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​List of publications

Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study. Chinoy H, Adimulam S, Marriage F, New P, Vincze M, Zilahi E, Kapitány A, Gyetvai A, Ekholm L, Novota P, Remakova M, Charles P, McHugh NJ, Padyukov L, Alfredsson L, Vencovsky J, Lundberg IE, Danko K, Ollier WE, Cooper RG.
Ann Rheum Dis. 2011 Dec 20.


OBJECTIVES: HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM.
METHODS: IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation.
RESULTS: 557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p <0.0001).
CONCLUSION: Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.
FULL ARTICLE: HLA & smoking in IIM

Interrater reliability and aspects of validity of the myositis damage index
Shabina M Sultan, Elizabeth Allen, Robert G Cooper, Sangita Agarwal, Patrick Kiely,
Chester V Oddis, Jiri Vencovsky, Ingrid E Lundberg, Maryam Dastmalchi,
Michael G Hanna, David A Isenberg
Ann Rheum Dis 2011;70:1272–1276.

OBJECTIVES: To test the interrater reliability, internal consistency and aspects of validity of the myositis damage index (MDI) in the assessment of damage in adult patients with idiopathic infl ammatory myopathy (IIM).
METHODS: 95 patients were assessed in six centres as part of this cross-sectional international study. Two parts of a MDI were used to assess disease damage, the MDI and the myositis damage score (MYODAM). The myositis disease activity assessment tool (MDAAT) was used to assess disease activity. Interrater reliability was assessed using intraclass correlation coeffi cient (ICC). Spearman’s rank correlation coeffi cient was used to measure the convergent validity of cross-sectional scores between the two parts of the damage tool and to determine the correlation between the respective components of the
damage and activity tools.
RESULTS: In general, the damage index appears to have good interrater reliability for most of the systems with an ICC greater than 0.65. Convergent validity between the two parts of the damage tool showed good correlation for the individual organ systems (r>0.8). There were weak correlations between some parts of the MDI and corresponding components of the MDAAT.
CONCLUSION: The MDI is a comprehensive tool to assess damage in patients with myositis. With physician education and emphasis to record items that have been
diagnosed since the myositis diagnosis, the MDI will provide a valuable tool to assess damage in future clinical trials and longitudinal studies.
FULL ARTICLE: Myositis damage index

193rd ENMC International workshop Pathology diagnosis of idiopathic inflammatory myopathies 30 November – 2 December 2012, Naarden, The Netherlands
Jan L. De Bleecker, Ingrid E. Lundberg, Marianne de Visser, for the ENMC Myositis Muscle Biopsy Study Group
Neuromuscular Disorders 23 (2013) 945–951

FULL ARTICLE: Pathology diagnosis of IIM

Anti-PL-7 (Anti-Threonyl-tRNA Synthetase) Antisynthetase Syndrome
Clinical Manifestations in a Series of Patients From a European Multicenter Study (EUMYONET) and Review of the Literature
Ane Labirua-Iturburu, Albert Selva-O’Callaghan, Melinda Vincze, Katalin Danko, Jiri Vencovsky, Benjamin Fisher, Peter Charles, FRCPath, FIBMS, Maryam Dastmalchi, and Ingrid E. Lundberg
Medicine Volume 91, Number 4, July 2012

Autoantibodies against several aminoacyl-transfer-RNA synthetases have been described in patients with myositis; anti-threonyltRNA synthetase (anti-PL-7) is one of the rarest.We describe the clinical and laboratory characteristics of a cohort of European anti-PL-7 patients, and compare them with previously reported cases. This multicenter study
of patients positive for anti-PL-7, identified between 1984 and 2011, derives from the EUMYONET cohort. Clinical and serologic datawere obtained by retrospective laboratory and medical record review, and statistical analyses were performed with chi-squared and Fisher exact tests. Eighteen patients, 15 women, were anti-PL-7 antibody positive. Median follow-up was 5.25 years (interquartile range, 2.8Y10.7 yr), and 4 patients died. All Patients had myositis (12 polymyositis, 5 dermatomyositis, and 1 amyopathic dermatomyositis), 10 (55.6%) had interstitial lung disease, and 9 (50%) had pericardial effusion. Occupational exposure to organic/inorganic particles was more frequent in patients with interstitial lung disease than in the remaining patients (5 of 10 vs. 1 of
7; p = 0.152), although the difference was not significant. Concurrent autoantibodies against Ro60 and Ro52 were seen in 8 of 14 (57%) patients studied. In the literature review the most common manifestations of anti-PL-7 antisynthetase syndrome were interstitial lung disease (77%), myositis (75%), and arthritis (56%). As in other subsets
of the antisynthetase syndrome, myositis and interstitial lung disease are common features of the anti-PL-7 antisynthetase syndrome. In addition, we can add pericarditis as a possible manifestation related to anti-PL-7 antibodies.
FULL ARTICLE: Clinical Manifestations review of litterature

Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or
anti-Ro52/anti-Ro60 autoantibodies
Olga Kryštůfková1, Sevim Barbasso Helmers, Paulius Venalis, Vivianne Malmström, Eva Lindroos, Jiří Vencovský and Ingrid E Lundberg
Arthritis Research & Therapy 2014, 16:454

INTRODUCTION: Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive
myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers.
METHODS: Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were
assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1).
RESULTS: BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B
and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08).
CONCLUSIONS: The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.
FULL ARTICLE: BAFF receptors in muscle tissue of myositis patients

Genotyping of immune-related genetic variants identifies TYK2 as a novel associated locus for idiopathic inflammatory myopathies
M Jani, J Massey, L R Wedderburn, J Vencovský, K Danko, I E Lundberg, L Padyukov, A Selva-O’Callaghan, T Radstake, H Platt9, R B Warren, C E Griffiths, A Lee, P K Gregersen, F W Miller, W E Ollier, R G Cooper, H Chinoy, J A Lamb9, and EUMYONET
Ann Rheum Dis. 2014 September ; 73(9): 1750–1752

FULL ARTICLE: Genotyping of immune-related genetic variants identifies TYK2 as a novel associated locus for IIM

Gene-Gene and Gene-Environment Interactions in Defining Risk and Spectrum of Phenotypes in Idiopathic Inflammatory Myopathies
Robert G Cooper, Hector Chinoy and Ingrid E. Lundberg
Book chapter L. Padyukov (Ed): Between the Lines of Genetic Code. DOI:
© 2014 Elsevier Inc.
FULL CHAPTER: Gene-Gene and Gene-Environment Interactions in IIM

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