The expression of TNF-α in recurrent aphthous stomatitis: A systematic review and meta-analysis

Meircurius Dwi Condro Surboyo, Rizky Merdietio Boedi, Ninuk Hariyani, Arvind Babu Rajendra Santosh, Ida Bagus Pramana Putra Manuaba, Pamela Handy Cecilia, I. Gusti Agung Dyah Ambarawati, Adiastuti Endah Parmadiati, Diah Savitri Ernawati

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


Objective: The pathogenesis of recurrent aphthous stomatitis (RAS) is related to an increase of pro-inflammatory cytokine, namely tumor necrosis factor α (TNF-α). This cytokine plays an important role in the development of ulcer lesions, both in saliva, tissues and blood. This systematic review analyzed the differences of TNF-α in lesions, salivary and blood and can be used as a reliable method of diagnosis for RAS. Methods: A comprehensive search of PubMed, Scopus databases, Web of Science, Scielo, Google Scholar and Embase with keywords. The inclusion criteria were studies that assessed the saliva, serum, and RAS lesion, with the outcome reporting the mean of saliva, serum and tissue expression of TNF-α. The risk of bias was also assessed. Result: Healthy individuals showed significantly lower TNF-α than RAS (SMD = -1.517, 95% CI [-2.25, −0.78]). Although there is a significant difference between sample (i.e., saliva, serum) and detection type (i.e., cytometry bead array, ELISA), both methods can detect a significant difference in TNF-α between healthy individuals and RAS patients. Conclusions: The TNF-α is a useful diagnostic marker for RAS. We encourage saliva to detect changes in TNF-α during ulceration as it provides accuracy, reliability, and non-invasive procedure compared to a blood draw.

Original languageEnglish
Article number155946
Publication statusPublished - Sept 2022


  • Recurrent aphthous stomatitis
  • Saliva
  • Serum
  • TNF-α
  • Tissue expression


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