Journal ArticleDOI
Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
Anders A. Bengtsson,Gunnar Sturfelt,Lennart Truedsson,Jonas Blomberg,Gunnar V. Alm,H. Vallin,Lars Rönnblom +6 more
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The close relationship between disease activity in SLE patients and IFN-α serum levels suggests that activation of the type I IFN system might be of importance in the disease process.Abstract:
The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.read more
Citations
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Systematic identification of trans eQTLs as putative drivers of known disease associations
Harm-Jan Westra,Marjolein J. Peters,Tõnu Esko,Hanieh Yaghootkar,Claudia Schurmann,Johannes Kettunen,Mark W. Christiansen,Benjamin P. Fairfax,Katharina Schramm,Joseph E. Powell,Alexandra Zhernakova,Daria V. Zhernakova,Jan H. Veldink,Leonard H. van den Berg,Juha Karjalainen,Sebo Withoff,André G. Uitterlinden,Albert Hofman,Fernando Rivadeneira,Peter A C 't Hoen,Eva Reinmaa,Krista Fischer,Mari Nelis,Lili Milani,David Melzer,Luigi Ferrucci,Andrew B. Singleton,Dena G. Hernandez,Mike A. Nalls,Georg Homuth,Matthias Nauck,Dörte Radke,Uwe Völker,Markus Perola,Veikko Salomaa,Jennifer A. Brody,Astrid Suchy-Dicey,Sina A. Gharib,Daniel A. Enquobahrie,Thomas Lumley,Grant W. Montgomery,Seiko Makino,Holger Prokisch,Christian Herder,Michael Roden,Harald Grallert,Thomas Meitinger,Konstantin Strauch,Yang Li,Ritsert C. Jansen,Peter M. Visscher,Julian C. Knight,Bruce M. Psaty,Samuli Ripatti,Samuli Ripatti,Samuli Ripatti,Alexander Teumer,Timothy M. Frayling,Andres Metspalu,Joyce B. J. van Meurs,Lude Franke +60 more
TL;DR: Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
Journal ArticleDOI
TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITY
TL;DR: The significance of type I interferons (IFN-α/β) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses as mentioned in this paper.
Journal ArticleDOI
Plasmacytoid predendritic cells initiate psoriasis through interferon-α production
Frank O. Nestle,Curdin Conrad,Adrian Tun-Kyi,Bernhard Homey,Michael Gombert,Onur Boyman,Günter Burg,Yong-Jun Liu,Michel Gilliet +8 more
TL;DR: It is suggested that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis and a novel innate immune pathway for triggering a common human autoimmune disease is uncovered.
Journal ArticleDOI
Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus
Franck J. Barrat,Thea Meeker,Josh Gregorio,Jean H. Chan,Satoshi Uematsu,Shizuo Akira,Bonnie Chang,Omar Duramad,Robert L. Coffman +8 more
TL;DR: It is shown that mammalian DNA and RNA, in the form of ICs, are potent self-antigens for TLR9 and TLR7, respectively, and induce IFN-α production by PDCs, suggesting that TLRs may have a critical role in the promotion of lupus through the induction of IFn-α by P DCs.
Journal ArticleDOI
MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins.
Yuanjia Tang,Xiaobing Luo,Huijuan Cui,Xuming Ni,Min Yuan,Yanzhi Guo,Xinfang Huang,Haibo Zhou,Niek de Vries,Paul P. Tak,Shunle Chen,Nan Shen +11 more
TL;DR: Investigation of the contribution of microRNA-146a, identified in the pilot expression profiling step, to the pathogenesis of systemic lupus erythematosus revealed a negative regulator of innate immunity, which provides potential novel strategies for therapeutic intervention.
References
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Journal ArticleDOI
Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.
TL;DR: The development of the SLEDAI is described, a validated model of experienced clinicians' global assessments of disease activity in lupus, which represents the consensus of a group of experts in the field of l upus research.
Journal ArticleDOI
Type I Interferons Keep Activated T Cells Alive
TL;DR: Since IFN-α/β are very efficiently generated in response to viral and bacterial infections, these molecules may be among the signals that the immune system uses to prevent activated T cell death during infections.
Journal ArticleDOI
Selective Expression of an Interleukin-12 Receptor Component by Human T Helper 1 Cells
Lars Rogge,Luisella Barberis-Maino,Mauro Biffi,Nadia Passini,David H. Presky,Ueli Gubler,Francesco Sinigaglia +6 more
TL;DR: The selective expression and regulation of the IL-12R β2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1-Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.
Journal Article
C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes : complement deficiency and systemic lupus erythematosus revisited
Laura C. Korb,J M Ahearn +1 more
TL;DR: It is demonstrated here that when human keratinocytes are rendered apoptotic, they also develop the capacity to specifically and directly bind to C1q in the absence of Ab, which may mediate Ab-independent clearance of apoptotic keratin cells, and prevent immunization with autoantigens of cutaneous origin.
Journal Article
Characteristics of a Soluble Nuclear Antigen Precipitating with Sera of Patients with Systemic Lupus Erythematosus
Eng M. Tan,H. G. Kunkel +1 more
TL;DR: Sera of patients with systemic lupus erythematosus were demonstrated to contain precipitating antibodies to soluble tissue components other than DNA, and one dominant reaction was observed which was provisionally termed the Sm system.