Sarcoidosis and Tuberculosis Cytokine Profiles: Indistinguishable in Bronchoalveolar Lavage but Different in Blood

Abstract

BackgroundThe clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them.MethodsWe analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples.ResultsWe found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%).ConclusionsThese data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.

Anergic Pulmonary Tuberculosis Is Associated with Contraction of the Vd2+T Cell Population, Apoptosis and Enhanced Inhibitory Cytokine Production

“…On the other hand, Vδ2 + T cells can also suppress host immunity against infections through the secretion of IL-4, IL-10 and other cytokines, thus avoiding overactive immune responses that may lead to the development of pathological lesions [20]. Consistent with a previous study by Thillai et al, our results revealed that the levels of IL-4 and IL-10 in the peripheral blood of tuberculosis patients were markedly higher than in healthy control participants [21]; however, in their measurements they did not distinguish between anergic and TST-positive tuberculosis patients. It has been shown that the level of IL-4 secretion is related to tuberculosis pathogenesis and host immune homeostasis [20].…”

Mathematical model of sarcoidosis

“…However, the source of inflammation in TB arises from the TB antigen (i.e., the Mycobacterium tuberculosis); hence some of the model parameters will have to be changed in the TB case, leading to different conclusions. Indeed, BAL measurements in pulmonary sarcoidosis and pulmonary TB show differences in the expression of cytokines (44,45). Big differences may occur when some of the cytokines are overexpressed or underexpressed.…”

Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis

“…The multiplex cytokine analysis was performed using pre-coated 96 well plates (Human Pro-inflammatory I Ultrasensitive Assay, Meso Scale Discovery–MSD, Maryland, USA) according to the manufacturer instructions and as previously described [12]. 25 μL of the supernatant derived from PBMC incubation with antigen (with PHA ensuring PBMC viability as a positive control) was added per well and samples measured in duplicate.…”