liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Segelmark, Mårten
Alternative names
Publications (10 of 115) Show all publications
Ingelsson, B., Söderberg, D., Strid, T., Söderberg, A., Bergh, A.-C., Loitto, V.-M., . . . Rosén, A. (2018). Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C.. Proceedings of the National Academy of Sciences of the United States of America, 115(3), E478-E487
Open this publication in new window or tab >>Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C.
Show others...
2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 3, p. E478-E487Article in journal (Refereed) Published
Abstract [en]

Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.

Place, publisher, year, edition, pages
Washington, DC, United States: National Academy of Sciences, 2018
Keyword
CpG-C, DAMP, immune DNA sensing, lymphocyte signaling, mitochondrial DNA release
National Category
Basic Medicine Immunology in the medical area
Research subject
Economic Information Systems
Identifiers
urn:nbn:se:liu:diva-144187 (URN)10.1073/pnas.1711950115 (DOI)000423091400018 ()29295921 (PubMedID)
Funder
Swedish Cancer Society
Note

Funding agencies: Linkoping Medical Society; Linkoping University; ALF grants; Region Ostergotland, Sweden; Linkoping University Cancer; Ingrid Asp Foundation; Swedish Cancer Society

Available from: 2018-01-09 Created: 2018-01-09 Last updated: 2018-02-12Bibliographically 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.
Show others...
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
Keyword
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
Söderberg, D. & Segelmark, M. (2016). Neutrophil Extracellular Traps in ANCA-Associated Vasculitis. Frontiers in Immunology, 7(UNSP 256)
Open this publication in new window or tab >>Neutrophil Extracellular Traps in ANCA-Associated Vasculitis
2016 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, no UNSP 256Article, review/survey (Refereed) Published
Abstract [en]

A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in the pathogenesis of AAV. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally, it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. AAV patients also possess elevated levels of NETs in the circulation. ANCAs are capable of inducing NETosis in neutrophils, and their potential to do so has been shown to be affinity dependent and to correlate with disease activity. Neutrophils from AAV patients are also more prone to release NETs spontaneously than neutrophils from healthy blood donors. NETs contain proinflammatory proteins and are thought to contribute to vessel inflammation directly by damaging endothelial cells and by activating the complement system and indirectly by acting as a link between the innate and adaptive immune system through the generation of PR3-and MPO-ANCA. Injection of NET-loaded myeloid dendritic cells into mice results in circulating PR3-and MPO-ANCA and the development of AAV-like disease. NETs have also been shown to be essential in a rodent model of drug-induced vasculitis. NETs induced by propylthiouracil could not be degraded by DNaseI, implying that disordered NETs might be important for the generation of ANCAs. NET degradation was also highlighted in another study showing that AAV patients have reduced DNaseI activity resulting in less NET degradation. With this in mind, it might be that prolonged exposure to proteins in the NETs due to the overproduction of NETs and/or reduced clearance of NETs is important in AAV. However, not all ANCAs are pathogenic and some might possibly also aid in the clearance of NETs. A dual role for ANCAs in relation to circulating NET levels has been proposed because a negative correlation was observed between PR3-ANCA and NET remnants in patients in remission.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2016
Keyword
neutrophil extracellular traps; ANCA-associated vasculitis; ANCA; NET; small-vessel vasculitis; NET remnants
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-130425 (URN)10.3389/fimmu.2016.00256 (DOI)000379119800001 ()27446086 (PubMedID)
Note

Funding Agencies|Ingrid Asps Foundation; Swedish Society of Nephrology; Swedish Renal Foundation

Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2018-01-10
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
Show others...
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
Keyword
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
van de Luijtgaarden, M. W. M., Jager, K. J., Segelmark, M., Pascual, J., Collart, F., Hemke, A. C., . . . Noordzij, M. (2016). Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period. Nephrology, Dialysis and Transplantation, 31(1), 120-128
Open this publication in new window or tab >>Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period
Show others...
2016 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 1, p. 120-128Article in journal (Refereed) Published
Abstract [en]

Background. Although previous studies suggest similar patient survival for peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide. We aimed to study trends in the choice of first dialysis modality and relate these to variation in patient and technique survival and kidney transplant rates in Europe over the last 20 years. Methods. We used data from 196 076 patients within the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started renal replacement therapy (RRT) between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91 after commencing RRT were quantified with Joinpoint regression. Crude and adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival were calculated using Cox regression. Analyses were repeated using propensity score matching to control for confounding by indication. Results. PD prevalence dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD and HD decreased from 2000 and 2009, respectively, while the incidence of kidney transplantation increased from 1993 onwards. Similar 5-year patient survival for PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003-07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared with 1993-97. Conclusions. Although initiating RRT on PD was associated with favourable patient survival when compared with starting on HD treatment, PD was often not selected as initial dialysis modality. Over time, we observed a significant decline in PD use and a stabilization inHD use. These observations were explained by the lower incidence rate of PD and HD and the increase in pre-emptive transplantation.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2016
Keyword
end-stage renal disease; haemodialysis; peritoneal dialysis; survival analysis; trends over time
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126862 (URN)10.1093/ndt/gfv295 (DOI)000371234600018 ()26311215 (PubMedID)
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30
Lindberg, U., Carlsson, M., Hellmark, T. & Segelmark, M. (2015). BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients. JOURNAL OF IMMUNOLOGY RESEARCH, 2015, 8, Article ID 947934.
Open this publication in new window or tab >>BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients
2015 (English)In: JOURNAL OF IMMUNOLOGY RESEARCH, ISSN 2314-8861, Vol. 2015, p. 8-, article id 947934Article in journal (Refereed) Published
Abstract [en]

Patients with cystic fibrosis (CF) colonized with Pseudomonas aeruginosa (P. aeruginosa) have worse prognosis compared with patients who are not. BPI-ANCA is an anti-neutrophil cytoplasmic antibody against BPI (bactericidal/permeability increasing protein) correlating with P. aeruginosa colonization and adverse long time prognosis. Whether it provides additional information as compared to standard anti-P. aeruginosa serology tests is not known. 117 nontransplanted CF patients at the CF centre in Lund, Sweden, were followed prospectively for ten years. Bacterial colonisation was classified according to the Leeds criteria. IgA BPI-ANCA was compared with assays for antibodies against alkaline protease (AP), Elastase (ELA), and Exotoxin A (ExoA). Lung function and patient outcome, alive, lung transplanted, or dead, were registered. BPI-ANCA showed the highest correlation with lung function impairment with an r-value of 0.44. Forty-eight of the 117 patients were chronically colonized with P. aeruginosa. Twenty of these patients experienced an adverse outcome. Receiver operator curve (ROC) analysis revealed that this could be predicted by BPI-ANCA (AUC = 0.77), (p = 0.002) to a better degree compared with serology tests. BPI-ANCA correlates better with lung function impairment and long time prognosis than anti-P. aeruginosa serology and has similar ability to identify patients with chronic P. aeruginosa.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2015
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-120890 (URN)10.1155/2015/947934 (DOI)000359240700001 ()26273683 (PubMedID)
Note

Funding Agencies|Bengt Andreasson Foundation; Heart and Lung Association in Sweden

Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2015-09-17
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.
Show others...
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
Venetsanos, D., Alfredsson, J., Segelmark, M., Swahn, E. & Lawesson, S. (2015). Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR. BMJ Open, 5(9), 1-8, Article ID e007835.
Open this publication in new window or tab >>Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
Show others...
2015 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, p. 1-8, article id e007835Article in journal (Refereed) Published
Abstract [en]

Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2015
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-122794 (URN)10.1136/bmjopen-2015-007835 (DOI)000363484000021 ()26399570 (PubMedID)
Available from: 2015-11-23 Created: 2015-11-23 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.
Show others...
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
Show others...
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
Keyword
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: 2017-12-01
Organisations

Search in DiVA

Show all publications