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Wednesday 11 September 2019
Advanced glycation end products (AGE) and receptor for AGE (RAGE) in patients with active tuberculosis

This week we suggest to read an article titled "Advanced glycation end products (AGE) and receptor for AGE (RAGE) in patients with active tuberculosis, and their relationship between food intake and nutritional status", published on the US National Library of Medicine- National Institutes of Health website.


Tuberculosis (TB), caused by Mycobacterium tuberculosis complex, is a major public health problem worldwide, especially in low- and middle-income countries. It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis, and 8 million develop the active form of the disease each year, resulting in 2 million deaths per year. Brazil is in 18th place among the 22 countries responsible for 80% of TB cases globally.

The pathogenesis of the consumptive syndrome, which is long recognized as a characteristic of TB, is largely unknown. The proinflammatory cytokines are the initial candidates as agents causing the metabolic alterations. In addition, cell-mediated immunity and innate immune responses play an important role.

The receptor for advanced glycation end products (RAGE), a pattern-recognition receptor that binds multiple ligands, is expressed in normal lungs and is upregulated during inflammation and infection. AGEs are a heterogeneous group of irreversible products resulting from nonenzymatic glycation between reducing sugars and free amino groups of proteins, nucleic acids, or lipid; carboxymethyl lysine (CML) is the predominant AGE in human plasma, which is over synthesized in conditions of inflammation and lung damage. The interaction between AGEs and RAGE on the plasma membrane causes inflammation, oxidative stress, and apoptosis in lung cells.

Studies investigating the relationship between food intake, nutritional status, AGE and RAGE levels and TB, are mostly with animal models.

The authors reported the results of a prospective case-control (1:1), pilot study, conducted in a general, tertiary care, university-affiliated hospital (Hospital de Clı´nicas de Porto Alegre–HCPA), from June 2017 to June 2018, evaluating AGEs and RAGE levels in adult patients with active TB and healthy controls, and investigating the relationship between food intake and nutritional status with AGEs and RAGE levels.

35 TB patients and 35 controls were enrolled. Demographic data, presence of cough, fever, night sweating, hemoptysis, sputum production, weight loss, dyspnea, chest pain, smoking status, alcohol consumption, drug use, presence of comorbidities, results of the main diagnostic tests, outcome of hospitalization were recorded. Blood sample was collected after an overnight fast.

The authors found that sRAGE levels were higher in TB patients than in controls (p = 0.046). In contrast, only among cases that were current smokers, lower sRAGE levels were associated with weight loss and mortality (p = 0.006). Body Mass Index (BMI) was significantly lower in cases than in controls (p < 0.0001). Also, undernutrition was more frequent in cases than in controls. However, there was no significant correlation between those parameters and CML or sRAGE levels. There was no statistically significant difference in CML levels between cases and controls.

The authors concluded highlighting that, although some limitations (it was a single center study, the higher prevalence of HIV among cases could have been a confounding factor, the US common diets used could be different from the Brailian diet), this was the first study, which generates a hypothesis on the role of CML/RAGE in TB patients and not in animal models.

Click here to read more.

 AUTHORS: Andrades M, Coutinho SE, de Almeida EGC, Holler SR, Silva DR, Silva LF, Skupien EC, Lazzari TK, Zampieri LR.