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Two subgroups in sy...
Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjogren's syndrome differ in molecular signatures and treatment perspectives
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- Idborg, Helena (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Zandian, Arash (författare)
- KTH Royal Institute of Technology,KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Dept Prot Sci, SciLifeLab, Div Affin Prote, Stockholm, Sweden
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- Sandberg, Ann-Sofi (författare)
- Karolinska Institutet,Karolinska Institute
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- Nilsson, Bo (författare)
- Uppsala University,Uppsala universitet,Klinisk immunologi
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- Elvin, Kerstin (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Truedsson, Lennart (författare)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Sohrabian, Azita (författare)
- Uppsala University,Uppsala universitet,Klinisk immunologi
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- Rönnelid, Johan (författare)
- Uppsala University,Uppsala universitet,Klinisk immunologi
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- Mo, John (författare)
- AstraZeneca R&D, Patient Safety Resp Inflammat Autoimmun Infect &, Gothenburg, Sweden.
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- Grosso, Giorgia (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Kvarnström, Marika (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Gunnarsson, Iva (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Lehtio, Janne (författare)
- Karolinska Institutet,Karolinska Institute
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- Nilsson, Peter (författare)
- KTH Royal Institute of Technology,KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Dept Prot Sci, SciLifeLab, Div Affin Prote, Stockholm, Sweden
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- Svenungsson, Elisabet (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Jakobsson, Per-Johan (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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(creator_code:org_t)
- 2019-02-18
- 2019
- Engelska.
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1478-6354. ; 21
- Relaterad länk:
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https://arthritis-re...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://lup.lub.lu.s...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BackgroundPrevious studies and own clinical observations of patients with systemic lupus erythematosus (SLE) suggest that SLE harbors distinct immunophenotypes. This heterogeneity might result in differences in response to treatment in different subgroups and obstruct clinical trials. Our aim was to understand how SLE subgroups may differ regarding underlying pathophysiology and characteristic biomarkers.MethodsIn a cross-sectional study, including 378 well-characterized SLE patients and 316 individually matched population controls, we defined subgroups based on the patients' autoantibody profile at inclusion. We selected a core of an antiphospholipid syndrome-like SLE (aPL+ group; positive in the lupus anticoagulant (LA) test and negative for all three of SSA (Ro52 and Ro60) and SSB antibodies) and a Sjogren's syndrome-like SLE (SSA/SSB+ group; positive for all three of SSA (Ro52 and Ro60) and SSB antibodies but negative in the LA test). We applied affinity-based proteomics, targeting 281 proteins, together with well-established clinical biomarkers and complementary immunoassays to explore the difference between the two predefined SLE subgroups.ResultsThe aPL+ group comprised 66 and the SSA/SSB+ group 63 patients. The protein with the highest prediction power (receiver operating characteristic (ROC) area under the curve=0.89) for separating the aPL+ and SSA/SSB+ SLE subgroups was integrin beta-1 (ITGB1), with higher levels present in the SSA/SSB+ subgroup. Proteins with the lowest p values comparing the two SLE subgroups were ITGB1, SLC13A3, and CERS5. These three proteins, rheumatoid factor, and immunoglobulin G (IgG) were all increased in the SSA/SSB+ subgroup. This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma. In the aPL+ subgroup, complement activation was more pronounced together with several biomarkers associated with systemic inflammation (fibrinogen, -1 antitrypsin, neutrophils, and triglycerides).ConclusionsOur observations indicate underlying pathogenic differences between the SSA/SSB+ and the aPL+ SLE subgroups, suggesting that the SSA/SSB+ subgroup may benefit from IFN-blocking therapies while the aPL+ subgroup is more likely to have an effect from drugs targeting the complement system. Stratifying SLE patients based on an autoantibody profile could be a way forward to understand underlying pathophysiology and to improve selection of patients for clinical trials of targeted treatments.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Systemic lupus erythematosus
- Antiphospholipid syndrome
- Sjogren's syndrome
- Personalized medicine
- Affinity-based proteomics
- Subgroups
- Affinity-based proteomics
- Antiphospholipid syndrome
- Personalized medicine
- Sjögren's syndrome
- Subgroups
- Systemic lupus erythematosus
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Idborg, Helena
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Zandian, Arash
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Sandberg, Ann-So ...
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Nilsson, Bo
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Elvin, Kerstin
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Truedsson, Lenna ...
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visa fler...
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Sohrabian, Azita
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Rönnelid, Johan
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Mo, John
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Grosso, Giorgia
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Kvarnström, Mari ...
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Gunnarsson, Iva
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Lehtio, Janne
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Nilsson, Peter
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Svenungsson, Eli ...
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Jakobsson, Per-J ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
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Arthritis Resear ...
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Kungliga Tekniska Högskolan
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Uppsala universitet
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Lunds universitet
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Karolinska Institutet