Paradoxical reactions in patients with tuberculous lymphadenitis: A pilot immunopathogenic study
Recommended Citation
Rajendra A, Fletcher JG, Demosthenes JP, Thangavelu P, Ghale BC, Kannangai R, Ramesh MS, Rupali P. Paradoxical reactions in patients with tuberculous lymphadenitis: A pilot immunopathogenic study. Int J Infect Dis. 2026;167:108542.
Document Type
Article
Publication Date
3-19-2026
Publication Title
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Keywords
Cytokines; Mycobacterium tuberculosis; Paradoxical reaction; Th1/Th2 response; Transcription factors; Tuberculous lymphadenitis
Abstract
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.
PubMed ID
41864273
Volume
167
First Page
108542
Last Page
108542
