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Featured researches published by Maria Weiner.


Clinical Journal of The American Society of Nephrology | 2015

Outcome and Treatment of Elderly Patients with ANCA-Associated Vasculitis

Maria Weiner; Su Mein Goh; Aladdin J. Mohammad; Zdenka Hruskova; Anisha Tanna; Annette Bruchfeld; Daina Selga; Zdenka Chocova; Kerstin Westman; Per Eriksson; Charles D. Pusey; Vladimir Tesar; Alan D. Salama; Mårten Segelmark

BACKGROUND AND OBJECTIVES ANCA-associated vasculitis is commonly found in elderly patients, but there are few data concerning outcome and treatment in the highest age groups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Consecutive patients (N=151) presenting between 1997 and 2009 were retrospectively included from local registries in six centers in Sweden, the United Kingdom, and the Czech Republic if diagnosed with microscopic polyangiitis or granulomatosis with polyangiitis at age ≥75 years during the study period. Patients were followed until 2 years from diagnosis or death. Data on survival and renal function were analyzed with respect to age, sex, ANCA specificity, renal function, C-reactive protein, comorbidities, and Birmingham Vasculitis Activity Score at diagnosis as well as treatment during the first month. RESULTS Median follow-up was 730 days (interquartile range, 244-730). Overall 1-year survival was 71.5% and 2-year survival was 64.6%. Older age, higher creatinine, and lower Birmingham Vasculitis Activity Score were associated with higher mortality in multivariable analysis. Patients who were not treated with standard immunosuppressive therapy had significantly worse survival. Renal survival was 74.8% at 1 year. No new cases of ESRD occurred during the second year. High creatinine at diagnosis was the only significant predictor of renal survival in multivariable analysis. CONCLUSIONS ANCA-associated vasculitis is a disease with substantial mortality and morbidity among elderly patients. This study showed a better prognosis for those who received immunosuppressive treatment and those who were diagnosed before having developed advanced renal insufficiency.


Autoimmunity Reviews | 2016

The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)

Maria Weiner; Mårten Segelmark

Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up.


Kidney International | 2017

Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients

Stephen P. McAdoo; Anisha Tanna; Zdenka Hruskova; Lisa Holm; Maria Weiner; Nishkantha Arulkumaran; Amy Kang; Veronika Satrapová; Jeremy Levy; Sophie Ohlsson; Vladimir Tesar; Mårten Segelmark; Charles D. Pusey

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such ‘double-positive’ cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.


Clinical and Experimental Immunology | 2014

A myelopoiesis gene signature during remission in anti‐neutrophil cytoplasm antibody‐associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy

Tino Kurz; Maria Weiner; Camilla Skoglund; S. Basnet; Per Eriksson; Mårten Segelmark

A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti‐neutrophil cytoplasm antibody‐associated vasculitis (AAV), and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors [CCAAT/enhancer binding protein α (CEBP‐α), CCAAT/enhancer binding protein β (CEBP‐β), SPI1/PU.1‐related transcription factor (SPIB), spleen focus forming virus proviral integration oncogene, PU.1 homologue (SPI1)] and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were analysed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMC, PMN) and MPO (PBMC). PR3 and SPIB mRNA correlated positively in controls but negatively in patient PBMC. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses, but correlated with steroid treatment. Prednisolone doses were negatively linked to SPIB and miR‐155‐5p, miR‐339‐5p (PBMC) and to miR‐221, miR‐361 and miR‐505 (PMN). PR3 mRNA in PBMC correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multi‐factorial, but to an important extent explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.


Nephrology Dialysis Transplantation | 2014

Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden

Aladdin J. Mohammad; Maria Weiner; Christopher Sjöwall; Martin Johansson; Anders Bengtsson; Christina Ståhl-Hallengren; Ola Nived; Per Eriksson; Gunnar Sturfelt; Mårten Segelmark

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.


Clinical and Experimental Immunology | 2014

A myelopoiesis gene signature during remission in ANCA associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy

Tino Kurz; Maria Weiner; Camilla Skoglund; Sandeep Basnet; Per Eriksson; Mårten Segelmark

A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti‐neutrophil cytoplasm antibody‐associated vasculitis (AAV), and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors [CCAAT/enhancer binding protein α (CEBP‐α), CCAAT/enhancer binding protein β (CEBP‐β), SPI1/PU.1‐related transcription factor (SPIB), spleen focus forming virus proviral integration oncogene, PU.1 homologue (SPI1)] and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were analysed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMC, PMN) and MPO (PBMC). PR3 and SPIB mRNA correlated positively in controls but negatively in patient PBMC. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses, but correlated with steroid treatment. Prednisolone doses were negatively linked to SPIB and miR‐155‐5p, miR‐339‐5p (PBMC) and to miR‐221, miR‐361 and miR‐505 (PMN). PR3 mRNA in PBMC correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multi‐factorial, but to an important extent explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.


Nephrology Dialysis Transplantation | 2018

Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

Maria Weiner; Rune Bjørneklett; Zdenka Hruskova; Bruce Mackinnon; Caroline J. Poulton; Leo Sindelar; Aladdin J. Mohammad; Per Eriksson; Loreto Gesualdo; Duvuru Geetha; Matija Crnogorac; David Jayne; Susan L. Hogan; Colin C. Geddes; Vladimir Tesar; Knut Aasarød; Mårten Segelmark

Background In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); P < 0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO:PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.


Clinical and Experimental Immunology | 2014

A myelopoiesis gene signature during remission in anti-neutrophil cytoplasm antibody-associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy: Prednisolone and myelopoiesis genes in AAV

Tino Kurz; Maria Weiner; Camilla Skoglund; S. Basnet; Per Eriksson; Mårten Segelmark

A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti‐neutrophil cytoplasm antibody‐associated vasculitis (AAV), and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors [CCAAT/enhancer binding protein α (CEBP‐α), CCAAT/enhancer binding protein β (CEBP‐β), SPI1/PU.1‐related transcription factor (SPIB), spleen focus forming virus proviral integration oncogene, PU.1 homologue (SPI1)] and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were analysed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMC, PMN) and MPO (PBMC). PR3 and SPIB mRNA correlated positively in controls but negatively in patient PBMC. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses, but correlated with steroid treatment. Prednisolone doses were negatively linked to SPIB and miR‐155‐5p, miR‐339‐5p (PBMC) and to miR‐221, miR‐361 and miR‐505 (PMN). PR3 mRNA in PBMC correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multi‐factorial, but to an important extent explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.


Rheumatology | 2017

WS7_1 Organ Damage and Hospitalization in Elderly Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

Maria Weiner; Su Mein Goh; Aladdin J. Mohammad; Zdenka Hruskova; Anisha Tanna; Phoebe Sharp; Amy Kang; Annette Bruchfeld; Daina Selga; Zdenka Chocova; Kerstin Westman; Per Eriksson; Lorraine Harper; Charles D. Pusey; Vladimír Tesaŕ; Alan D. Salama; Mårten Segelmark


Clinical and Experimental Rheumatology | 2015

Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody associated vasculitis from healthy controls.

Camilla Skoglund; Anting Liu Carlsen; Maria Weiner; Tino Kurz; Thomas Hellmark; Per Eriksson; Niels H. H. Heegaard; Mårten Segelmark

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Tino Kurz

Linköping University

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Anisha Tanna

Imperial College London

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Annette Bruchfeld

Karolinska University Hospital

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