Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: ...

@article{2294404,
   author = {Sikorova, K. and Osoegawa, K. and Kocourkova, L. and Strnad, A. and Petrkova, J. and FernandezandVina, M. A. and Doubková, Martina and Petrek, M.},
   article_location = {Laussane},
   article_number = {April 2023},
   doi = {http://dx.doi.org/10.3389/fmed.2023.1094843},
   keywords = {sarcoidosis; HLA; Czech; clinical course; Lofgren's syndrome; biomarker; inflammatory disorders},
   language = {eng},
   issn = {2296-858X},
   journal = {Frontiers in Medicine},
   title = {Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment},
   url = {https://www.frontiersin.org/articles/10.3389/fmed.2023.1094843/full},
   volume = {10},
   year = {2023}
}

TY  - JOUR
ID  - 2294404
AU  - Sikorova, K. - Osoegawa, K. - Kocourkova, L. - Strnad, A. - Petrkova, J. - Fernandez-Vina, M. A. - Doubková, Martina - Petrek, M.
PY  - 2023
TI  - Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment
JF  - Frontiers in Medicine
VL  - 10
IS  - April 2023
SP  - 1-11
EP  - 1-11
PB  - Frontiers
SN  - 2296858X
KW  - sarcoidosis
KW  - HLA
KW  - Czech
KW  - clinical course
KW  - Lofgren's syndrome
KW  - biomarker
KW  - inflammatory disorders
UR  - https://www.frontiersin.org/articles/10.3389/fmed.2023.1094843/full
N2  - BackgroundSarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Lofgren's syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors' role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development. Materials and methodsTotal of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. ResultsWe report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Lofgren's syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis-chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2-4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation. ConclusionIn our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01 similar to HLA-B*08:01 similar to HLA-C*07:01 similar to HLA-DRB1*03:01 similar to HLA-DQA1*05:01 similar to HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.
ER  - 

SIKOROVA, K., K. OSOEGAWA, L. KOCOURKOVA, A. STRNAD, J. PETRKOVA, M. A. FERNANDEZ-VINA, Martina DOUBKOVÁ and M. PETREK. Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment. \textit{Frontiers in Medicine}. Laussane: Frontiers, 2023, vol.~10, April 2023, p.~1-11. ISSN~2296-858X. Available from: https://dx.doi.org/10.3389/fmed.2023.1094843.