Elsevier

Ophthalmology

Volume 116, Issue 12, December 2009, Pages 2457-2462.e2
Ophthalmology

Original article
Uveitis in a Patient Treated with Bacille-Calmette-Guérin: Possible Antigenic Mimicry of Mycobacterial and Retinal Antigens

https://doi.org/10.1016/j.ophtha.2009.05.021Get rights and content

Purpose

To investigate the cellular immune response in uveitis developing after intravesical Bacille-Calmette-Guérin (BCG) applications.

Design

Experimental study.

Participants

A 72-year-old HLA-B27–negative patient with bilateral granulomatous anterior uveitis that developed during the third cycle of intravesical BCG applications she was receiving for treatment of bladder carcinoma.

Methods

The patient's peripheral T cell reactivity to ocular autoantigens was compared with the response to purified protein derivative (PPD) from Mycobacterium tuberculosis. T-cell proliferation and cytokine and chemokine secretion were measured in vitro.

Main Outcome Measures

Anterior uveitis was treated successfully with topical corticosteroids and cycloplegics.

Results

The following were demonstrated: proliferation to PPD, interphotoreceptor retinoid-binding protein (IRBP), and IRBP-peptide R16, as well as secretion of proinflammatory cytokines in response to PPD, retinal soluble antigen (S-Ag), IRBP, cellular retinal-binding protein (CRALBP), and some S-Ag and IRBP peptides.

Conclusions

These data indicate the generation of a polyclonal autoimmune reaction elicited by BCG. Amino acid sequence alignments revealed homologies between proteins from M. tuberculosis, BCG, and retinal antigens, suggesting antigenic mimicry as a potential cause of uveitis in this patient.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Case Report

A 72-year-old woman was referred by an ophthalmologist to the authors' outpatient department with a bilateral granulomatous anterior uveitis, which had been ongoing for 3 to 4 days. The patient reported painless blurred vision, initially in her left eye. Otherwise, there was no history of previous uveitis. Findings were recorded according to the Standardization of Uveitis Nomenclature criteria. Initially, best-corrected visual acuity was 0.8 in the right eye and 0.6 in the left eye. Both eyes

Peptides and Protein Antigens

Retinal soluble antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP) were prepared from bovine eyes as described,15, 16 and the purity was controlled by gel electrophoresis. Recombinant cellular retinal-binding protein (CRALBP) was obtained and purified as described.17 Chicken ovalbumin (OVA) was obtained from SIGMA (Deisenhofen, Germany), and tuberculin (PPD) and tetanus toxoid (TT) were gifts from Aventis (Marburg, Germany). Custom peptides were purchased from Biotrend

In Vitro Lymphocyte Responses

The patient's lymphocytes were collected when clinical disease had subsided completely. Proliferation exceeding the medium control by 2-fold was observed only for PPD, TT, IRBP, and R16 (Fig 3). Elevated cytokine responses were detected more frequently, revealing T-helper 1 (Th1)-type reactivity with secretion of IFN-γ to all tested retinal antigens and peptides from S-Ag and IRBP as well as to chicken ovalbumin and PPD (Fig 3). Despite the negative tuberculin skin response of the patient, high

Discussion

Bacille Calmette-Guérin instillation is regarded as the most effective treatment and prophylaxis for noninvasive bladder cancer. Live mycobacteria attach to and invade the bladder tumor cells using fibronectin and integrins and induce inflammation with infiltration of macrophages, T and B lymphocytes, and natural killer cells as well as upregulation of proinflammatory cytokines including IL-1, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12, IL-18, IFN-γ, tumor necrosis factor-α, and granulocyte-monocyte

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    Available online: October 7, 2009.

    Manuscript no. 2009-129.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by the German Research Council (DFG), SFB 571 (Projects D3 [GW] and A5 [CAD]).

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