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Sjöwall, Christoffer
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Publications (10 of 57) Show all publications
Wirestam, L., Enocsson, H., Skogh, T., Padyukov, L., Jonsen, A., Urowitz, M. B., . . . Sjöwall, C. (2019). Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort. Journal of Rheumatology, 46(5), 492-500
Open this publication in new window or tab >>Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort
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2019 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 46, no 5, p. 492-500Article in journal (Refereed) Published
Abstract [en]

Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age-and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p amp;lt; 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI amp;gt;= 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p amp;lt; 0.0001), and patients with high disease activity (SLEDAI-2K amp;gt;= 5) had raised serum OPN (p amp;lt; 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p amp;lt; 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Place, publisher, year, edition, pages
J RHEUMATOL PUBL CO, 2019
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; BIOMARKERS; OSTEOPONTIN; DISEASE ACTIVITY; ORGAN DAMAGE; PROGNOSIS
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-156906 (URN)10.3899/jrheum.180713 (DOI)000466402600010 ()30647177 (PubMedID)
Note

Funding Agencies|Swedish Rheumatism Association; County Council of Ostergotland; Swedish Society of Medicine; King Gustaf V and Queen Victorias Freemasons foundation; King Gustaf Vs 80-year anniversary foundation; Hanyang University [201600000001387]; Lupus UK; NIHR/Wellcome Trust Clinical Research Facility; US National Institutes of Health (NIH) [AR43727]; Singer Family Fund for Lupus Research; Arthritis Research UK; NIHR Manchester Biomedical Research Centre; NIHR/Wellcome Trust Clinical Research Facility at Manchester University National Health Service (NHS) Foundation Trust; Danish Rheumatism Association [A1028]; NIH [RR00046]

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-06-18
Parodis, I., Gomez, A., Frodlund, M., Jönsen, A., Zickert, A., Sjöwall, C., . . . Gunnarsson, I. (2018). Smoking reduces the efficacy of belimumab in mucocutaneous lupus.. Expert Opinion on Biological Therapy, 18(8), 911-920
Open this publication in new window or tab >>Smoking reduces the efficacy of belimumab in mucocutaneous lupus.
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2018 (English)In: Expert Opinion on Biological Therapy, ISSN 1471-2598, E-ISSN 1744-7682, Vol. 18, no 8, p. 911-920Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Recently, we demonstrated a negative impact of smoking on belimumab efficacy in patients with systemic lupus erythematosus (SLE). Here, we particularly investigated clinical effects of belimumab and a potential impact of smoking in mucocutaneous and articular SLE.

METHODS: We surveyed 62 SLE patients treated between 2011 and 2017. Evaluation included the mucocutaneous descriptors of SLEDAI-2K (rash, alopecia, mucosal ulcers; mcSLEDAI-2K), CLASI, the arthritis SLEDAI-2K descriptor (arSLEDAI-2K) and the 28-joint count.

RESULTS: mcSLEDAI-2K and CLASI activity decreased from baseline to month 6 and 12 (P<0.001 for all). No worsening in CLASI damage was observed. Current or previous smokers displayed a higher probability of unchanged/worsened mcSLEDAI-2K compared to never smokers (OR: 6.4; 95% CI: 1.5-27.4; P=0.012), also after adjustment for antimalarial agents. arSLEDAI-2K scores had decreased at month 6 (P<0.001) and 12 (P<0.001). Likewise, tender and swollen 28-joint counts had improved at month 6 (P=0.010 and P<0.001, respectively) and 12 (P=0.001 for both). We observed no impact of smoking on belimumab efficacy in articular SLE.

CONCLUSION: We observed a negative impact of smoking on the efficacy of belimumab in mucocutaneous SLE. In contrast, no impact of smoking on belimumab efficacy was seen in patients with articular manifestations.

Place, publisher, year, edition, pages
Informa Healthcare, 2018
Keywords
belimumab, biological agents, drug efficacy, rheumatology, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-149494 (URN)10.1080/14712598.2018.1494719 (DOI)000445196000008 ()29958508 (PubMedID)
Available from: 2018-07-03 Created: 2018-07-03 Last updated: 2019-04-10
Arkema, E. V., Jönsen, A., Rönnblom, L., Svenungsson, E., Sjöwall, C. & Simard, J. F. (2016). Case definitions in Swedish register data to identify systemic lupus erythematosus. BMJ Open, 6(1)
Open this publication in new window or tab >>Case definitions in Swedish register data to identify systemic lupus erythematosus
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2016 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.

METHODS: The reference standard consisted of clinically confirmed SLE cases pooled from four major clinical centres in Sweden (n=929), and a sample of non-SLE comparators randomly selected from the National Population Register (n=24 267). Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the reference standard. We first used previously published SLE definitions to create algorithms for SLE. We also used modern data mining techniques (penalised least absolute shrinkage and selection operator logistic regression, elastic net regression and classification trees) to objectively create data-driven case definitions. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the case definitions identified.

RESULTS: Defining SLE by using only hospitalisation data resulted in the lowest sensitivity (0.79). When SLE codes from the outpatient register were included, sensitivity and PPV increased (PPV between 0.97 and 0.98, sensitivity between 0.97 and 0.99). Addition of medication information did not greatly improve the algorithm's performance. The application of data mining methods did not yield different case definitions.

CONCLUSIONS: The use of SLE International Classification of Diseases (ICD) codes in outpatient clinics increased the accuracy for identifying individuals with SLE using Swedish registry data. This study implies that it is possible to use ICD codes from national registers to create a cohort of individuals with SLE.

Place, publisher, year, edition, pages
B M J Group, 2016
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-124005 (URN)10.1136/bmjopen-2015-007769 (DOI)000369993900007 ()26729375 (PubMedID)
Note

Funding agencies:  Strategic Research Programme in Epidemiology at Karolinska Institute; Stockholm County Council; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Rheumatism Foundation; King Gustaf V 80-year Foundation

Available from: 2016-01-18 Created: 2016-01-18 Last updated: 2017-11-30Bibliographically approved
Crisci, E., Ellegård, R., Nyström, S., Rondahl, E., Serrander, L., Bergström, T., . . . Larsson, M. (2016). Complement opsonization promotes HSV-2 infection of human dendritic cells. Journal of Virology, 90(10), 4939-4950
Open this publication in new window or tab >>Complement opsonization promotes HSV-2 infection of human dendritic cells
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2016 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed) Published
Abstract [en]

Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

Place, publisher, year, edition, pages
American society of microbiology, 2016
Keywords
HSV2 infection, dendritic cells, complement, antibodies
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-126480 (URN)10.1128/JVI.00224-16 (DOI)000375126100009 ()26937039 (PubMedID)
Note

Funding agencies: Swedish Research Council [AI52731]; Swedish Physicians Against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; Swedish Society of Medicine; Swedis

Available from: 2016-03-29 Created: 2016-03-29 Last updated: 2018-03-23
Jönsen, A., Hjalte, F., Willim, M., Carlsson, K. S., Sjöwall, C., Svenungsson, E., . . . Nived, O. (2016). Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts.. Seminars in Arthritis & Rheumatism, 45(6), 684-690
Open this publication in new window or tab >>Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts.
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2016 (English)In: Seminars in Arthritis & Rheumatism, ISSN 0049-0172, E-ISSN 1532-866X, Vol. 45, no 6, p. 684-690Article, review/survey (Refereed) Published
Abstract [en]

OBJECTIVES: The main objectives of this study were to calculate total costs of illness and cost-driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden.

METHODS: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency.

RESULTS: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941€), of which direct cost was 63,672kr ($10,188 = 7004€) and the indirect cost was 144,883 SEK ($23,181 = 15,937€), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs.

CONCLUSION: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (=129.5 million €). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs.

Place, publisher, year, edition, pages
Elsevier, 2016
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:liu:diva-124004 (URN)10.1016/j.semarthrit.2015.11.013 (DOI)000378668100007 ()26743074 (PubMedID)
Available from: 2016-01-18 Created: 2016-01-18 Last updated: 2017-11-30
Bentow, C., Lakos, G., Martis, P., Wahl, E., Garcia, M., Vinas, O., . . . Mahler, M. (2016). International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies. Lupus, 25(8), 864-872
Open this publication in new window or tab >>International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies
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2016 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 25, no 8, p. 864-872Article in journal (Refereed) Published
Abstract [en]

Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2016
Keywords
anti-dsDNA antibodies; autoantibodies; autoimmune disease; comparative study; diagnostic test; immunoassay; lupus; multicenter study; systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-130421 (URN)10.1177/0961203316640917 (DOI)000379238100010 ()27252263 (PubMedID)
Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2017-11-28
Nikiphorou, E., Sjöwall, C., Hannonen, P., Rannio, T. & Sokka, T. (2016). Long-term outcomes of destructive seronegative (rheumatoid) arthritis - description of four clinical cases. BMC Musculoskeletal Disorders, 17, Article ID 246.
Open this publication in new window or tab >>Long-term outcomes of destructive seronegative (rheumatoid) arthritis - description of four clinical cases
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2016 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, article id 246Article in journal (Refereed) Published
Abstract [en]

Background: Seronegative rheumatoid arthritis is associated with a milder course of progression compared to seropositive disease. However, long-term follow-up data of the clinical course of seronegative rheumatoid arthritis are sparse. Here we describe four cases with a rare disease entity of aggressive destructive seronegative (rheumatoid) arthritis with 20-35 years of follow-up. Case presentation: The four cases are women with an initial presentation of seronegative rheumatoid arthritis in 1980-1996 and have received disease-modifying anti-rheumatic drugs since the diagnosis. In all cases, the condition has been refractory to treatments and evolved into a severe disease with destructions of the wrists, sub-talar and ankle joints, as well as large joints but not small joints of fingers and toes. All cases are negative with regard to rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antibodies against carbamylated proteins. Conclusions: This report adds to the existing literature, making the reader aware of this sub-type of inflammatory arthritis which despite being seronegative, can have devastating disease consequences. The report highlights the need for further research into this field in order to better understand this disease sub-type, the pathogenesis, disease course and outcomes.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2016
Keywords
Rheumatoid arthritis; Seronegative; Erosions; Outcomes
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-129665 (URN)10.1186/s12891-016-1067-y (DOI)000377245800001 ()27256084 (PubMedID)
Note

Funding Agencies|Swedish Society for Medical Research; EULAR Scientific Training bursary

Available from: 2016-06-27 Created: 2016-06-23 Last updated: 2017-11-28
Arkema, E. V., Palmsten, K., Sjöwall, C., Svenungsson, E., Salmon, J. E. & Simard, J. F. (2016). What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population-Based Study of Maternal and Fetal Outcomes in SLE and Pre-SLE.. Arthritis care & research, 68(7)
Open this publication in new window or tab >>What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population-Based Study of Maternal and Fetal Outcomes in SLE and Pre-SLE.
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2016 (English)In: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 68, no 7Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To assess maternal and fetal outcomes associated with subclinical (pre-systemic lupus erythematosus [SLE] and SLE presenting up to 5 years postpartum) and prevalent maternal SLE during pregnancy compared with the general population.

METHODS: This prospective cohort study used population-based Swedish registers to identify 13,598 women with first singleton pregnancies registered in the Medical Birth Register (551 prevalent SLE, 65 pre-SLE within 0-2 years, 133 pre-SLE within 2-5 years, and 12,847 general population). SLE was defined as ≥2 SLE-coded discharge diagnoses in the patient register with ≥1 diagnosis from a specialist. Unadjusted risks of adverse pregnancy or birth outcomes were calculated by SLE status, and Cochran-Armitage tests evaluated trend across exposure groups.

RESULTS: Maternal outcomes such as preeclampsia, hypothyroidism, stroke, and infection were more common among women with SLE. Sixteen percent of prevalent-SLE pregnancies were diagnosed with preeclampsia compared with 5% of those from the general population. Among the pre-SLE women, preeclampsia was found in 26% of those with SLE within 2 years postpartum and 13% in those with SLE within 2-5 years postpartum. Similarly, infant outcomes, such as preterm birth, infection, and mortality, were worse among those born to mothers with prevalent SLE and pre-SLE during pregnancy. The test for trend was significant for most outcomes.

CONCLUSION: Our data demonstrate that adverse maternal and fetal outcomes are more common in SLE pregnancies. Furthermore, these unfavorable outcomes are observed in pregnancies occurring prior to the diagnosis of SLE. Thus, the underlying immunologic profile of SLE and alterations preceding clinical SLE may contribute to these pregnancy complications.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-129952 (URN)10.1002/acr.22791 (DOI)000379673700013 ()27338103 (PubMedID)
Note

Funding agencies: Strategic Research Program in Epidemiology at Karolinska Institute; County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz Foundation; King Gustaf V 80-Year

Available from: 2016-07-02 Created: 2016-07-02 Last updated: 2017-11-28
Sjöwall, C., Zapf, J., von Löhneysen, S., Magorivska, I., Biermann, M., Janko, C., . . . Muñoz, L. E. (2015). Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus. Lupus, 24(6), 569-581
Open this publication in new window or tab >>Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus
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2015 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 24, no 6, p. 569-581Article in journal (Refereed) Published
Abstract [en]

In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells.

Place, publisher, year, edition, pages
Sage Publications, 2015
Keywords
Aleura aurantia; IgG; Lens culinaris; SLEDAI; glycosylation; immune complex; lectin-ELISA; physicians global assessment
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-112700 (URN)10.1177/0961203314558861 (DOI)000353586100005 ()25389233 (PubMedID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2017-12-05
Wirestam, L., Schierbeck, H., Skogh, T., Gunnarsson, I., Ottosson, L., Erlandsson-Harris, H., . . . Sjöwall, C. (2015). Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus. Arthritis Research & Therapy, 17(338)
Open this publication in new window or tab >>Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus
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2015 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, no 338Article in journal (Refereed) Published
Abstract [en]

Introduction: The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodies can ameliorate murine polyarthritis and lupus-like disease. Interestingly, autoantibodies against HMGB1 have also been described in patients with systemic lupus erythematosus (SLE), but their clinical implications remain elusive. The main aims of this study were to detect serum anti-HMGB1 antibodies in patients with SLE and relate them to other types of antinuclear antibodies (ANA), and to disease activity. Methods: 188 Swedish SLE patients meeting the 1982 American College of Rheumatology classification criteria and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria participated in the study. Anti-HMGB1 antibody levels were analysed in patient and control (n = 112) sera by an in-house ELISA using recombinant histidine-tagged HMGB1. SLE sera were also analysed for ANA by immunofluorescence (IF) microscopy (IF-ANA) using fixed HEp-2 cells, and by a line-blot assay for antigen fine-specificities. To quantify antibodies to double-stranded DNA, a fluoroenzyme-immunoassay was employed. Results: At inclusion, 23 % of the SLE patients were anti-HMGB1 antibody positive compared to 5 % of the controls. Anti-HMGB1 antibodies occurred in 49 % of the IF-ANA positive SLE patients, and in 34 % of IF-ANA negative cases (p = 0.004). Levels of anti-HMGB1 antibodies correlated with anti-dsDNA antibody levels (r = 0.49; p less than 0.001). Significant, but less pronounced correlations were found regarding anti-HMGB1 and SLE disease activity index (SLEDAI-2K: r = 0.15; p = 0.04), classical complement function (r = -0.24; p = 0.002) and complement protein C4 (r = -0.23; p = 0.002). Average anti-HMGB1 antibody levels were significantly higher among patients with homogenous +/- other IF-ANA staining patterns (median 180 AU) compared to IF-ANA negative cases (median 83 AU) (p = 0.004). Rabbit anti-HMGB1 antibodies gave rise to cytoplasmic, but not nuclear, staining of HEp-2 cells. Conclusions: We confirm that anti-HMGB1 antibodies are common in SLE and correlate with disease activity variables. Although anti-HMGB1 antibodies measured by ELISA often coincide with nuclear IF-ANA staining, our results indicate that anti-HMGB1 antibodies do not give rise to nuclear staining of the predominantly used commercial HEp-2 cell slides.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
HMGB1; Autoantibodies; SLE; Antinuclear antibodies; Inflammation; Clinical phenotype; Complement proteins
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-123521 (URN)10.1186/s13075-015-0856-2 (DOI)000365252900001 ()26596890 (PubMedID)
Note

Funding Agencies|Swedish Society for Medical Research, Region Ostergotland; Swedish Research Council; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf Vs 80-year foundation

Available from: 2015-12-22 Created: 2015-12-21 Last updated: 2018-01-10
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