Ocular Tuberculosis: A Clinicopathologic and Molecular Study

Wroblewski, Keith J.; Hidayat, Ahmed A.; Neafie, Ron; Rao, Narsing A.; Zapor, Michael

doi:10.1016/j.ophtha.2010.08.011

Cited by 125 publications

(80 citation statements)

References 19 publications

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“…3 The few histopathologic studies that are available for ocular TB have confirmed presence of Mycobacterium tuberculosis (Mtb) in ocular tissues and highlighted the extreme paucibacillary nature of this infection. 6 An animal model of ocular TB in aerosol-infected guinea pigs has demonstrated the development of ocular lesions from lung infection, although it provides limited information on immune mechanisms in human disease. 7 Despite these developments, several clinical observations that are crucial to the diagnosis and management of TBU remain unexplained.…”

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confidence: 99%

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Tagirasa

Parmar

Barik

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular Tcell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. METHODS. We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-c, TNF-a, and IL-17 and analyzed on flow cytometry. Antigenic specificity was determined by activating with Mycobacterium tuberculosis-specific antigen Early Secreted Antigenic Target-6 (ESAT-6) or retinal crude extract (RCE). Activation-induced cell death (AICD) characteristics of each T-cell population were analyzed by staining for PI-Annexin V, Fas-FasL, phospho-Akt, and phospho-Erk1/2. RESULTS. Immunophenotyping of vitreous humor samples demonstrated polyfunctional effector and central memory CD4þ T helper cells coexpressing IFN-c, TNF-a, and IL-17. Both ESAT-6 and RCE (autoreactive) specificity was found in T cells extracted from TBU samples; however, the mycobacterial and autoreactive T-cell populations differed in their sensitivity to AICD. Autoreactive T cells appeared to resist AICD through decreased expression of apoptotic markers, FasL and caspase-3, sustained phosphorylation of Akt, and lowered Erk1/2 activity.CONCLUSIONS. Autoreactive T cells are present in TBU eyes and are relatively resistant to AICD. An understanding of this epiphenomenon could be crucial in planning treatment of TBU patients, and interpreting response to anti-TB therapy.

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confidence: 99%

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Tagirasa

Parmar

Barik

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…This corroborates with a report of 42 histopathologically proven ocular TB cases, in which 40% had negative TST and 57% had normal chest x-ray wherever reports were available. 21 Herpes viruses (HSV, VZV, and CMV) have been reported to cause immune-mediated choroiditis, both in clinical and histological studies. [22][23] Priya et al investigated the presence of herpes viruses (including CMV) in TST-negative patients with serpiginous choroiditis with conventional virological methods and PCR.…”

Section: Discussionmentioning

confidence: 99%

Polymerase Chain Reaction Evaluation of Infectious Multifocal Serpiginoid Choroiditis

Mohan¹,

Balne

Panda³

et al. 2014

Ocular Immunology and Inflammation

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“…Current evidence shows that while TST is more sensitive [ 278 ], QFT and T-SPOT are more specifi c for the diagnosis of presumed ocular tuberculosis ( [ 11 , 12 ], EBM: C, 2+). TST and T-SPOT test should be the investigation of choice in high and low endemic populations, respectively ( [ 12 ], EBM:C, 2+).…”

Section: Diagnosismentioning

confidence: 99%