Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response

Background: We aimed to assess the plasma levels of ferritin, C-reactive protein (CRP), and adenosine deaminase (ADA) at baseline and their utility as biomarkers to monitor response to treatment in extrapulmonary tuberculosis (EPTB) patients.

Methods: Prospective measurements of ferritin, CRP, and ADA were done in unstimulated plasma samples of 92 EPTB (49 TB lymphadenitis and 43 TB pleuritis) patients registered for anti-TB treatment. Blood samples were taken at the start, 2, and 6 months of treatment, plasma levels of ferritin and CRP were measured by the enzyme-linked immunosorbent assay and ADA levels by kinetic chemistry method at each time point. Data was analyzed using SPSS version 22. Non-parametric tests were used for paired analysis and two groups' comparison. Spearman's rank test was used for correlation analysis. A Chi-square test was used for categorical variables. A p-value < 0.05 was considered statistically significant.

Results: Before the start of treatment, plasma levels of ferritin were raised in 13% and 45%, CRP in 21% and 64%, and ADA in 70% and 60% of TB lymphadenitis and pleuritis cases respectively. Levels of all three biomarkers with raised values at baseline decreased significantly with treatment at both 2 and 6 months in all patients. [Ferritin (2 months p = 0.001, 6 months p < 0.001), CRP (2 months p < 0.001, 6 months p < 0.001), ADA (2 months p = 0.039, 6 months p < 0.004)]. Plasma levels of ferritin (median 300 ng/ml range = 145-758 ng/ml) and CRP (median 11.73 mg/L, range = 10.45-17.84 mg/L) were significantly higher in TB pleuritis patients, while the levels of ADA were not significantly different among the two groups. Biosignatures generated by different combinations showed that a combination of all three biomarkers could predict treatment response in 83% and 100% of all patients at 2 and 6 months of treatment respectively.

Conclusion: A combination of serum ferritin, CRP, and ADA shows a promising role in monitoring response to treatment in TB lymphadenitis and TB pleuritis patients. Similar studies in larger cohorts are needed to establish a definite role of these biomarkers in EPTB patients.