TY - JOUR
T1 - Type I interferon as a biomarker in autoimmunity and viral infection
T2 - a leukocyte subset-specific analysis unveils hidden diagnostic options
AU - Strauß, Romy
AU - Rose, Thomas
AU - Flint, Shaun M.
AU - Klotsche, Jens
AU - Häupl, Thomas
AU - Peck-Radosavljevic, Markus
AU - Yoshida, Taketoshi
AU - Kyogoku, Chieko
AU - Flechsig, Alexandra
AU - Becker, Amy M.
AU - Dao, Kathryn H.
AU - Radbruch, Andreas
AU - Burmester, Gerd Rüdiger
AU - Lyons, Paul A.
AU - Davis, Laurie S.
AU - Hiepe, Falk
AU - Grützkau, Andreas
AU - Biesen, Robert
N1 - Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Abstract: Interferon alpha and its surrogates, including IP-10 and SIGLEC1, paralleled changes of disease activity in systemic lupus erythematosus (SLE). However, the whole blood interferon signature (WBIFNS)—the current standard for type I IFN assessment in SLE—does not correlate with SLE disease activity in individual patients over time. The underlying causes for this apparent contradiction have not been convincingly demonstrated. Using a multicenter dataset of gene expression data from leukocyte subsets in SLE, we identify distinctive subset-specific contributions to the WBIFNS. In a subsequent analysis, the effects of type I interferon on cellular blood composition in patients with SLE and hepatitis B were also studied over time. We found that type I interferon mediates significant alterations in whole blood composition, including a neutropenia and relative lymphocytosis. Given different effects of type 1 interferon on different leukocyte subsets, these shifts confound measurement of a type 1 interferon signature in whole blood. To minimize and overcome these limitations of the WBIFNS, we suggest to measure IFN-induced transcripts or proteins in a specific leukocyte subset to improve clinical impact of interferon biomarkers. Key messages: Myeloid cells contribute more to the WBIFNS in SLE than their lymphocytic counterpart.Very similar leukocyte subsets reveal distinctive IFN signatures.IFN alpha mixes up composition of blood and leads to a preferential neutropenia, yielding relative lymphocytosis.
AB - Abstract: Interferon alpha and its surrogates, including IP-10 and SIGLEC1, paralleled changes of disease activity in systemic lupus erythematosus (SLE). However, the whole blood interferon signature (WBIFNS)—the current standard for type I IFN assessment in SLE—does not correlate with SLE disease activity in individual patients over time. The underlying causes for this apparent contradiction have not been convincingly demonstrated. Using a multicenter dataset of gene expression data from leukocyte subsets in SLE, we identify distinctive subset-specific contributions to the WBIFNS. In a subsequent analysis, the effects of type I interferon on cellular blood composition in patients with SLE and hepatitis B were also studied over time. We found that type I interferon mediates significant alterations in whole blood composition, including a neutropenia and relative lymphocytosis. Given different effects of type 1 interferon on different leukocyte subsets, these shifts confound measurement of a type 1 interferon signature in whole blood. To minimize and overcome these limitations of the WBIFNS, we suggest to measure IFN-induced transcripts or proteins in a specific leukocyte subset to improve clinical impact of interferon biomarkers. Key messages: Myeloid cells contribute more to the WBIFNS in SLE than their lymphocytic counterpart.Very similar leukocyte subsets reveal distinctive IFN signatures.IFN alpha mixes up composition of blood and leads to a preferential neutropenia, yielding relative lymphocytosis.
KW - Biomarker
KW - Disease activity
KW - Systemic lupus erythematosus
KW - Type I interferon
UR - http://www.scopus.com/inward/record.url?scp=85016428254&partnerID=8YFLogxK
U2 - 10.1007/s00109-017-1515-7
DO - 10.1007/s00109-017-1515-7
M3 - 学術論文
C2 - 28357476
AN - SCOPUS:85016428254
SN - 0946-2716
VL - 95
SP - 753
EP - 765
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 7
ER -
