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10.1136/annrheumdis-2015-208140 http://scihub22266oqcxt.onion/10.1136/annrheumdis-2015-208140 C4959992!4959992!27088255     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27088255&cmd=llinks): Failed to open stream: HTTP request failed! 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Altered Type II Interferon Precedes Autoantibody Accrual and Elevated Type I Interferon Activity Prior to Systemic Lupus Erythematosus Classification |pdf=|usr=}}{{27088255}} gab.com Text Altered Type II Interferon Precedes Autoantibody Accrual and Elevated Type I Interferon Activity Prior to Systemic Lupus Erythematosus Classification JO: Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=27088255 #FOAvip Objectives: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-?) activity, and IFN-associated soluble mediators to disease development leading to SLE. Methods: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan = 4.3 years) and unaffected healthy controls matched by age (± 5 years), gender, race, and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-? activity, IFN-associated mediators, and autoantibodies were evaluated and temporal relationships assessed by growth curve modeling, path analysis, Analysis of Covariance, and random forest models. Results: In cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-? activity in growth curve models, with elevated IFN-? activity and BLyS levels occurring shortly before SLE classification (p?0.005). Cases were distinguished by multivariate random forest models incorporating IFN-?, MCP-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% > 4 years pre-classification; 97% within 2 years of SLE classification). Conclusions: Years before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-? activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials. Twit Text FOAVip Altered Type II Interferon Precedes Autoantibody Accrual and Elevated Type I Interferon Activity Prior to Systemic Lupus Erythematosus Classification ????Ann Rheum Dis http://www.kidney.de/pget.php?&tw=1&pmid=27088255 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27088255 #FOAvip English Wikipedia <ref>{{Cite pmid|27088255}}</ref> Altered Type II Interferon Precedes Autoantibody Accrual and Elevated Type I Interferon Activity Prior to Systemic Lupus Erythematosus Classification #MMPMID27088255 Munroe ME; Lu R; Zhao YD; Fife DA; Robertson JM; Guthridge JM; Niewold TB; Tsokos GC; Keith MP; Harley JB; James JA Ann Rheum Dis 2016[Nov]; 75 (11): 2014-21 PMID27088255show ga Objectives: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-?) activity, and IFN-associated soluble mediators to disease development leading to SLE. Methods: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan = 4.3 years) and unaffected healthy controls matched by age (± 5 years), gender, race, and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-? activity, IFN-associated mediators, and autoantibodies were evaluated and temporal relationships assessed by growth curve modeling, path analysis, Analysis of Covariance, and random forest models. Results: In cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-? activity in growth curve models, with elevated IFN-? activity and BLyS levels occurring shortly before SLE classification (p?0.005). Cases were distinguished by multivariate random forest models incorporating IFN-?, MCP-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% > 4 years pre-classification; 97% within 2 years of SLE classification). Conclusions: Years before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-? activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials. äAltered Type II Interferon Precedes Autoantibody Accrual and Elevated (epmc).pdf DeepDyve Pubget Overpricing