagnostic tools. For example, enzyme-linked immunosorbent assays (ELISAs) have been developed to detect LAM in various clinical samples, including serum, urine, and cerebrospinal fluid. These assays utilize LAM-specific antibodies and provide quantitative measurements, aiding in the monitoring of disease progression and treatment response.
Although LAM has broad diagnostic potential, considering some limitations, LAM-based testing is often used as a complementary tool with other tuberculosis diagnostic methods such as smear tests and microbial cultures. The current proposed strategies for using LAM as a point-of-care test for TB diagnosis indicate that further efforts are needed to optimize its effectiveness. Several disadvantages need improvement, including the sensitivity of the technique, the interaction of LAM with cells or soluble molecules, and the structural changes that can occur in LAM.
References
| Target | Cat. No. | Product Name | Size | Species Reactivity | Application | Detection Sample | |
| TNF-alpha | ABPR-ZB157 | Human TNF-alpha Antibody Pair Set | 5 Plates, 15 Plates | Human | sELISA | Inquiry | |
| ABPR-ZB242 | Mouse TNF-alpha Antibody Pair Set | 5 Plates, 15 Plates | Mouse | sELISA | Inquiry | ||
| ABPR-ZB305 | Ferret TNF-alpha Antibody Pair Set | 5 Plates, 15 Plates | Ferret | sELISA | Inquiry | ||
| IL-12 | DEIA-T6107 | Porcine Interleukin 12 (IL-12) ELISA Kit | 96T | Swine | Quantitative | Serum, Plasma, Tissue Homogenates and other Biological Fluids. | Inquiry |
| Macrophage | DEIA-BJ501 | Human Macrophage Inflammatory Protein 1a ELISA kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | |
| DEIA-BJ557 | Human Macrophage inflammatory protein-3α ELISA kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | ||
| HIV | DEIA10155 | HIV-1 p24 ELISA Kit | 96T | Human | Quantitative | Tissue culture supernatants | Inquiry |
| DEIA064 | Antibody to Human Immunodeficiency Virus(1+2) ELISA Kit | 96T | Human | Qualitative | serum, plasma | Inquiry | |
| DEIA066 | Human Immunodeficiency Virus (1+2) Antigen and Antibody ELISA Kit | 96T | Qualitative | serum, plasma | Inquiry | ||
| DEIA2359 | Human HIV 1&2 Ag/Ab ELISA Kit | 96T | Human | Qualitative | serum, plasma | Inquiry | |
| DEIA3571 | Lentivirus Titer Kit, HIV-1 p24 ELISA | 96T | Virus | Quantitative | Tissue culture supernatants | Inquiry | |
| IVDEIA002 | Human anti-HIV 1+2 ELISA Kit | 96T | Qualitative | serum, plasma | Inquiry | ||
| DEIASL616 | HIV-1 gp120 Clade C ELISA Development Kit | 5 x 96T | quantitative | serum, cell culture supernatants | Inquiry |
Loading ......