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Article: Factors Associated with Survival and Discontinuation of Anti-Malarial Agents in Systemic Lupus Erythematosus: Results from a Tertiary Swedish Referral Centre.

Walhelm, Tomas / Wirestam, Lina / Enman, Yvonne / Parodis, Ioannis / Sjöwall, Christopher

2024 Volume 13, Issue 5

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2024-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13051485
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Article: Serum serotonin levels are elevated in patients with increased risk of rheumatoid arthritis.

Wirestam, Lina / Martinsson, Klara / Kastbom, Alf

Frontiers in medicine

2023 Volume 9, Page(s) 1081814

Abstract: Background: Even though serotonin (5-HT) has been ascribed immunomodulatory features, very little is known about its role in chronic inflammatory diseases. Serotonin is implicated in inflammation and increased levels have been associated with ... ...

Abstract	Background: Even though serotonin (5-HT) has been ascribed immunomodulatory features, very little is known about its role in chronic inflammatory diseases. Serotonin is implicated in inflammation and increased levels have been associated with progression of bone erosions in RA. Objective: To investigate serum serotonin levels in patients with increased risk of rheumatoid arthritis (RA) and patients with recent-onset disease. Moreover, we aimed to determine the prognostic value of serotonin for arthritis development and the disease course. Methods: Two prospective observational patient cohorts were studied; anti-citrullinated protein antibody (ACPA) -positive patients with musculoskeletal pain without clinical arthritis ( Results: Compared to healthy controls (median 65 ng/ml), serotonin levels were significantly higher in both at-risk individuals (median 111 ng/ml, Conclusion: Serum serotonin levels are elevated both at, and prior to, onset of RA. However, increased serotonin is not prognostic for arthritis development or disease course.
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1081814
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Article ; Online: Serum levels of soluble urokinase plasminogen activator receptor in juvenile idiopathic arthritis: a single-center Swedish case-control study.

Lewander, Per / Wirestam, Lina / Dahle, Charlotte / Wetterö, Jonas / Sjöwall, Christopher

Pediatric rheumatology online journal

2023 Volume 21, Issue 1, Page(s) 49

Abstract: Objectives: Reliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order ... ...

Abstract	Objectives: Reliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order to individualize treatment and follow-up in JIA. The soluble urokinase plasminogen activator receptor (suPAR) has been reported as an easily measurable biomarker for prognosis and severity in several rheumatic diseases but it has never been studied in JIA. Methods: Sera from 51 well-characterized patients with JIA and 50 age- and sex-matched control subjects were collected and stored for later analysis of suPAR. Patients were carefully followed clinically over 3 years and analysis of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed as part of clinical routine. Signs of joint erosions were evaluated by radiography. Results: Overall, the levels of suPAR did not differ significantly between JIA patients and controls but those with polyarticular involvement showed higher suPAR (p = 0.013). In addition, elevated suPAR were associated with joint erosions (p = 0.026). Two RF/anti-CCP negative individuals with erosions showed high levels of suPAR. Conclusions: We present new data on the biomarker suPAR in JIA. Our results indicate that, apart from RF and anti-CCP, analysis of suPAR could be of additional value in assessing the risk of erosions. Analysis of suPAR early could potentially guide treatment decision-making in JIA, but our observations should be confirmed in prospective studies.
MeSH term(s)	Humans ; Arthritis, Juvenile ; Receptors, Urokinase Plasminogen Activator ; Sweden/epidemiology ; Case-Control Studies ; Prospective Studies ; Anti-Citrullinated Protein Antibodies ; Rheumatoid Factor ; Biomarkers ; Prognosis
Chemical Substances	Receptors, Urokinase Plasminogen Activator ; Anti-Citrullinated Protein Antibodies ; Rheumatoid Factor (9009-79-4) ; Biomarkers
Language	English
Publishing date	2023-05-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-023-00832-9
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Article: Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature.

Eriksson, Per / Mölne, Johan / Wirestam, Lina / Sjöwall, Christopher

Frontiers in medicine

2021 Volume 8, Page(s) 661101

Abstract: Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for ... ...

Abstract	Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.
Language	English
Publishing date	2021-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.661101
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Article ; Online: Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab

Per Eriksson / Johan Mölne / Lina Wirestam / Christopher Sjöwall

Frontiers in Medicine, Vol

Report of Two Cases and Review of the Literature

2021 Volume 8

Abstract	Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.
Keywords	amyloidosis—diagnosis ; ankylosing spondylitis ; interleukin-6 ; nephropathy ; proteinuria—nephrotic syndrome ; tocilizumab ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article: Plasma Osteopontin Reflects Tissue Damage in Acute Pancreatitis.

Wirestam, Lina / Nyberg, Pernilla Benjaminsson / Dzhendov, Todor / Gasslander, Thomas / Sandström, Per / Sjöwall, Christopher / Björnsson, Bergthor

Biomedicines

2023 Volume 11, Issue 6

Abstract: Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, ... ...

Abstract	Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, but the significance of OPN in AP has not yet been established. We aimed to evaluate plasma levels of OPN in relation to the severity of AP. In 39 individuals with confirmed AP, plasma was collected on the day of admission and consecutively for three days thereafter. Sex- and age-matched healthy blood donors (
Language	English
Publishing date	2023-06-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11061627
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Article ; Online: Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy.

Wirestam, Lina / Pihl, Sofia / Saleh, Muna / Wetterö, Jonas / Sjöwall, Christopher

Frontiers in immunology

2021 Volume 12, Page(s) 722118

Abstract: Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver- ... ...

Abstract	Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver-derived. In addition, increased levels of PTX3 have been linked to preeclampsia. Reference intervals are usually based on healthy blood donors. Several physiological and immunological alterations occur during normal pregnancy with subsequent potential effects on blood analytes. Hence, this study aims to determine pregnancy-specific reference intervals for CRP and PTX3. Longitudinal clinical data and blood plasma samples from the 1
MeSH term(s)	Adult ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Pregnancy ; Reference Values ; Serum Albumin, Human ; Serum Amyloid P-Component/metabolism ; Young Adult
Chemical Substances	Biomarkers ; Serum Amyloid P-Component ; PTX3 protein (148591-49-5) ; C-Reactive Protein (9007-41-4) ; Serum Albumin, Human (ZIF514RVZR)
Language	English
Publishing date	2021-08-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.722118
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Article ; Online: Limited Association between Antibodies to Oxidized Low-Density Lipoprotein and Vascular Affection in Patients with Established Systemic Lupus Erythematosus.

Wirestam, Lina / Jönsson, Frida / Enocsson, Helena / Svensson, Christina / Weiner, Maria / Wetterö, Jonas / Zachrisson, Helene / Eriksson, Per / Sjöwall, Christopher

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Patients with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease. We aimed to evaluate whether antibodies to oxidized low-density lipoprotein (anti-oxLDL) were associated with subclinical atherosclerosis in patients ... ...

Abstract	Patients with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease. We aimed to evaluate whether antibodies to oxidized low-density lipoprotein (anti-oxLDL) were associated with subclinical atherosclerosis in patients with different SLE phenotypes (lupus nephritis, antiphospholipid syndrome, and skin and joint involvement). Anti-oxLDL was measured by enzyme-linked immunosorbent assay in 60 patients with SLE, 60 healthy controls (HCs) and 30 subjects with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Intima-media thickness (IMT) assessment of vessel walls and plaque occurrence were recorded using high-frequency ultrasound. In the SLE cohort, anti-oxLDL was again assessed in 57 of the 60 individuals approximately 3 years later. The levels of anti-oxLDL in the SLE group (median 5829 U/mL) were not significantly different from those in the HCs group (median 4568 U/mL), while patients with AAV showed significantly higher levels (median 7817 U/mL). The levels did not differ between the SLE subgroups. A significant correlation was found with IMT in the common femoral artery in the SLE cohort, but no association with plaque occurrence was observed. The levels of anti-oxLDL antibodies in the SLE group were significantly higher at inclusion compared to 3 years later (median 5707 versus 1503 U/mL,
MeSH term(s)	Humans ; Carotid Intima-Media Thickness ; Lupus Erythematosus, Systemic/complications ; Antibodies ; Atherosclerosis/complications ; Plaque, Atherosclerotic/etiology ; Lipoproteins, LDL ; Risk Factors
Chemical Substances	Antibodies ; Lipoproteins, LDL
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108987
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Article ; Online: Extracellular vesicles opsonized by monomeric C-reactive protein (CRP) are accessible as autoantigens in patients with systemic lupus erythematosus and associate with autoantibodies against CRP.

Karlsson, Jesper / Wetterö, Jonas / Potempa, Lawrence A / Fernandez-Botran, Rafael / O'Neill, Yasmine / Wirestam, Lina / Mobarrez, Fariborz / Sjöwall, Christopher

Journal of autoimmunity

2023 Volume 139, Page(s) 103073

Abstract: The pentraxin C-reactive protein (CRP) is a pentameric protein now known to be able to undergo dissociation into a monomeric, modified isoform, referred to as mCRP. In carefully assessing the bioactivities of each isoform, mCRP has strong pro- ... ...

Abstract	The pentraxin C-reactive protein (CRP) is a pentameric protein now known to be able to undergo dissociation into a monomeric, modified isoform, referred to as mCRP. In carefully assessing the bioactivities of each isoform, mCRP has strong pro-inflammatory activities while pCRP has mild anti-inflammatory activities. Systemic lupus erythematosus (SLE) is a disease characterized by a vast number of autoantibodies, including anti-CRP autoantibodies which have been associated with SLE disease activity and lupus nephritis. The origin of these autoantibodies is currently unknown. Extracellular vesicles (EVs) have been implicated in SLE pathogenesis as they can expose nuclear antigens on their outside surface, thereby being a potential adjuvant for the generation of autoantibodies. Herein, we studied exposure of both pCRP and mCRP on EVs in SLE plasma and the implications of each in disease activity, organ damage and clinical manifestations. We used flow cytometry to detect CRP isoforms on EV surfaces in 67 well-characterized SLE patients and 60 sex- and age-matched healthy controls. Autoantibodies against mCRP were measured using ELISA. We found an abundance of both pCRP and mCRP on SLE EVs compared to controls. Furthermore, mCRP
MeSH term(s)	Humans ; C-Reactive Protein/metabolism ; Lupus Nephritis/diagnosis ; Autoantibodies ; Autoantigens ; Lupus Erythematosus, Systemic ; Extracellular Vesicles/metabolism ; Protein Isoforms
Chemical Substances	C-Reactive Protein (9007-41-4) ; Autoantibodies ; Autoantigens ; Protein Isoforms
Language	English
Publishing date	2023-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2023.103073
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Article ; Online: Plasma Osteopontin Reflects Tissue Damage in Acute Pancreatitis

Lina Wirestam / Pernilla Benjaminsson Nyberg / Todor Dzhendov / Thomas Gasslander / Per Sandström / Christopher Sjöwall / Bergthor Björnsson

Biomedicines, Vol 11, Iss 1627, p

2023 Volume 1627

Abstract	Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, but the significance of OPN in AP has not yet been established. We aimed to evaluate plasma levels of OPN in relation to the severity of AP. In 39 individuals with confirmed AP, plasma was collected on the day of admission and consecutively for three days thereafter. Sex- and age-matched healthy blood donors ( n = 39) served as controls. Plasma OPN was measured by a commercial enzyme-linked immunosorbent assay. At admission, patients with AP displayed higher OPN, 156.4 ng/mL (IQR 111.8–196.2) compared to controls, 37.4 ng/mL (IQR 11.7–65.7) ( p < 0.0001). However, OPN levels on admission could not discriminate between mild and moderate-to-severe disease (132.6 ng/mL vs. 163.4 ng/mL). Nevertheless, the changes in OPN within 24 h of admission and Day 2/3 were higher among patients with moderate/severe AP (33.7%) compared to mild AP (−8.1%) ( p = 0.01). This indicates that OPN is a relevant biomarker reflecting tissue injury in AP. The increase in OPN over time suggests that serial OPN measurements could contribute to the early detection of at-risk patients. Prospective studies assessing OPN in relation to outcome in AP are warranted.
Keywords	osteopontin ; acute pancreatitis ; organ damage ; biomarker ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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