Uveitis with occult choroiditis due to Mycobacterium kansasii: limitations of interferon-gamma release assay (IGRA) tests (case report and mini-review on ocular non-tuberculous mycobacteria and IGRA cross-reactivity)

Ocular tuberculosis is difficult to diagnose but should be suspected when uveitis fails to respond to inflammation suppressive therapy. Interferon-gamma release assays (IGRAs) represent a substantial help to diagnose suspected ocular tuberculosis especially in non-endemic areas. Indocyanine green angiography (ICGA) is able to detect clinically silent choroiditis that, when associated with a positive IGRA test, should lead the clinician to suspect ocular tuberculosis, warranting specific therapy. The fact that IGRA tests can also react with some atypical strains of mycobacteria is not always known. We report here a case with resistant post-operative inflammation that presented with occult ICGA-detected choroiditis and a positive IGRA test that was most probably due to the non-tuberculous mycobacterium (NTM) Mycobacterium kansasii. A 66year-old man presented with a resistant cystoid macular oedema (CMO) in his left eye after combined cataract and epiretinal membrane surgery. At entry, his best-corrected visual acuity (BCVA) was 0.5 for far and near OS. Intraocular inflammation measured by laser flare photometry was elevated in the left eye (54.4ph/ms) and also in the right eye (50.9ph/ms). Four subTenon's injections of 40mg of triamcinolone did not produce any substantial improvement. Therefore a complete uveitis work-up was performed. Fluorescein angiography showed CMO OS and ICGA showed numerous hypofluorescent dots and fuzziness of choroidal vessels in both eyes. Among performed laboratory tests, the QuantiFERON®-TB Gold test was positive. After a pulmonological examination disclosing a right upper lobe infiltrate, the patient was started on a triple anti-tuberculous therapy. Bronchial aspirate, obtained during bronchoscopy, was Ziehl-positive and culture grew M. kansasii. Nine months later, BCVA OS increased to 1.0 and flare decreased to 40.2ph/ms. The CMO OS resolved angiographically and did not recur with a macula still slightly thickened on OCT. Suspected ocular tuberculosis based on clinical findings and a positive IGRA test can, in rare instances, be due to atypical mycobacteria that also produce positive IGRA tests such as M. kansasii, M. szulgai, M. gordonae, M. flavescens and M. marinum. In our case failure to isolate the atypical mycobacterium would not have had negative therapeutic consequences, as M. kansasii is sensitive to the standard anti-tuberculous treatments, which is not the case with other NTM

Eotaxin-1 (CCL11) up-regulation in tears during seasonal allergic conjunctivitis

Purpose: To compare in-season eotaxin-1 levels in tears of patients suffering from seasonal allergic conjunctivitis (SAC) with (1) tears of normal subjects and (2) tears of SAC patients out of season. Methods: Tears of 11 SAC patients and six control volunteers were collected during the pollen season. Tears of five SAC patients showing a strong sensitivity to grass pollen (skin-prick tests and specific serum IgE) were collected both in season and out of season. ELISA measured eotaxin-1 level. Results: Eotaxin-1 concentration in tears of SAC patients [2,100±503 (SEM)pg/ml] and normal subjects (1,193±176pg/ml) were significantly different (P=0.0049). Regarding allergic patients, the clinical score (sum of five allergic criteria) was significantly different in season and out of season (P=0.0043) as was also the case with eotaxin-1 concentration (P=0.024). Conclusions: The eotaxin-1 concentration in tears of patients showing hay fever could confirm a diagnosis of seasonal ocular allerg

Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells

Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an important role in the pathogenesis of atherosclerosis. Moreover, atherosclerotic lesions contain the Th1-type cytokine IFN-gamma, a potentiator of atherosclerosis. The present study demonstrates the differential expression of the 3 IFN-gamma-inducible CXC chemokines--IFN-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha chemoattractant (I-TAC)--by atheroma-associated cells, as well as the expression of their receptor, CXCR3, by all T lymphocytes within human atherosclerotic lesions in situ. Atheroma-associated endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (MO) all expressed IP-10, whereas Mig and I-TAC were mainly expressed in ECs and MO, as detected by double immunofluorescence staining. ECs of microvessels within lesions also expressed abundant I-TAC. In vitro experiments supported these results and showed that IL-1beta, TNF-alpha, and CD40 ligand potentiated IP-10 expression from IFN-gamma-stimulated ECs. In addition, nitric oxide (NO) treatment decreased IFN-gamma induction of IP-10. Our findings suggest that the differential expression of IP-10, Mig, and I-TAC by atheroma-associated cells plays a role in the recruitment and retention of activated T lymphocytes observed within vascular wall lesions during atherogenesis

CD4+CD25−mTGFβ+ T cells induced by nasal application of ovalbumin transfer tolerance in a therapeutic model of asthma

Background: Intranasal administration of high amount of allergen was shown to induce tolerance and to reverse the allergic phenotype. However, mechanisms of tolerance induction via the mucosal route are still unclear. Objectives: To characterize the therapeutic effects of intranasal application of ovalbumin (OVA) in a mouse model of bronchial inflammation as well as the cellular and molecular mechanisms leading to protection upon re-exposure to allergen. Methods: After induction of bronchial inflammation, mice were treated intranasally with OVA and re-exposed to OVA aerosols 10 days later. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. The respective role of CD4+CD25+ and CD4+CD25− T cells in the induction of tolerance was analysed. Results: Intranasal treatment with OVA drastically reduced inflammatory cell recruitment into BALF and bronchial hyperresponsiveness upon re-exposure to allergen. Both OVA- specific-proliferation of T cells, Th1 and Th2 cytokine production from lung and bronchial lymph nodes were inhibited. Transfer of CD4+CD25− T cells, which strongly expressed membrane-bound transforming growth factor β (mTGFβ), from tolerized mice protected asthmatic recipient mice from subsequent aerosol challenges. The presence of CD4+CD25+(Foxp3+) T cells during the process of tolerization was indispensable to CD4+CD25− T cells to acquire regulatory properties. Whereas the presence of IL-10 appeared dispensable in this model, the suppression of CD4+CD25−mTGFβ+ T cells in transfer experiments significantly impaired the down-regulation of airways inflammation. Conclusion: Nasal application of OVA in established asthma led to the induction of CD4+CD25−mTGFβ+ T cells with regulatory properties, able to confer protection upon allergen re-exposur