Paradoxical reactions in patients with tuberculous lymphadenitis: A pilot immunopathogenic study.

OBJECTIVES

Paradoxical reactions (PRs) in HIV-negative tuberculosis is not well understood. This study aimed to determine the incidence and clinical and immunological predictors of PRs.

METHODS

Patients with tuberculous lymphadenitis on anti-tuberculous therapy were monitored for PR. Clinical, histopathological, microbiological, and immunological parameters of PR (n = 10) and no PR (n = 66) groups were analyzed at baseline, 2 months, and 6 months. Peripheral blood mononuclear cells from patients with PR (n = 9) and no PR (n = 13) were stimulated with TB-ESAT peptide, and messenger RNA (mRNA) expressions of cytokines (interleukin [IL]-4, IL-10, IL-12, tumor necrosis factor [TNF]-α, interferon [IFN]-γ), and transcription factors (T-bet, GATA-3) were quantified.

RESULTS

PR incidence was 5.7% (four of 70); six patients presented with PR at baseline. The mean PR onset was 3.25 months. The absence of necrosis at baseline was protective (odds ratio: 0.069; P = 0.039). IL-10 mRNA at 2 months and IL-12 mRNA at 6 months increased in the PR compared with the no PR group (P = 0.05). In the PR group, only baseline T-bet mRNA correlated with IFN-γ (r = 0.79, P <0.01) but TNF-α correlated at baseline and 2 months (r = 0.97, P <0.000; r = 0.86, P <0.002). In the no PR group, T-bet mRNA correlated with IFN-γ and TNF-α at all time points (P <0.05), whereas GATA-3 mRNA correlated with IL-4 and IL-10 at 2 and 6 months (P <0.05).

CONCLUSION

Differential Th1/Th2 regulation driven by transcriptional factors alters cytokine expression, influencing PR. Further transcriptomic/proteomic studies are needed to elucidate immune mechanisms.