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- Manojlovic, M., et al.
(författare)
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Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)
- 2020
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Ingår i: Journal of Molecular Medicine. - : SPRINGER HEIDELBERG. - 0946-2716 .- 1432-1440. ; 98:9, s. 1279-1286
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Tidskriftsartikel (refereegranskat)abstract
- To investigate presence of circulating myeloperoxidase-positive microparticles (MPO(+)MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS >= 1). Concentrations of MPO(+)MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p< 0.001,p< 0.01,p< 0.001, respectively), while concentrations of PTX3(+)and HMGB1(+)MPO(+)MPs were significantly higher in active AAV compared to patients in remission. MPO(+)MPs expressing either PTX3 or HMGB1 were associated with BVAS (r= 0.5,p< 0.001;r= 0.3,p= 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p< 0.001), correlating strongly with BVAS (r= 0.7,p< 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO(+)MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO(+)MPs were associated with disease activity in the investigated patients. Key messages Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
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- Juto, A, et al.
(författare)
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MYELOPEROXIDASE (MPO) POSITIVE EXTRACELLULAR VESICLES (EVS) EXPRESSING COMPLEMENT SPLIT PRODUCTS IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS (AAV)
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1434-1434
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Complement activation has a critical role for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously shown increased expression of complement split products C3a and C5a on myeloperoxidase (MPO) positive EVs (MPO+EVs) in plasma from AAV patients with kidney involvement compared to the patients with non-renal disease and the EV-levels correlated with disease activity (1).ObjectivesTo investigate the expression of a larger set of complement components on circulating MPO+EVs in relation to disease activity and kidney involvement in patients with AAV.MethodsEighty-nine patients with AAV and 23 healthy controls were included. The concentration of MPO+EVs expressing complement split products C3a, C4d, C5a, terminal complement complex-TCC (C5b-9) or complement factor B (CFB) were analyzed from citrate plasma by flow cytometry. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS).ResultsIn the AAV group, there were 47 males (52.8%), the median age was 56 years and 33 (37.1%) patients were anti-MPO-positive and 54 (60.7%) were anti-PR3-positive. Two patients were positive for both antibodies. Median disease duration for patients with active AAV (BVAS>0; n=81) was 4 days and for patients in remission (BVAS 0; n=8) 1259 days. 64% had kidney involvement (n=52). Highly active AAV (BVAS ≥12) was noted in 62 patients, of whom 49 patients had kidney involvement. Active disease (0<BVAS<12) was seen in 19 patients. AAV patients had significantly higher levels of MPO+, MPO+C3a+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p<0.001). Patients in remission had higher levels of MPO+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p≤0.001). There was a significant difference in levels of MPO+(p=0.02), MPO+C3a+(p<0.001), MPO+C4d+(p<0.001) and MPO+TCC+ EVs (p<0.001) in patients with kidney involvement compared with patients without (n=29) (Figure 1). For patients with BVAS>0 there was a weak correlation between MPO+, MPO+C3a+, MPO+C4d+, MPO+TCC+ EVs and BVAS. Kidney biopsies from 34 patients were classified according to histopathological class (2): crescentic (n=6), focal (n=18), mixed (n=6), sclerotic (n=4). The level of MPO+C4d+EVs was higher in the sclerotic type compared to focal (p=0.04, 95% CI [2.4–103.7]) and mixed (p=0.04, 95% CI [1.4–119.1]).ConclusionLevels of EVs expressing complement split products were generally increased in AAV patients and patients with kidney involvement had higher levels of total MPO+EVs exposing C3a, C4d or TCC compared with patients without suggesting a role in kidney AAV pathogenesis. Patients with sclerotic kidney histotype had higher levels of MPO+C4d EVs compared with focal and mixed subgroups pointing to that activation of the classical complement pathway may be of importance in severe forms of kidney AAV.References[1]Antovic A et al. J Rheumatol. 2020 May 1;47(5):714-721. doi: 10.3899/jrheum.181347. Epub 2019 Aug 1. PMID: 31371653.[2]Berden AE et al. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477. Epub 2010 Jul 8. PMID: 20616173.Disclosure of InterestsNone declared
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- Dunn, N, et al.
(författare)
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Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies
- 2018
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:9, s. 1224-1233
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Tidskriftsartikel (refereegranskat)abstract
- Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. Objective: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. Methods: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house–validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records. Results: ADAs were detected in 37% of relapsing–remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive. Conclusion: Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.
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- Alexeyev, O A, et al.
(författare)
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Increased plasma levels of soluble CD23 in haemorrhagic fever with renal syndrome; relation to virus-specific IgE.
- 1997
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Ingår i: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 109:2, s. 351-5
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Tidskriftsartikel (refereegranskat)abstract
- In 15 consecutive patients hospitalized with nephropathia epidemica, a European form of haemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus, plasma concentrations of soluble CD23 (sCD23) and Puumala virus-specific IgE were determined. In the acute phase of illness, 11/15 patients had increased sCD23 levels (> 91 U/ml), whereas in convalescence, values of 8/10 patients were normalized. Maximal sCD23 values were correlated to maximal concentrations of Puumala virus-specific serum IgE (r = 0.597; P = 0.025). The results are compatible with a known ability of sCD23 to augment IgE production.
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| 10. |
- Boremalm, Malin, et al.
(författare)
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Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis
- 2019
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:8, s. 1060-1067
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Methods Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. Results A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. Conclusions In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
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