Team Leonid Padyukov

Genetics of autoimmune diseases

Introduction

Leonid Padyukov’s research is focused on the risk and course of autoimmune diseases, and ultimately on finding the mechanisms of development of autoimmune diseases. Specifically, the work being done within Leonid’s group has three major directions:

  1. Genetic association studies of inflammatory and autoimmune diseases, including disease subgroups.
  2. Gene-gene and gene-environment interaction studies in autoimmune diseases.
  3. Functional genetic and genomic studies of inflammatory and immune phenotypes.

 

Major research focus

Human complex diseases characterized by involvement of both environmental and genetic factors with important contribution from gene-gene and gene-environmental interactions. The pathways of many of diseases of this type are influenced through immunological mechanisms, e.g. inflammation. We like to understand how genetic variations influence development and/or protection from human common complex autoimmune and inflammatory diseases.

To determine genetic components of the disease we perform analyses of genetic markers in several loci shown to be linked or associated with this disease, e.g. by genome wide association studies, dense mapping of the locus or re-sequencing. Rheumatoid arthritis, idiopathic myositis, SLE, IgA nephropathy, asthma, MCTD and multiple sclerosis are subjects of our investigations during last years. We pay special attention to the functionally important genetic markers, which may affect the structure of the molecule or may regulate important functions. We perform functional genetic studies using DNA methylation, mRNA, and protein expression analysis.

Interference of common genetic variations with splicing mechanisms is one of our focuses in functional genetics and such mechanisms is obvious background for gene-environment interaction.

Copy number variations, haplotype analysis and population genetics are also in the area of our expertise, which gives us an ability to extend the role of established genetic factors to different ethnical groups and populations. Integration of genetics, genomics, epigenetics and proteomics is in our agenda in study of disease susceptibility and pharmacogenomics of RA, specifically in relation to MTX and anti-TNF treatment.

Our research strategy is to combine a translational approach with basic science using analysis of clinical material from available biobank and exploring new bioinformatics tools.

Team Padyukov
Team Padyukov Foto: Leonid Padyukov

Team members

Barbro Larsson, Laboratory Assistant, CMM L8:O4

Lina Marcela Diaz, Assistent Professor, CMM L8:O5

Natalia Rivera, Assistent Professor, CMM L8:O5

Niyaz Yoosuf, Postdoc, CMM L8:O5

Åsa Hedman, Postdoc, CMM L8:O5

Zaihua Zhu, Postdoc, CMM L8:O4

Anna Dzebisashvili, visiting researcher, CMM L8:O5

key publications

A Gene-Environment Interaction Between Smoking and Gene polymorphisms Provides a High Risk of Two Subgroups of Sarcoidosis.
Rivera NV, Patasova K, Kullberg S, Diaz-Gallo LM, Iseda T, Bengtsson C, Alfredsson L, Eklund A, Kockum I, Grunewald J, Padyukov L
Sci Rep 2019 12;9(1):18633

Systematic approach demonstrates enrichment of multiple interactions between non-HLA risk variants and HLA-DRB1 risk alleles in rheumatoid arthritis.
Diaz-Gallo LM, Ramsköld D, Shchetynsky K, Folkersen L, Chemin K, Brynedal B, Uebe S, Okada Y, Alfredsson L, Klareskog L, Padyukov L
Ann Rheum Dis 2018 10;77(10):1454-1462

T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients.
Houtman M, Ekholm L, Hesselberg E, Chemin K, Malmström V, Reed AM, Lundberg IE, Padyukov L
Arthritis Res Ther 2018 08;20(1):188

T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus.
Houtman M, Shchetynsky K, Chemin K, Hensvold AH, Ramsköld D, Tandre K, Eloranta ML, Rönnblom L, Uebe S, Catrina AI, Malmström V, Padyukov L
J Autoimmun 2018 06;90():28-38

Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis.
Rivera NV, Hagemann-Jensen M, Ferreira MAR, Kullberg S, Eklund A, Martin NG, Padyukov L, Grunewald J
Sci Rep 2017 07;7(1):5623

Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis.
Too CL, Murad S, Hansson M, Alm LM, Dhaliwal JS, Holmdahl R, Jakobsson PJ, Alfredsson L, Klareskog L, Rönnelid J, Padyukov L
Arthritis Rheumatol 2017 01;69(1):58-69

Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis.
Shchetynsky K, Protsyuk D, Ronninger M, Diaz-Gallo LM, Klareskog L, Padyukov L
Clin Immunol 2015 May;158(1):19-28

A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.
Bossini-Castillo L, de Kovel C, Kallberg H, van 't Slot R, Italiaander A, Coenen M, Tak PP, Posthumus MD, Wijmenga C, Huizinga T, van der Helm-van Mil AH, Stoeken-Rijsbergen G, Rodriguez-Rodriguez L, Balsa A, González-Álvaro I, González-Gay MÁ, Gómez-Vaquero C, Franke B, , Vermeulen S, van der Horst-Bruinsma Ie, Dijkmans BA, Wolbink GJ, Ophoff RA, Maehlen MT, van Riel P, Merriman M, Klareskog L, Lie BA, Merriman T, Crusius JB, Brouwer E, Martin J, de Vries N, Toes R, Padyukov L, Koeleman BP
Ann Rheum Dis 2015 Mar;74(3):e15

Genetic vectors as a tool in association studies: definitions and application for study of rheumatoid arthritis.
Sandalov I, Padyukov L
Int J Genomics 2015 ;2015():256818

Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Bridges SL, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapää-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M, , , Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K, Plenge RM
Nature 2014 Feb;506(7488):376-81

Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis.
Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, Shchetynsky K, Scheynius A, Kere J, Alfredsson L, Klareskog L, Ekström TJ, Feinberg AP
Nat Biotechnol 2013 Feb;31(2):142-7

The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls.
Ronninger M, Guo Y, Shchetynsky K, Hill A, Khademi M, Olsson T, Reddy PS, Seddighzadeh M, Clark JD, Lin LL, O'Toole M, Padyukov L
Genome Med 2012 Jan;4(1):2

TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.
Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR, Li W, Tan AK, Bonnard C, Ong RT, Thalamuthu A, Pettersson S, Liu C, Tian C, Chen WV, Carulli JP, Beckman EM, Altshuler D, Alfredsson L, Criswell LA, Amos CI, Seldin MF, Kastner DL, Klareskog L, Gregersen PK
N Engl J Med 2007 Sep;357(12):1199-209

Common variations in the IL4R gene affect splicing and influence natural expression of the soluble isoform.
Bergin AM, Balder B, Kishore S, Swärd K, Hahn-Zoric M, Löwhagen O, Hanson LA, Padyukov L
Hum Mutat 2006 Oct;27(10):990-8

A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis.
Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L
Arthritis Rheum 2004 Oct;50(10):3085-92