03499nas a2200409   4500000000100000008004100001653002100042100001300063700001100076700001400087700002300101700001400124700001200138700001400150700001800164700001200182700001300194700001200207700001000219700001400229700001300243700001500256700001300271700001400284700001300298700001500311700001200326700001700338700001200355700001200367245010400379856008800483300000800571490000700579520248900586022001403075       2015                            d10aImmune-profiling1 aKhadge S1 aBanu S1 aBobosha K1 aPloeg-van Schip JJ1 aGoulart I1 aThapa P1 aKunwar CB1 aMeijgaarden K1 aEeden S1 aWilson L1 aKabir S1 aDey H1 aGoulart L1 aLobato J1 aCarvalho W1 aBekele Y1 aFranken K1 aAseffa A1 aSpencer JS1 aOskam L1 aOtttenhoff T1 aHagge D1 aGeluk A00aLongitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625471/pdf/12879_2015_Article_1128.pdf  a4770 v153 a<p><strong>Editor's Abstract: </strong></p>

<p>BACKGROUND:<strong> </strong>Acute inflammatory reactions are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. In leprosy, an infectious disease initiated by Mycobacterium leprae (M. leprae), these reactions represent the major cause of permanent neuropathy. However, laboratory tests for early diagnosis of reactional episodes which would significantly contribute to prevention of tissue damage are not yet available. Although classical diagnostics involve a variety of tests, current research utilizes limited approaches for biomarker identification. In this study, we therefore studied leprosy as a model to identify biomarkers specific for inflammatory reactional episodes.</p>

<p>METHODS: To identify host biomarker profiles associated with early onset of type 1 leprosy reactions, prospective cohorts including leprosy patients with and without reactions were recruited in Bangladesh, Brazil, Ethiopia and Nepal. The presence of multiple cyto-/chemokines induced by M. leprae antigen stimulation of peripheral blood mononuclear cells as well as the levels of antibodies directed against M. leprae-specific antigens in sera, were measured longitudinally in patients.</p>

<p>RESULTS:<strong> </strong>At all sites, longitudinal analyses showed that IFN-γ-, IP-10-, IL-17- and VEGF-production by M. leprae (antigen)-stimulated PBMC peaked at diagnosis of type 1 reactions, compared to when reactions were absent. In contrast, IL-10 production decreased during type 1 reaction while increasing after treatment. Thus, ratios of these pro-inflammatory cytokines versus IL-10 provide useful tools for early diagnosing type 1 reactions and evaluating treatment. Of further importance for rapid diagnosis, circulating IP-10 in sera were significantly increased during type 1 reactions. On the other hand, humoral immunity, characterized by M. leprae-specific antibody detection, did not identify onset of type 1 reactions, but allowed treatment monitoring instead.</p>

<p>CONCLUSIONS:<strong> </strong>This study identifies immune-profiles as promising host biomarkers for detecting intra-individual changes during acute inflammation in leprosy, also providing an approach for other chronic (infectious) diseases to help early diagnose these episodes and contribute to timely treatment and prevention of tissue damage.</p>
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