MESARGEN – Multi-Ethnic Sarcoidosis Genomics Consortium


Our goal in this international initiative is to provide the opportunity to tackle various research aspects in the genomics of sarcoidosis with scientific rigor and clinical relevance. Therefore, the MESARGEN consortium was created.

MESARGEN is an international framework created by Natalia Rivera (Principal Investigator) in the Respiratory Medicine Division chaired by Johan Grunewald at the Department of Medicine Solna, Karolinska Institutet.

The purpose of MESARGEN is to be able to conduct genomic investigations using large sample sizes including diverse ethnic populations with well-phenotyped clinical data and molecular phenotypes. Along with various omics technologies coupled with cutting-edge bioinformatics and statistical methods, we intend to elucidate disease mechanisms underlying sarcoidosis pathogenesis and identify biomarkers that can be used for diagnosing or predicting disease outcomes. The discovery of molecular targets could potentially lead to more realistic gene-based therapies.

At present, the MESARGEN consortium has brought together many scientific and clinical investigators from across the globe. Current participating cohorts from different countries include Sweden (coordinating center), Finland, Denmark, Germany, Greece, Spain, Portugal, the Netherlands, the Czech Republic, Italy, Ukraine, Moldova, Latvia, Poland, Serbia, Belgium,  the United States, South Korean, Japan, and India. MESARGEN also includes data from established biobanks, including the United Kingdom biobank (UK-Biobank) and Finnish biobank (FinnGen).



Impact of sarcoidosis

Several features in sarcoidosis phenotypes, Lofgren’s syndrome (LS) and non-Lofgren’s syndrome (non-LS), such as the variability in the clinical presentation and the lack of case definitions of disease – pose a challenge for epidemiological studies to deduce underlying causes of disease and etiology since these features are ascertainment bias. A further difficulty arises when a high proportion of patients with either sarcoidosis phenotype (LS or non-LS) are asymptomatic and the finding of the disease is by chance. Taken together, these difficulties result in a degree of disease misclassifications leaving the patient undiagnosed for the disease.

Epidemiological evidence indicates that sarcoidosis and its main phenotypes, LS and non-LS, have low prevalence across the world, and in some populations these are considered rare phenotypes. Pooled LS and non-LS cases together under the classification of sarcoidosis, the disease prevalence ranges from 0.2 per 100,000 in South America to 64 per 100,000 in Sweden. Sarcoidosis is roughly as common in men as in women and has the tendency to present in young adulthood (rarely in childhood). Race and ethnicity are strong factors that markedly influence disease presentation, prevalence, and incidence.
Sarcoidosis (either LS or non-LS) affects the life-style of young individuals who are referred to specialized respiratory clinics, generating significant direct and indirect healthcare cost.

In many patients, sarcoidosis, specifically the LS phenotype regresses on its own over a period of 2-5 years whilst in the majority of the patients, mainly those diagnosed with  non-LS, the disease progresses over the years, sometimes involving more than two organs e.g., lungs, heart, kidney, eyes, skin, nervous system, musculoskeletal system, reproductive system, lymph nodes, live, and spleen – which  are progressively infiltrated and compromised with extensive fibrosis.

Death from sarcoidosis, particularly in patients affected by the non-LS phenotype, is about five percent. Deaths are commonly attributed either to progressive lung scarring  such as fibrosis, complicated by bleeding from the lung vessels, i.e., respiratory failure or to development of granulomas in the lungs and/or in the heart causing abnormal heart rhythms and thereby resulting in failure of the heart’s right ventricle.

Genetic determinants in sarcoidosis

Evidence points out that phenotypes of sarcoidosis, that is, LS and non-LS, are disease entities enhanced by T-cell mediated immune responses at sites of granulomatous inflammation; however, specific determinants underlying molecular mechanisms and regulation in disease pathology have not yet been identified. In fact, sarcoidosis  phenotypes LS and non-LS are multifactorial disease entities likely to result from the interplay between multiple genes and perhaps also environmental factors – each exerting only a modest effect on the overall risk. The distinctive genetic arrangements in each phenotype poise important functions that contribute to the disease diversity observed in the clinical presentation and course of the disease.

Sarcoidosis and autoimmunity

The pathologic hallmark in sarcoidosis phenotypes, LS and non-LS, is characterized by granulomatous tissue comprised by epithelioid cells, CD4 lymphocytes, mature macrophages, multinucleated giant cells, CD8 lymphocytes, antigen-presenting cells (APCs), and cellular mechanisms orchestrated by assemblies of inflammatory machineries. Moreover, research evidence suggests that in both phenotypes an adaptive-mediated immune response mechanism drives the genetic architecture of each  phenotype.Whether this mechanism is the same in both is an active research field.


Currently, MESARGEN includes cohorts and molecular data from different ethnic populations


Sweden: Karolinska Institutet, Stockholm; Karolinska University Hospital

Principal investigators: Natalia Rivera; Johan Grunewald; Susanna Kullberg; Anders Eklund

Czech Republic: Palacky University Olomouc, Olomouc

Principal investigator: Martin Petrek

Poland: Medical University of Gdansk, Gdansk

Principal investigator: Anna Dubaniewicz

The Netherlands: University Medical Center Utrecht, Utrecht; St. Antonius Hospital, Nieuwegein

Principal investigators: Coline van Moorsel; Jan Grutters

Germany: TBA

Portugal: TBA

Spain: Hospital Universitario De Bellvitge, Barcelona; Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada

Principal investigators: Joan Mana Rey; Javier Martin

Italy: Universita di Siena; Policlinico Santa Maria alle Scotte, Siena;

Principal investigators: Paola Rottoli; David Bennet

Greece: Attikon University Hospital, Athens; National and Kapodistrian University of Athens, Athens; Hospital of Diseases of the Chest Sotiria Athens; Laboratory of Biology Medical School National and Kapodistrian Univ of Athens

Principal investigators:  Spyros Papiris; Efrosyni Manali;  Demosthenes Bouros; Maria Gazouli





The United States: TBA


MESARGEN strives at translating research discoveries in sarcoidosis emerging from large-scale omics studies in molecular epidemiology to future advances in clinical and personalized medicine.

The overall objectives of MESARGEN are to:

  • Establish an international framework for research into omics studies
  • Investigate risk factors and causes of sarcoidosis and subphenotypes
  • Provide a research platform for sharing and integration of large data sets
  • Explore key methodological questions to sarcoidosis and other pulmonary immune-related diseases
  • Facilitate translation of research discoveries to the clinic


Genetic investigations of sarcoidosis sub-phenotypes: Lofgren syndrome (LS) and Non-Lofgren syndrome (non-LS) – revealed that these sub-phenotypes have their own genetic architecture with a common genomic overlap located on the extended major histocompatibility complex (MHC) region.


Lofgren syndrome (LS), non-Lofgren syndrome (non-LS), and healthy controls (HC)

Further details available in High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.

Rivera NV, Ronninger M, Shchetynsky K, Franke A, Nöthen MM, Müller-Quernheim J, Schreiber S, Adrianto I, Karakaya B, van Moorsel CH, Navratilova Z, Kolek V, Rybicki BA, Iannuzzi MC, Petrek M, Grutters JC, Montgomery C, Fischer A, Eklund A, Padyukov L, Grunewald J.  Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC. PMID:26651848


Our latest work (as of July 2017):



“Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis” in Scientific Reports is available by using the following link:


Our goal on this initiative is to provide the opportunity to tackle various research aspects in sarcoidosis.

A summary slide of our initiative is given below …