Amyloid deposition in granuloma of tuberculosis patients: A single-center pilot study

The formation of granuloma is one of the characteristic features of tuberculosis. Besides, elevated serum amyloid A (SAA) protein level is the indicator for chronic inflammation associated with tuberculosis. The linkage between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid onset and deposition start sites are not well understood in tuberculosis. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of SAA protein and proteases, cleaving SAA into aggregation-prone fragments. 150 tuberculosis patients were identified and biopsies were collected from the affected organs. Patients showing eosinophilic hyaline-rich deposits within granuloma and its periphery were further screened for the presence of amyloid deposits. Upon Congo red staining, these hyaline deposits exhibited characteristic apple-green birefringence under polarized light, confirming their amyloid nature in 20 patients. Further upon Immuno-histochemical staining with anti-SAA antibody, the amyloid enriched areas showed positive immunoreactivity. In this pilot study, we have shown granuloma as a potential site for serum amyloid A derived amyloid deposition in tuberculosis patients. This study would expand the clinical and fundamental research for understanding the mechanism of amyloid formation in granuloma underlying tuberculosis and other chronic inflammatory conditions.