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O30 Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish SLE patients
  1. Sahwa Elbagir1,
  2. NasrEldeen A Mohammed2,
  3. Vilija Oke3,4,
  4. Anders Larsson5,
  5. Jan Nilsson6,
  6. Amir Elshafie1,7,
  7. Elnour M Elagib8,
  8. Musa AM Nur9,
  9. Iva Gunnarsson3,
  10. Elisabet Svenungsson3 and
  11. Johan Rönnelid1
  1. 1Dept. of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  2. 2Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan
  3. 3Division of Rheumatology, Dept. of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  4. 4Centre for Rheumatology, Academic Specialist centre, Stockholm, Sweden
  5. 5Dept. of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden
  6. 6Dept. of Experimental Medical Science, Lund University, Lund, Sweden
  7. 7Dept. of Clinical Immunology and Transfusion Medicine, Linköping University Hospital, Sweden
  8. 8Rheumatology unit, Military Hospital, Omdurman, Sudan
  9. 9Rheumatology unit, Alribat University Hospital, Khartoum, Sudan

Abstract

Objective In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 Interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines.

Methods We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N=104+192). Autoantibodies targeting ANA-subspecificites: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with Proximity Extension Assay technique or ELISA.

Results Among Sudanese patients, the investigated antibodies significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.

Among Swedish patients for MCP-1, CXCL10, SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared to anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant.

Conclusions In two cohorts of different ethnical origin, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be main drivers of type-1 interferon activity in SLE.

Acknowledgments This work was supported by the Swedish Rheumatism Association (R-932093, to JR, R-840401 to ES); King Gustav Vth 80-year foundation (FAI-2019–0577, to JR, FAI-2019–0628 to ES); the Agnes and Mac Rudberg Foundation; the Signe and Reinhold Sund’s Foundation for Rheumatological Research; the Swedish Society of Medicine and the Ingegerd Johansson Donation (SLS-713911 to ES); the Swedish Research Council (2019–01632, to JR, 2018–02535 to ES); the Uppsala County Council (ALF); the Stockholm County Council (ALF) and the Swedish Heart-Lung Foundation (20170257 and 20190510 to ES).

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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

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