Evaluation of Potential Antigen-specific Host Biomarkers in QuantiFERON Supernatants as Candidates for the Diagnosis of Ocular Tuberculosis.

Purpose: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB).Methods: We investigated 47 host markers in QuantiFERON supernatants from 92 individuals with uveitis using the Luminex platform. We evaluated the potential of individual and combined biomarkers to distinguish between patients with possible, probable, and no OTB.Results: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1ß, in individuals with OTB versus no OTB regardless of HIV status. Individuals with probable and possible OTB only differed regarding GM-CSF. We identified a four-marker biosignature (CD40 L, IL-33, IFN-γ, and SAP) which diagnosed OTB with an area under the ROC curve of 0.80, sensitivity = 56.3% and specificity = 90.0%.Conclusion: This represents the first attempt at screening QuantiFERON supernatants for biomarkers to diagnose OTB. We identified candidate biosignatures which may aid in diagnosing OTB in both HIV positive and negative patients.

Longitudinal analysis of serum cytokine profile among patients with tubercular multifocal serpiginoid choroiditis: a pilot study.

PURPOSE: To analyze the serum cytokines profile in patients with tubercular multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy (ATT) and oral corticosteroids. METHODS: In this prospective longitudinal study, patients with active TB MSC were included. Serum levels of interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α were analyzed using bead-based immunoassay. The levels of transforming growth factor (TGF)-ß were measured using cytokine bead array. Serial measurement was performed at baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing paradoxical worsening (PW) of TB MSC were identified and their serum levels of cytokines were compared with those patients who showed healing of lesions. Comparison of cytokine levels with baseline values was also performed. RESULTS: Twelve patients (three females) were included in the study. Four patients showed paradoxical worsening of TB MSC at 3.2 ± 1 weeks after initiation of therapy. Compared to patients who showed healing of lesions, patients with PW showed higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW, levels of IFN-γ peaked at 1 week ((p = 0.01) and levels of TNF-α peaked at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed healing. There was no significant difference in TGF-ß levels at any time point in either group (p > 0.47). CONCLUSIONS: Baseline and serial levels of inflammatory serum cytokines may help in predicting the response to ATT and corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in pro-inflammatory cytokines after initiation of ATT indicating higher bacillary load.

Three years of experience with QuantiFERON-TB gold testing in patients with uveitis.

PURPOSE: Overview of the results of QuantiFERON-TB Gold (QFT) testing on uveitis patients in an interdisciplinary setting for a period of 3 years. METHODS: Database search of all the patients tested for tuberculosis (Tb) with QFT. RESULTS: Of 343 tested patients, overall 80 (23.3%) were positive and 253 (73.8%) negative (results were nonconclusive for 10 patients). Anatomic localization of the patients who tested positive were distributed (% of QFT(+) tests) as anterior n = 12 (15.0%), intermediate n = 22 (27.5%), posterior n = 26 (32.5%), and pan n = 18 (22.5%). In 43 QFT(+) patients we presumed a diagnosis of Tb due to additional clinical findings. Of these patients 16 were treated with full therapy following WHO recommendations. CONCLUSIONS: QFT testing gives surprisingly high numbers of positives in uveitis patients. This is not sufficiently explained by immigrant status of the patients. The frequency of positives is substantially higher than in other cohorts. This raises important questions regarding treatment implications.

Utility of QuantiFERON®-TB Gold test in diagnosis and management of suspected tubercular uveitis in India.

The tuberculin skin test, used to detect latent systemic tuberculosis (TB), has its limitations. The utility of interferon-gamma assays, found useful in the diagnosis of latent TB, is still unestablished in tubercular uveitis. We present the results of QuantiFERON(®)-TB Gold (QFT-G) test and its relevance in the diagnosis and management of suspected tubercular uveitis in India. All suspected tubercular uveitis patients seen at our uveitis clinic between October 2006 and June 2008 who underwent relevant blood investigations, chest X-rays, Mantoux tests and QFT-G tests were included. Clinical profile, systemic correlation and outcome with treatment were analysed. Fifty suspected tubercular uveitis patients underwent QFT-G testing. The age range of the patients was 6-55 years (mean 32.66 years). Seven patients presented with active and three with a past history of systemic TB. The QFT-G test was positive in 29 patients. Radiological findings of TB were seen in four patients with a positive QFT-G and one patient with a negative QFT-G test. In 11 patients both QFT-G and Mantoux tests were positive. Eighteen Mantoux-negative patients were QFT-G-positive. Significantly, no patient with a positive Mantoux had a negative QFT-G test. Of the 32 patients with posterior uveitis, 17 patients had serpiginous choroiditis, four patients had a choroidal granuloma, six patients had multifocal choroiditis, four patients had retinal vasculitis, and one patient had a subretinal abscess. All QFT-G-positive patients were treated with anti-tuberculosis therapy as well as systemic steroids with a favorable clinical outcome. Our study shows that the QFT-G test is very useful in the diagnosis and management of suspected ocular TB. It was found to be very sensitive in identifying latent TB patients who, upon treatment, had a significantly reduced frequency of recurrences. It was more sensitive than the Mantoux test and is not significantly affected by previous treatment with systemic steroids or immunosuppressives. A negative QFT-G test can also be used as an adjunct before initiation of systemic steroids or immunosuppressives in uveitic patients particularly in an endemic setting like India.

QuantiFERON-TB gold cut-off value: implications for the management of tuberculosis-related ocular inflammation.

PURPOSE: To evaluate the accuracy of QuantiFERON-TB Gold testing in patients with presumptive tuberculosis-ocular inflammation. DESIGN: Prospective nonrandomized case series and clinical laboratory investigation. METHODS: Ninety-six consecutive patients presenting with ocular inflammation between January and October 2007 were tested using QuantiFERON-TB Gold. Positive patients received a 6-month anti-tuberculosis treatment. Patient follow-up ranged from 12 months to 24 months. Treatment was considered effective at the end of follow-up, in cases of no or a 2-point decrease of ocular inflammation (SUN criteria) and systemic corticosteroids stopped or tapered to 10 mg/day. RESULTS: Mean age was 51 ± 17 years. Types of ocular inflammation included scleritis (n = 7), panuveitis (n = 34), and posterior (n = 15), intermediate (n = 14), and anterior uveitis (n = 15). QuantiFERON-TB Gold was positive in 42 cases (44%), negative in 51 cases (53%), and undetermined in 3 cases (3%). Among positive QuantiFERON-TB Gold patients, 25 received a full anti-tuberculosis treatment, which was effective in 15 cases (60%). Associated systemic steroids were given to 6 patients and tapered to 10 mg/day or less in all cases. Median QuantiFERON-TB Gold value was significantly higher in the group with a successful therapeutic response (7.67 IU/mL [0.46 to 33.37]) compared to the group with treatment failure (1.22 IU/mL [0.61 to 4.4]), P = .026. CONCLUSION: Results of anti-tuberculosis treatment were encouraging in QuantiFERON-TB Gold-positive ocular inflammation, especially with values over 2 IU/mL in our study, suggesting that a higher cut-off value than that given by the manufacturer should be considered to better identify ocular inflammation that can benefit from full anti-tuberculosis treatment.

[Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay]. / Diagnostic des uvéites tuberculeuses: intérêt des tests interférons gamma.

M. tuberculosis is a possible cause of uveitis; the diagnosis is often difficult. The aim of this study is to evaluate, in this context, the application of an interferon gamma assay, the SpotTB™. The prospective study, in patients presenting with uveitis without obvious cause and not resolving with local treatment, compared the therapeutic approach (giving antituberculous treatment or not) with and without the result of the SpotTB™. The analyses included 23 patients: 78% had received BCG; 78% had isolated ocular involvement; 22% had associated mediastinal lymphadenopathy. The results of the IDR and the SpotTB™ were concordant in 61%, discordant in 22% and non-evaluable in 17% of cases. In the patients with isolated ocular involvement the SpotTB™ avoided treatment in five and reinforced the decision not to treat in 13 others. In the patients with mediastinal lymphadenopathy, the SpotTB™ reinforced the diagnosis of sarcoidosis in four cases (one lost from view). In conclusion, when infection with M. tuberculosis is considered in the aetiology of uveitis the SpotTB™ allows, in a significant number of cases, the avoidance of antituberculous treatment.

Utility of QuantiFERON TB gold test in a south Indian patient population of ocular inflammation.

AIM: To study the utility of interferon-g release assays (QuantiFERON TB gold test) in a south Indian patient population of intraocular inflammation. DESIGN: Evaluation of a diagnostic test- a pilot study from January 2007 to October 2008. MATERIALS AND METHODS: QuantiFERON TB gold test was performed on the following groups of patients following an informed consent. Group A included healthy volunteers without any exposure to tuberculosis (TB) or past history of TB (n=22). Group B included patients with active systemic TB diagnosed by the demonstration of acid-fast bacilli or by the histopathology finding of caseation with granuloma formation from the sputum, lymph node, skin or intestinal biopsies (n=26). Group C included patients with uveitis of known etiologies other than intraocular TB without any history of exposure to active TB (n=21). Group D included patients with a diagnosis of presumed intraocular TB, who responded to antitubercular therapy by decreased or no recurrences following treatment and with a minimum of nine months follow-up following initiation of antitubercular therapy (n=39). RESULTS: The sensitivity and specificity of the QuantiFERON TB gold test to pick up active systemic TB was 58% and 77% respectively. The sensitivity and specificity of the QuantiFERON TB gold test to pickup intraocular TB was 82% and 76% respectively. CONCLUSIONS: QuantiFERON TB gold test alone may not be specific for intraocular TB. The significance of this test in a case scenario needs to be interpreted with clinical presentation and other evidences for intraocular TB.

Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay.

PURPOSE: To determine the role of the QuantiFERON-TB Gold In-Tube (QFT) (Cellestis Inc., Carnegie, Australia) assay in the diagnosis of tuberculosis (TB) uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: The study included 157 patients with suspected TB uveitis seen over an 18-month period (August 1, 2006, to February 31, 2007) at the Singapore National Eye Center (SNEC) uveitis clinic. METHODS: We identified all cases of suspected TB uveitis in the above-mentioned time period and reviewed all medical records of the cases. Clinical findings, type of treatment instituted, response to treatment, and results of investigations such as QFT, tuberculin skin test (TST), and chest x-rays were recorded. A novel method of using treatment response to determine the presumed diagnosis of TB was used to estimate the accuracy of QFT and TST. MAIN OUTCOME MEASURES: The positive likelihood ratio (LR+), negative likelihood ratio (LR-), and area under the receiver operator characteristic curve (ROC) of the investigations were estimated. RESULTS: QFT is not superior to the TST in sensitivity as a screening test or first-line study in TB-related uveitis; however, QFT is more specific than the TST in identifying infections by Mycobacterium tuberculosis. Negative QFT tests should be interpreted with caution, because they do not exclude the diagnosis. CONCLUSIONS: The new QFT is only slightly superior to the TST in the diagnosis of TB uveitis. Thus, there is an important role for interpreting the QFT together with the TST. This is the first and largest study of its kind to evaluate the use of QFT in the clinical diagnosis of TB uveitis.

[In vitro measurement of whole blood gamma interferon as a diagnostic tool in primary ocular tuberculosis]. / Dosage plasmatique de l'interféron gamma comme moyen diagnostique en cas de tuberculose oculaire isolée.

Tuberculosis (infection by Mycobacterium tuberculosis) remains a public health problem with increasing incidence. The diagnosis of primary ocular tuberculosis is troublesome because of the low sensitivity and poor specifity of routine diagnostic methods and the problems obtaining reliable samples. We report the cases of two patients, one immunocompromised male and one immunocompetent male, presenting chorioretinitis with high clinical suspicion of ocular tuberculosis. We performed serologies, polymerase chain reaction tests in aqueous humor, a purified protein derivative skin test, and measurement of interferon-gamma in whole blood using the QuantiFERON-TB Gold assay. The QuantiFERON-TB Gold assay was positive in both cases, in agreement with the diagnosis of ocular tuberculosis. The purified protein derivative skin test was positive in one case. The whole blood interferon-gamma assay is a precious tool for detecting extrapulmonary tuberculosis, especially in cases of primary ocular disease.

[Determining the level of malondialdehyde in patients with different types of tuberculous uveitis]. / Opredelenie malonovogo dial'degida u bol'nykh s razlichnym tipom techeniia tuberkuleznogo uveita.

A clinical follow-up of 52 tuberculous uveitis patients showed that the choice of an appropriate plan of pathogenetic treatment and prognosis of the disease outcome requires differentiation of types of a tuberculous process in the eye. A new method has been suggested for determining the type of the tuberculous uveitis course by studying changes in the blood content of malonic dialdehyde (increase, decrease or absence of changes).