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Li, H., Ragna Reksten, T., Ice, J. A., Kelly, J. A., Adrianto, I., Rasmussen, A., . . . Sivils, K. L. (2017). Identification of a Sjögrens syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genetics, 13(6), Article ID e1006820.
Open this publication in new window or tab >>Identification of a Sjögrens syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
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2017 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 6, article id e1006820Article in journal (Refereed) Published
Abstract [en]

Sjogrens syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2-5-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3 end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-139633 (URN)10.1371/journal.pgen.1006820 (DOI)000404512600013 ()28640813 (PubMedID)2-s2.0-85021781632 (Scopus ID)
Note

Funding Agencies|NIH [P50AR0608040, 1R01AR065953, 5R01DE015223, 5RC2AR058959, 5P01AR049084, 5P30AR053483, 5U19AI082714, U19AI056363, 1R01DE018209, 5R01DE018209, 8P20GM103456, 1P30GM110766, 1R03AR065786, 5R37AI024717, 5P01AI083194, 7S10RR027190-02, 1U01AI101934, U54GM104938, S10RR026735, 5P30GM103510]; National Institute of Dental and Craniofacial Research; US Department of Veterans Affairs IM MA 9; USA Department of Defense [PR094002]; American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award; Oklahoma Medical Research Foundation; Sjogrens Syndrome Foundation; Phileona Foundation; French ministry of health: PHRC [2006-AOM06133]; French ministry of research [ANR-2010-BLAN-1133]

Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2018-01-13Bibliographically approved
Sandin, C., Eriksson, P., Segelmark, M., Skogh, T. & Kastbom, A. (2016). IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.. Clinical and Experimental Immunology, 184(2), 208-215
Open this publication in new window or tab >>IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.
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2016 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 184, no 2, p. 208-215Article in journal (Refereed) Published
Abstract [en]

Circulating IgA class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were similarly represented among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA positive patients were significantly higher as compared to inactive disease. Eight patients were prospectively sampled during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA more often turned negative after remission induction as compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are more closely related to disease activity in AAV as compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B-cell activation during active disease. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
ANCA-associated vasculitis; IgA PR3-ANCA; Mucosal immunity; disease activity
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-125664 (URN)10.1111/cei.12769 (DOI)000374689500007 ()26762653 (PubMedID)
Note

Funding agencies:  Swedish Society of Medicine; Reinhold Sund foundation for Rheumatology Research; Swedish Association against Rheumatism; Ostergotland County Council

Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2017-11-30
Vorkapic, E., Dugic, E., Vikingsson, S., Roy, J., Mäyränpää, M. I., Eriksson, P. & Wågsäter, D. (2016). Imatinib treatment attenuates growth and inflammation of angiotensin II induced abdominal aortic aneurysm. Atherosclerosis, 249, 101-109
Open this publication in new window or tab >>Imatinib treatment attenuates growth and inflammation of angiotensin II induced abdominal aortic aneurysm
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2016 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 249, p. 101-109Article in journal (Refereed) Published
Abstract [en]

AbstractBackground Abdominal aortic aneurysm (AAA) is characterized by vascular remodeling with increased infiltration of inflammatory cells and apoptosis/modulation of vascular smooth muscle cells (SMCs). Imatinib is a selective inhibitor of several tyrosine kinases, including PDGF receptors, Abl, and c-kit. The objective of this study was to characterize the potential protective role of imatinib on AAA development and the molecular mechanisms involved. Methods Male ApoE−/− mice were infused with angiotensin (Ang) II (1000 ng/kg/min) for 4 weeks to induce AAA or saline as controls. Daily treatment with 10 mg/kg imatinib, or tap water as control, was provided via gavage for 4 weeks. Results Treatment with imatinib was found to decrease the aortic diameter and vessel wall thickness, mediated by multiple effects. Imatinib treatment in AngII infused mice resulted in a reduced cellular infiltration of CD3ε positive T lymphocytes by 86% and reduced gene expression of mast cell chymase by 50% compared with AngII infused mice lacking imatinib. Gene expression analysis of SMC marker SM22α demonstrated an increase by 48% together with a more intact medial layer after treatment with imatinib as evaluated with SM22α immunostaining. Conclusion Present findings highlight the importance of tyrosine kinase pathways in the development of AAA. Our results show, that imatinib treatment inhibits essential mast cell, T lymphocyte and SMC mediated processes in experimental AAA. Thus, our results support the idea that tyrosine kinase inhibitors may be useful in the treatment of pathological vascular inflammation and remodeling in conditions like AAA.

Keywords
Abdominal aortic aneurysm, Vascular inflammation, Imatinib, Angiotensin II
National Category
Cell and Molecular Biology Physiology
Identifiers
urn:nbn:se:liu:diva-127501 (URN)10.1016/j.atherosclerosis.2016.04.006 (DOI)000376505800016 ()27085160 (PubMedID)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2018-01-10Bibliographically approved
Geetha, D., Hruskova, Z., Segelmark, M., Hogan, J., Morgan, M. D., Cavero, T., . . . Jayne, D. R. (2016). Rituximab for treatment of severe renal disease in ANCA associated vasculitis. JN. Journal of Nephrology (Milano. 1992), 29(2), 195-201
Open this publication in new window or tab >>Rituximab for treatment of severe renal disease in ANCA associated vasculitis
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2016 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed) Published
Abstract [en]

Background

Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

Methods

We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

Results

A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

Conclusions

This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

Place, publisher, year, edition, pages
Springer, 2016
Keywords
Rituximab; Renal disease; ANCA vasculitis
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:liu:diva-124009 (URN)10.1007/s40620-015-0208-y (DOI)000372244700008 ()25986390 (PubMedID)
Note

Funding agencies:  National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) [UL1 TR 001079]; NIH Roadmap for Medical Research

Available from: 2016-01-18 Created: 2016-01-18 Last updated: 2017-11-30Bibliographically approved
Liu, K., Kurien, B. T., Zimmerman, S. L., Kaufman, K. M., Taft, D. H., Kottyan, L. C., . . . Hal Scofield, R. (2016). X Chromosome Dose and Sex Bias in Autoimmune Diseases. Arthritis & Rheumatology, 68(5), 1290-1300
Open this publication in new window or tab >>X Chromosome Dose and Sex Bias in Autoimmune Diseases
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2016 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 68, no 5, p. 1290-1300Article in journal (Refereed) Published
Abstract [en]

Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128940 (URN)10.1002/art.39560 (DOI)000375551600030 ()26713507 (PubMedID)
Note

Funding Agencies|NIH [AR-062755, AI-024717, AI-031584, AI-062629, AI-063274, AI-082714, AI-083194, AI-101934]; NIH (National Institute of Dental and Craniofacial Research Intramural Research Program); University of Oklahoma Health Sciences Center (Clinical and Translational Science OCTSI Summer Scholar Program); US Department of Veterans Affairs [IMMA9]; US Department of Defense [PR094002]; Alliance for Lupus Research; Kirkland Scholar Program; Strategic Research Program at Helse Bergen; Western Norway Regional Health Authority; Broegelmann Foundation; French Ministry of Health (EvASSESS Programme Hospitalier de Recherche Clinique); Swedish Rheumatism Foundation; Arthritis Australia; Research to Prevent Blindness; Medical Research Council, UK [G0800629]; DFG [KFO 250 WI 1031/6-1]; Canadian Institutes of Health Research [MOP89955, MOP74621]; Ontario Research Fund [RE05-075]; Canada Research Chair Program; Instituto de Salud Carlos III (ISCIII through FEDER) [02558]; Allergan; Lilly; UCB; The NIH [AR-042460, AR-048204, AR-048940, AR-049084, AR-052125, AR-053483, AR-053734, AR-056360, AR-058959, AR-062277, AR-043814, AR-065626, DE-015223, DE-018209, RR-020143, GM-103510, GM-104938, HG-008667, TR-001475, HG-006828]

Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2017-11-30
Skoglund, C., Carlsen, A. L., Weiner, M., Kurz, T., Hellmark, T., Eriksson, P., . . . Segelmark, M. (2015). Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody associated vasculitis from healthy controls.. Clinical and Experimental Rheumatology, 33(2 Suppl 89), S64-S71
Open this publication in new window or tab >>Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody associated vasculitis from healthy controls.
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2015 (English)In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 33, no 2 Suppl 89, p. S64-S71Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV.

METHODS: Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data.

RESULTS: Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels.

CONCLUSIONS: In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:liu:diva-119924 (URN)000356402900011 ()26016752 (PubMedID)
Available from: 2015-06-30 Created: 2015-06-30 Last updated: 2017-12-04
Andersson, M., Jagervall, K., Eriksson, P., Persson, A., Granerus, G., Wang, C. & Smedby, Ö. (2015). How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance. BMC Medical Imaging, 15(42)
Open this publication in new window or tab >>How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance
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2015 (English)In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 15, no 42Article in journal (Refereed) Published
Abstract [en]

Background: Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. Methods: Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. Results: A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82-0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists visual assessments on CTA and MRA were 0.90 (0.82-0.98) and 0.91 (0.83-0.99) respectively. None of the differences were statistically significant. Conclusions: No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with fuzzy connectedness segmentation. Further studies are required to definitely identify the optimal measurement approach.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
Renal artery stenosis; Computed tomography angiography; Magnetic resonance angiography; Renography; Fuzzy connectedness segmentation; Vessel diameter; Cross-sectional area
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122418 (URN)10.1186/s12880-015-0086-8 (DOI)000362535400001 ()26459634 (PubMedID)
Note

Funding Agencies|Research Council of South-Eastern Sweden (FORSS); Swedish Research Council (VR)

Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2017-12-01
Mohammad, A. J., Weiner, M., Sjöwall, C., Johansson, M. E., Bengtsson, A. A., Ståhl-Hallengren, C., . . . Segelmark, M. (2015). Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden.. Nephrology, Dialysis and Transplantation, 30, i23-i30
Open this publication in new window or tab >>Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden.
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2015 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, p. i23-i30Article in journal (Refereed) Published
Abstract [en]

Objectives :The objectives of this study were to compare incidence rates, renal and patient survival between lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody-associated nephritis (AAN) during a 12-year period in two geographically defined populations in Sweden.

METHODS: In the health care districts surrounding the Skåne University Hospital in Lund [mean population ≥18 years (1997-2008), 188 400] and the University Hospital in Linköping [mean population ≥18 years (1997-2008), 328 900] all patients with biopsy-proven LN and AAN during the period 1997-2008 were included in the study if they (i) were residing within the study areas at the time of onset of nephritis, (ii) had a clinical diagnosis of either SLE or ANCA-associated vasculitis (AAV) and (iii) experienced a first flare of biopsy-proven nephritis during the study period.

RESULTS: Eighty-two patients (Lund 44 + Linköping 38) with biopsy-proven AAN were identified and 27 patients with LN (Lund 13 + Linköping 14). The annual incidence rate per million inhabitants aged ≥18 years in both study areas was estimated to be 13.2 (95% CI 10.4-16.1) for AAN and 4.3 (95% CI 2.7-6.0) for LN, P < 0.001. The patients were followed until January 2013. During the follow-up time 38 patients died (AAN 36, LN 2; P = 0.001), and 20 patients went into end-stage renal disease (AAN 19 and LN 1), P = 0.020.

CONCLUSIONS: In Sweden, AAN was three times more common than LN, and the outcome was considerably worse. SLE is often diagnosed before the onset of nephritis leading to earlier treatment, while AAN is still often diagnosed at a later stage.

Place, publisher, year, edition, pages
Oxford University Press, 2015
National Category
Basic Medicine Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-113101 (URN)10.1093/ndt/gfu396 (DOI)000353500300005 ()25540097 (PubMedID)
Available from: 2015-01-09 Created: 2015-01-09 Last updated: 2018-01-11
Söderberg, D., Kurz, T., Motamedi, A., Hellmark, T., Eriksson, P. & Segelmark, M. (2015). Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission. Rheumatology, 54(11), 2085-2094
Open this publication in new window or tab >>Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission
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2015 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 11, p. 2085-2094Article in journal (Refereed) Published
Abstract [en]

Objectives. Neutrophil extracellular traps (NETs) have been visualized at the site of ANCA-associated vasculitis (AAV) lesions. Increased levels of NET remnants in the circulation have been reported in some AAV patients with active disease. The aim of the present study was to analyse NET remnants in a larger cohort of AAV patients with varying degrees of disease activity and to elucidate possible factors responsible for remnant variation. Methods. Levels of NET remnants in the circulation of healthy controls (HCs; n =31) and AAV patients (n =93) were determined with ELISA. NET remnants were then correlated with ANCA levels, spontaneous and induced cell death (NETosis/necrosis) in vitro, neutrophil count and corticosteroid therapy. Results. Patients with active disease showed higher levels of circulating NET remnants compared with patients in remission (P=0.026) and HCs (P=0.006). From patients sampled during both remission and active disease, we found increased levels during active disease (P=0.0010). In remission, ANCA-negative patients had higher levels of NET remnants than ANCA-positive patients and a negative correlation was observed between NET remnants and PR3-ANCA (rs = 0.287, P=0.048). NET remnants correlated with neutrophil count in HCs (rs =0.503, P=0.014) but not in patients during remission. Neutrophils from patients showed enhanced spontaneous cell death (P=0.043). Conclusion. We found increased levels of circulating NET remnants in patients with active AAV. Furthermore, AAV patients exhibited an increased propensity for spontaneous cell death. NET remnant levels seem to be positively related to disease activity and neutrophil count, but inversely related to ANCA at least during remission.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2015
Keywords
small vessel vasculitis; ANCA-associated vasculitis; neutrophil extracellular trap (NET); NET remnants; ANCA
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123334 (URN)10.1093/rheumatology/kev217 (DOI)000364760700023 ()26170375 (PubMedID)
Available from: 2015-12-14 Created: 2015-12-11 Last updated: 2018-07-18
Eriksson, P., Andersson, C., Cassel, P., Nyström, S. & Ernerudh, J. (2015). Letter: Increase in Th17-associated CCL20 and decrease in Th2-associated CCL22 plasma chemokines in active ANCA-associated vasculitis [Letter to the editor]. Scandinavian Journal of Rheumatology, 44(1), 80-83
Open this publication in new window or tab >>Letter: Increase in Th17-associated CCL20 and decrease in Th2-associated CCL22 plasma chemokines in active ANCA-associated vasculitis
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2015 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 1, p. 80-83Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Informa Healthcare, 2015
National Category
Clinical Medicine Immunology in the medical area Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114016 (URN)10.3109/03009742.2014.952332 (DOI)000347408000013 ()25352172 (PubMedID)
Available from: 2015-02-06 Created: 2015-02-05 Last updated: 2018-01-11
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ORCID iD: ORCID iD iconorcid.org/0000-0002.3555-7162

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