Complement component 3c and tumor necrosis factor-α systemic assessment after Candida antigen immunotherapy in cutaneous warts



Cutaneous warts are the commonest benign lesion produced by human papillomavirus. Lesions often regress spontaneously yet have a high rate of recurrence. They impair patients’ quality of life and carry the potential risk of cancer. Nowadays, Candida antigen immunotherapy has become an encouraging therapeutic modality for warts. We tried to assess the role of the complement pathway and T helper 1 immune response in clinical response to Candida antigen immunotherapy via complement component 3c (C3c) and tumor necrosis factor (TNF)-α, respectively.


A total of 44 patients with cutaneous warts were enrolled in the study. Patients were injected with Candida antigen at 2-week interval until complete clearance of the lesion or for a maximum of 5 sessions. Blood samples were collected before initiation and after completion of immunotherapy. C3 and C4 were measured using an automated turbidimetric method. Mannose-binding lectin (MBL), C3c, and TNF-α were measured using enzyme-linked immune sorbent assay.


A total of 56.4%, 17.9%, and 25.7% of the patients showed complete, partial, and no response to immunotherapy, respectively. Lesions on the dorsum of the foot and sole showed significant clearance (p value = 0.037). All patients had no deficient C3, C4, and MBL serum levels. C3c and TNF-α serum levels were significantly higher in non-responder group (p value < 0.001 and < 0.001, respectively). C3c and TNF-α serum levels were strongly correlated in all the studied patients (r = 0.8, p value < 0.001).


Candida antigen immunotherapy is an effective therapeutic modality for cutaneous warts. C3c and TNF-α serum levels were higher in patients who failed to respond to immunotherapy.

Clinical trial registry number

NCT04399577, May 2020 “retrospectively registered”

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.


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We are grateful to the patients and their families for their cooperation with the trial.

Author information




All the named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Corresponding author

Correspondence to Noha M. Hammad.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki of 1964 and in compliance with clinical practices and local regulatory requirements. This study was approved by the institutional review board (IRB) Zagazig University Faculty of Medicine. Prior to enrollment, written informed consent was obtained from competent adult patients and from the legal representatives of patients younger than 21 years of age.

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Fig. 3

CONSORT flow diagram. A single-arm, open-label clinical trial evaluating disease response following treatment with Candida antigen immunotherapy in patients with cutaneous warts

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Hammad, N.M., Abdelhadi, A.A., Fawzy, M.M. et al. Complement component 3c and tumor necrosis factor-α systemic assessment after Candida antigen immunotherapy in cutaneous warts. Braz J Microbiol (2020).

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  • Candida antigen
  • Complement component 3c
  • Immunotherapy
  • Tumor necrosis factor-α
  • Warts