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Medical University Innsbruck Department of Internal Medicine IV

Andreas Kronbichler, MD Anichstraße 35

6020 Innsbruck Austria

Betreff: Bewerbung um “Projektförderpreis (gesponsert von Pfizer)”

Sehr geehrter Herr Professor Dr. Machold, sehr geehrter Herr Professor Dr. Dejaco, sehr geehrter Herr Dozent Dr. Zwerina! Sehr geehrte Kommissionsmitglieder!

Bitte finden Sie in der Anlage meinen Projektantrag „Biomarkers for the assessment of

disease acitivity in ANCA-associated vasculitides“, den ich hiermit für den ÖGR

„Projektförderpreis (gespondert von Pfizer)“ einreiche. Kurzer Lebenslauf und vollständige

Publikationsliste sowie das bereits eingeholte Ethikvotum der Medizinischen Universität

Innsbruck sind dem Projektantrag beigefügt.

Das hier vorgestellte Projekt findet in Kollaboration mit der Universitätsklinik für Innere Medizin VI an der Medizinischen Universität Innsbruck statt. Zahlreiche Kollaborationen innerhalb Österreichs sollten den interdisziplinären Charakter der Arbeit hervorheben, welche unter der Schirmherrschaft des Arbeitskreises „Vaskulitis und Orphan Diseases“ der ÖGR stattfinden wird.

Das Projekt sollte nach Genehmigung initiiert werden (Beginn: 01/01/2017) und Ende

2017 (Plan 31/12/2017) fertig gestellt werden (inklusive erster „submission“). Die Versuche werden in den Laborräumen der Inneren Medizin in Innsbruck durchgeführt.

Das Einreichen eines Forschungs-Grants (FWF – KLIF) ist zur Deckung der Gesamtkosten

des Projektes bereits in Bearbeitung, die Zuerkennung des „Projektförderpreis“ könnte das Vorankommen des Projektes maßgeblich beschleunigen. Die zusätzlichen Kosten (zu der Fördermenge) wird durch interne Forschungsgelder gedeckt.

Die kollaborierenden AutorInnen erklärten sich mit dem Einreichen des Projektes für den

Förderpreis der ÖGR einverstanden.

Für etwaige Fragen stehe ich Ihnen gerne und jederzeit zur Verfügung.

Hochachtungsvoll!

Andreas Kronbichler, M.D.

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Anlagen: 1x Projektantrag

1x Lebenslauf mit Publikationsliste

1x Ethikvotum

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Abstract:

Background. Studies in anti-neutrophil cytoplasmic antibody (ANCA)-associated

vasculitis have revealed biomarkers distinguishing active disease from remission. We

conducted a systematic literature review to elucidate the potential of these markers in

prediction of disease activity.

Rationale/Aim. We tried to corroborate the abundant expression of the most promising

markers. In our cross-sectional analysis, a biomarker panel comprising CRP and

urinary MCP-1 yielded a sensitivity and specificity of 76% (AUC 0.89). While CRP may

be influenced by gender, atherosclerotic burden or infectious complications, MCP-1 is

a major chemoattractant abundantly regulated in several autoimmune disorders. Thus,

the “best” panel is useless in assessing disease activity in daily routine.

This project aims to investigate novel biomarker candidates, which may hold great

promise in improving this diagnostic dilemma. In addition, we aim to investigate

markers of endothelial dysfunction, tissue injury & remodelling longitudinally which may

allow the prediction of disease relapses and thus would be favourable for daily clinical

routine in the management of these complex patients.

Design. Samples from 30 patients suffering from ANCA-associated vasculitis and large

vessel vasculitis each as well as 20 healthy controls will be followed up/evaluated

prospectively.

Methods. Plasma biomarkers will be measured using commercially available ELISA

kits.

Study period. This study will be initiated on January 1st, 2017. Ethics approval has

already been obtained (see below). We expect submission of a manuscript draft end of

2017.

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Background:

Granulomatosis with polyangiitis (GPA, previously known as Wegener’s

granulomatosis) and microscopic polyangiitis (MPA) are subtypes of primary systemic

vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA). They are

grouped together as ANCA-associated vasculitis, a potentially devastating, relapsing-

remitting autoimmune inflammatory condition present in approximately 10-30 per

100,000 people in Europe [1]. During active disease, endothelial injury and repair play

a pivotal role. Damage of the affected organs leads to a significant morbidity with long-

term complications such as polyneuropathy or impaired kidney function. Minimisation

of relapse risk is one of the major aims in the long-term management of patients with

systemic vasculitides. A lack of biomarkers correlating with the current disease status

is hampering physician’s care by the risk of induction of severe complications in terms

of over-immunosuppression or further organ damage attributable to active vasculitis in

case of inadequate treatment. Current methods to assess disease activity (Birmingham

Vasculitis Activity Score [2] and ANCA [3]) are unreliable in this perspective.

In common with other vasculitis syndromes, endothelial dysfunction as measured by

impaired response to vasodilating agents or Laser-Doppler flowmetry is a key hallmark

in newly diagnosed or relapsing patients. Patients with active disease have an

increased risk to develop venous thromboembolic events with a frequency of

approximately 7 per 100 patient-years, compared to an overall risk of 0.15-0.31 per 100

patient-years in the general population [4]. Moreover, the odds-ratio of cardiovascular

events is 6.7 in ANCA-associated vasculitis compared to the general population [5], an

excess again not accounted for by traditional risk factors but likely to be related to

ongoing chronic inflammation and vasculitis activity sub-optimally controlled in patients.

ANCA-associated vasculitis is associated with accelerated atherosclerosis [5], arterial

stiffness [6], diffuse endothelial dysfunction [7] and reduced nitric oxide bioavailability.

Improving the cardiovascular morbidity and mortality is one of the unmet needs in the

management of patients with ANCA-associated vasculitis. Novel immunosuppressive

agents have been licensed for the treatment of active ANCA-associated vasculitis, such

as rituximab [8], but its effects on vascular function has yet to be determined. We are

currently participating in a trial comparing the effects of this monoclonal antibody

directed against CD20 bearing cells on vascular dysfunction to a cyclophosphamide-

based induction therapy. Preliminary results from this observational study presented in

abstract form favour rituximab in terms of improving endothelial dysfunction (Casian A

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et al., Rituximab and Vascular Function in ANCA Associated Vasculitis, 17th Vasculitis

Workshop, London 2015).

Biomarkers are representing potential candidates to improve diagnostic accuracy and

disease activity assessment. In the last decade several large scale biomarker studies

have been conducted to identify an ideal blood biomarker reflecting general disease

activity and urinary biomarkers were studied to elucidate disease activity in patients

with renal involvement. Lally et al. highlighted that biomarkers are needed to guide the

management of patients with ANCA-associated vasculitis [9]. In addition, the authors

recommended that further insights into aetiopathogenesis (especially using “-omic”

approaches) are needed to develop improved diagnostic tools (i.e. in combination with

biomarkers).

In a first attempt, we performed a systematic review of the literature on to date

published biomarkers, calculated a fold-change expression (see Table 1) and

performed a validation study in a cross-sectional cohort of well phenotyped patients.

Moreover, the aim of our study was to establish a reliable biomarker panel reflecting

disease activity.

Order of Expression

Active Versus Remission

(Overall Fold-change)

Disease

Class

sC5bC9 263.65 AAV Urine

Complement C3a 162.5 AAV Urine

GM-CSF 23.59 AAV Inflammation

CRP 23.3 MPA Inflammation

Complement C5a 19.06 AAV Urine

Soluble Flt-1 17.03 GPA Vascular I&R

CRP 12.18 GPA Inflammation

CRP 11.83 AAV Inflammation

Complement Bb 11.00 AAV Urine

IL-17A 10.88 AAV Inflammation

Complement C5a 9.59 AAV Inflammation

MCP-1 9.18 AAV Urine

Soluble Flt-1 8.52 MPA Vascular I&R

Hyaluronan 8.17 AAV Metabolism

Complement C3a 8.11 AAV Inflammation

IL-18 bp 7.95 AAV Inflammation

Table 1. Biomarkers with the highest difference between active and inactive disease are depicted together;

along with the respective disease (either GPA or MPA or both entities together summarised as AAV) and

the arbitrary class. Abbreviations: AAV (anti-neutrophil cytoplasm antibody-associated vasculitis), CRP

(C-reactive protein), Flt-1 (Fms-like tyrosine kinase-1), GM-CSF (granulocyte macrophage

colony-stimulating factor), GPA (granulomatosis with polyangiitis), IL-17A (interleukin-17A), IL-18 bp

(interleukin-18 binding protein), MCP-1 (monocyte chemotactic protein-1), MPA (microscopic

polyangiitis), Vascular I&R (vascular injury and repair).

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In our cross-sectional analysis, CRP, complement C3a and C5a, IL-18 bp, urinary

MCP-1 and C5a showed significantly higher expression levels in active AAV compared

to inactive patients (all P≤0.01). Using Salford Predictive Modeling software, the most

significant independent predictors and cut-off points for active disease were as follows:

MCP1-levels in urine and CRP levels. Together, these two biomarkers yielded a

sensitivity and specificity of 76%. The receiving operator curve (ROC) reached a level

of 0.89 (Figure 1, Kronbichler A, Nephrol Dial Transplant 2016; 31:930-6).

Figure 1. Using Salford Predictive Modeling software, the most significant independent predictors and cut-

off points for active renal disease were as follows: MCP-1 levels in urine > 0.53 ng/ml and CRP levels >

21.6 mg/l. Adding these two biomarkers sensitivity was 76 % and specificity was 76 %. The ROC curve

reached a level of 0.89.

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Project Aim / Research Rationale:

There is a clear need to extend our knowledge regarding biomarker expression in

ANCA-associated vasculitides. In a preliminary set of experiments, we performed a

proteomic approach to investigate potential future biomarker targets. We could

elucidate an abundant expression of transport proteins, such as haptoglobin, which was

32-fold over-expressed in patients with active ANCA-associated vasculitis compared to

patients in remission (see Table 2). Since proteomic analyses are not reliable for daily

routine investigations, other technical methods, such as protein detection using ELISA

kits are more appropriate.

The main aims of the underlying project are

a) to corroborate the findings of the preliminary proteomic approach

b) to evaluate further potential candidates, which might not be detected by classic mass

spectrometry methods

c) to find an ideal biomarker panel associated with the disease activity state

d) to test this panel in a subset of relapsing patients

The validity of these investigations should be confirmed in further larger follow-on

investigations. Little is known regarding expression of these candidates in vasculitides

per se. Elevated haptoglobin levels have been reported in vasculitis patients (GPA,

along with patients suffering from giant cell arteritis and Takayasu arteritis). In addition,

in vitro experiments demonstrated that haptoglobin induced angiogenesis, correlated

with disease and angiogenic activity and was partially inhibited by antibodies directed

against haptoglobin in sera from patients. It was hypothesised that haptoglobin may

actively participate in tissue repair by stimulating neo-angiogenesis in vasculitis [10].

Several other proteins of interest were identified through our preliminary results. Among

the most promising candidates, which are involved in cardiovascular disorders, are

Lectin-like oxidized low-density lipoprotein receptor 1 (Lox-1), Lipoprotein-associated

phospholipase A2 (Lp-PLA2), asymmetric dimethylarginine (ADMA) and endoglin

(CD105). Moreover, classic growth factors contributing to neo-angiogenesis in tumour

cells, which is also a hallmark of vasculitis, will be included in our analysis, including

platelet derived growth factor-BB (PDGF-BB) and hepatocyte growth factor (HGF). A

novel marker of inflammation, supporting neutrophil trafficking, represents Midkine [11].

This is of particular interest, since neutrophils play a pivotal role in AAV and neutrophil

infiltration of endothelial cells is one important step initiating inflammation. Monach and

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colleagues have studied matrix metalloproteinase expression extensively, but did not

investigate their marker of interest during disease relapse [12]. We would study these

markers, namely MMP-3, TIMP-1 and CXCL13, along with the identified markers in our

preliminary experiments (talin-1 and vinculin) in a set of well selected patients.

Serum levels of these biomarkers will be measured using an enzyme-linked

immunosorbent assay (ELISA). The expression of biomarkers will be measured during

an active disease state (prior to initiation of specific immunosuppressive measures,

such as cyclophosphamide or rituximab), during remission (sample collection, 6 months

post first collection) prior to and at the time of relapse. Moreover, we plan to include

two comparator groups, consisting of a) patients with large vessel vasculitides (giant

cell arteritis and Takayasu arteritis), having signs of systemic inflammation combined

with endothelial dysfunction, and b) healthy age-matched controls.

Table 2. Preliminary results (derived from a proteomic approach).

This design will allow the following comparisons (Figure 2):

1. F vs G: cases vs controls at relapse 2. F/C vs G/D: change from remission to relapse between cases and controls 3. F vs E: to assess whether markers of relapse change before relapse becomes clinically

apparent 4. Analysis of A and B will permit a secondary assessment of the extent to which markers

of relapse may also identify de novo disease.

Figure 2. Different analysis strategies are depicted.

Our aim is to analyse 30 samples of patients with ANCA-associated vasculitis

during active disease, during remission, prior to and at the time of relapse. Moreover,

Marker Fold-change (active versus remission)

Haptoglobin 32.00

á1-Actin (cardiac muscle-1) 10.00

Talin-1 10.00

Vinculin 6.00

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a similar proportion of samples from patients with large vessel vasculitides should be

collected. We expect to finish sample collection until mid of 2017.

We recognise that, for biomarker discovery, large sample sizes are desirable. The

sample size for the present study is determined by the estimated difference of marker

expression comparing active disease to remission (3-fold difference, respective power

of 85%). Although the number of relapse samples might be lower, this pilot trial will

allow concrete calculation of follow-up studies. We expect to apply for samples

collected from the PEXIVAS trial, which is currently ongoing and aims to recruit

approximately 700 patients to perform further biomarker studies. Clearly, our aim is to

apply to another funding body once this pilot trial is finished.

Study Hypothesis:

1) We hypothesise that markers of angiogenesis, tissue injury and repair are useful in

the differentiation of diverse disease activity states and the prediction of disease

relapse in patients with ANCA-associated vasculitis.

2) We hypothesise to propose a biomarker panel, which will replace currently used

biomarkers, including ANCA.

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Materials and Methods

ELISA

ELISA kits of the proposed markers of interest are commercially available. Protein

content of samples will be analysed in duplicates according to manufacturer’s protocol.

Statistical analysis

Statistical analysis will be done with IBM SPSS Statistics for Windows, Version 21.0.

Spearman´s rank correlation coefficient will be used to test statistical dependence

between possible AAV marker proteins and age. Means of duplicates will be analysed

by descriptive statistics followed by independent-samples t-test or Wilcoxon test,

respectively. In addition Kaplan-Meier survival will be shown for each test group.

Collaborations

Department of Internal Medicine IV (Nephrology and Hypertension), Medical University

of Innsbruck, Innsbruck, Austria (Andreas Kronbichler*, Johannes Leierer, Gert Mayer)

Department of Internal Medicine VI (Rheumatology), Medical University of Innsbruck,

Innsbruck, Austria (Christina Duftner*, Michael Schirmer*)

Department of Rheumatology, Medical University Graz, Graz, Austria (Christian

Dejaco*)

Department of Internal Medicine III (Rheumatology), University Hospital Jena, Jena,

Germany (Thomas Neumann)

1. Medical Department, Hanusch Hospital Vienna (Jochen Zwerina*)

*Current members of the Austrian Society of Rheumatology and Rehabilitation

Resources and Cost Calculation

Infrastructure

All necessary instruments are ready to use in the laboratory spaces used by the

rheumatology and nephrology department.

Cost Calculation

Consumables Support requested (amounts in €)

Month-

Month/2016- 2017

(Year)

Month-Month/2017

(Year)

Total

28 ELISA Kits (á 700€) 18.900

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1 Consumable 1.300

Total 1.300 18.900 20.200*

* Additional expenses will be covered by internal financial possibilities

(“leistungsorientierte Forschung”)

Time frame

01-01-2017 Project start date

01-02-2017 Completion of sample collection

01-04-2017 Performance of the respective ELISA analysis

01-05-2017 Statistical analysis of the results obtained

01-09-2017 Preparation of the publication

01-12-2017 Submission of the manuscript (final publication until “close-out

date” 01-03-2018), published in a peer-reviewed journal

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Ethical considerations

A positive evaluation has already been obtained (number: AN2014-0089 335/4.6) from

the Medical University of Innsbruck (see attached file)

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Referenzen:

1. Watts RA, Lane S, Scott DG. What is known about the epidemiology of the vasculitides? Best Pract Res Clin Rheumatol 2005;19(2):191-207 2. Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87(11):671-678 3. Tomasson G, Grayson PC, Mahr AD, et al. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis--a meta-analysis. Rheumatology (Oxford) 2012;51(1):100-109 4. Monach PA. ANCA-associated vasculitis: a prothrombotic state even in remission? J Rheumatol 2013;40(12):1935-1937 5. de Leeuw K, Sanders JS, Stegeman C, et al. Accelerated atherosclerosis in patients with Wegener's granulomatosis. Ann Rheum Dis 2005;64(5):753-759 6. Booth AD, Wallace S, McEniery CM, et al. Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum 2004;50(2):581-588 7. Booth AD, Jayne DR, Kharbanda RK, et al. Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 2004;109(14):1718-1723 8. Kronbichler A, Jayne DR. Con: Should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab? Nephrol Dial Transplant 2015;30(7):1075-1081 9. Lally L, Spiera RF. Biomarkers in ANCA-associated vasculitis. Curr Rheumatol Rep 2013;15(10):363 10. Cid MC, Grant DS, Hoffman GS, et al. Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. J Clin Invest 1993;91(3):977-985 11. Muramatsu T, Kadomatsu K. Midkine: an emerging target of drug development for treatment of multiple diseases. Br J Pharmacol 2014;171(4):811-813 12. Monach PA, Warner RL, Tomasson G, et al. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis 2013;72(8):1342-1350

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CURRICULUM VITAE

September 2016

NAME

Andreas KRONBICHLER Medical University of Innsbruck Internal Medicine IV (Nephrology and Hypertension)

Anichstraße 35

6020 Innsbruck (Austria)

POSITION TITLE

Department of Internal Medicine, Specialty Registrar in Renal Medicine, Medical University Innsbruck

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,

and include postdoctoral training.)

INSTITUTION AND LOCATION DEGREE

(if applicable)

YEAR(s) FIELD OF

STUDY

Medical University Innsbruck M.D. 2010 Medicine

Medical University Innsbruck PhD 2013-ongoing

PROFESSIONAL EXPERIENCE

Positions and employments

2010-2011 Internship and Residency, Departments of Medicine (various), University of

Jena, Germany

2011-2014 Internship and Residency, Departments of Medicine (various), Medical

University Innsbruck, Austria

2014-2015 Clinical Fellowship, Honorary Research Fellow, Addenbrooke’s Hospital,

Vasculitis and Lupus Clinic, University of Cambridge, United Kingdom

2015-present Internship and Residency, Departments of Medicine (various), Medical

University Innsbruck, Austria

Other professional experiences

2015-2016 Guest Editor BioMed Research International (‘Focal Segmental

Glomerulosclerosis: Genetics, Mechanism, and Therapies’)

2016-2017 Guest Editor BioMed Research International (‘Nephrotic Syndrome:

Genetics, Mechanism, and Therapies’)

SCIENTIFIC SOCIETIES Member of the “European Vasculitis Study Group (EUVAS)” Member of the “Lupus Nephritis Trial Network (LNTN)” Member of the “European Renal Association-European Dialysis and Transplantation

Association (ERA-EDTA)” Member of the “Immunonephrology Working Group (IWG, ERA-EDTA)” Member of the “Austrian Society of Nephrology (ÖGN)”

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Member of the “Austrian Society of Rheumatology (ÖGR)” Member of the “Austrian Society of Internal Medicine (ÖGIM)” SELECTED PUBLICATIONS (from year 2009 onwards)

1. Schramek H, Sarközi R, Lauterberg C, Kronbichler A, Pirklbauer M, Albrecht R, Noppert SJ, Perco P, Rudnicki M, Strutz FM, Mayer G. Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells. Lab Invest 2009; 89:1304-16.

2. Sarközi R, Hauser C, Noppert SJ, Kronbichler A, Pirklbauer M, Haller VM, Grillari J, Grillari-Voglauer R, Mayer G, Schramek H. Oncostatin M is a novel inhibitor of TGF-{beta} 1-induced matricellular protein expression. Am J Physiol Renal Physiol 2011; 301:F1014-25.

3. Kronbichler A, Mayer G. Renal involvement in autoimmune connective tissue diseases. BMC Medicine 2013, 11:95.

4. Kronbichler A, König P, Busch M, Wolf G, Mayer G, Rudnicki M. Rituximab in adult patients with multi-relapsing/steroid-dependent minimal change disease and focal segmental glomerulosclerosis: a report of 5 cases. Wien Klin Wochenschr 2013; 125:328-33.

5. Neuwirt H, Kronbichler A. Dabigatran pharmacokinetics-implications for treatment. Am J Kidney Dis 2013; 62:180.

6. Welzl K, Weinberger B, Kronbichler A, Sturm, G, Kern G, Mayer G, Grubeck-Loebenstein B, Koppelstaetter C. How immunosuppressive therapy affects T cells from kidney transplanted patients of different age: the role of latent CMV infection. Clin Exp Immunol 2014; 176:112-9.

7. Kronbichler A, Kerschbaum J, Rudnicki M. Induction regimens for ANCA-Associated Vasculitis. N Engl J Med 2013; 369:1864.

8. Kronbichler A, Oelzner P, Syrbe G, Lopatta E, Wolf G, Neumann T. Bilateral pulmonary embolism in twins with PAI-1 4G/5G gene polymorphism: a case report. Wien Klin Wochenschr 2014; 126:53-5.

9. Kronbichler A, Mayer G. Nephrotic syndrome; is rituximab the light at the end of the tunnel in the treatment of adult steroid-dependent minimal change disease and focal segmental glomerulosclerosis? J Nephropathol 2014; 3:1-3.

10. Kronbichler A, Kerschbaum J, Fernandez-Fresnedo G, Hoxha E, Kurschat CE, Busch M, Bruchfeld A, Mayer G, Rudnicki M. Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis: A systematic review. Am J Nephrol 2014; 39:322-330.

11. Kronbichler A. Boon and bane of remission induction with rituximab in ANCA-associated vasculitis: lessons learned from the RAVE-ITN follow-up study. J Renal Inj Prev 2013; 3:9-10.

12. Kronbichler A, Bruchfeld A. Rituximab in Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis. Nephron Clin Pract 2014;128(3-4):277-82.

13. Kronbichler A, Frank R, Kirschfink M, Szilagyi A, Csuka D, Prohaszka Z, Schratzberger P, Lhotta K, Mayer G. Efficacy of eculizumab in a patient with immunoadsorption-dependent catastrophic antiphospholipid syndrome: a case report. Medicine 2014; 93:e143.

14. Kronbichler A, Jayne DR. Con: Should all patients with ANCA-associated vasculitis be primarily treated with rituximab? Nephrol Dial Transplant 2015; 30:1075-81.

15. Kronbichler A, Jayne DR. Opponent’s comments. Nephrol Dial Transplant 2015; 30:1087-8.

16. Kronbichler A, Jayne DRW, Mayer G. Frequency, Risk Factors and Prophylaxis of Infection in ANCA-Associated Vasculitis. Eur J Clin Invest 2015;45(3):346-68.

17. Shin JI, Kronbichler A. Rituximab for patients with nephrotic syndrome. Lancet 2015; 385:225-6.

18. Kronbichler A, Kerschbaum J, Mayer G. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review. J Immunol Res. 2015; 2015:858027.

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19. Kronbichler A, Gut N, Zwerina J, Neuwirt H, Rudnicki M, Mayer G. Extending the spectrum of a chameleon: IgG4-related disease appearing as interstitial nephritis and mimicking anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatology 2015; 54:1936-8.

20. Kronbichler A, Brezina B, Quintana LF, Jayne DRW. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev 2016; 15(1):38-49.

21. Kronbichler A, Gründlinger G, Kerschbaum J, Leierer J, Mayer G, Rudnicki M. Evaluation and Validation of Biomarkers in ANCA-Associated Vasculitis. Nephrol Dial Transplant 2016, 31:930-6.

22. Rudnicki M, Perco P, D’haene B, Leierer J, Heinzel A, Mühlberger I, Sunzenauer J, Regele H, Kronbichler A, Mestdagh P, Vandesompele J, Mayer B, Mayer G. An integrative analysis of renal miRNA- and mRNA-expression signatures in progressive chronic kidney disease. Eur J Clin Invest 2016; 46:213-26.

23. Kronbichler A, Leierer J, Oh J, Meijers B, Shin JI. Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis. Biomed Res Int 2016;2016:2150451.

24. Beer A, Mayer G, Kronbichler A. Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades. Biomed Res Int 2016;2016:4192578.

25. Kim SH, Park SJ, Han KH, Kronbichler A, Saleem MA, Oh J, Lim BJ, Shin JI. Pathogenesis of minimal change nephrotic syndrome: an immunological concept. Korean J Pediatr 2016; 59:205-11.

26. Kronbichler A. Herzinfarkt nach Rituximab: Zusammenhang nicht ausgeschlossen. Dtsch Med Wochenschr 2016; 141:846.

27. Kronbichler A, Oh J, Meijers B, Shin JI. Focal Segmental Glomerulosclerosis: Genetics, Mechanism, and Therapies. Biomed Res Int 2016; 2016:9643785.

28. Kronbichler A, Saleem MA, Meijers B, Shin JI. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View. J Immunol Res 2016; 2016:2068691.

29. Kronbichler A, Neumann I, Mayer G. Moderator’s view: the use of calcineurin inhibitors in the treatment of lupus nephritis. Nephrol Dial Transplant 2016 Sep 1. Pii: gfw288.

AWARDS ERA-EDTA Long-Term Fellowship (LTF) 08/2014 – 07/2015

RESEARCH GRANTS

NIHR BRC Immunity, Infection and Inflammation (Main Applicant, £14.000, 03/2015-

08/2015), ‘Composition of the human microbiome in granulomatosis with polyangiitis: A

pilot study’

Addenbrooke’s Charitable Trust (Co-Applicant, £18.937, 07/2015-06/2016), ‘Quantitative

proteomics by SWATH MS identifies the role of complement, cytokines and chemokines in

the pathogenesis of PR3-ANCA positive vasculitis’

Arthritis Research UK (Co-Applicant, £290.430,64, 01/2016-01/2018), ‘The significance of

Staphylococcus aureus carriage and granulomatosis with polyangiitis: Pathophysiological

alterations unraveled’