PMID- 25791751
OWN - NLM
STAT- MEDLINE
DCOM- 20160401
LR  - 20181113
IS  - 1559-0267 (Electronic)
IS  - 1080-0549 (Linking)
VI  - 49
IP  - 1
DP  - 2015 Aug
TI  - Immunogenetics of Disease-Causing Inflammation in Sarcoidosis.
PG  - 19-35
LID - 10.1007/s12016-015-8477-8 [doi]
AB  - Sarcoidosis is a systemic inflammatory disorder characterised by tissue 
      infiltration by mononuclear phagocytes and lymphocytes with associated 
      non-caseating granuloma formation. Originally described as a disorder of the 
      skin, sarcoidosis can involve any organ with wide-ranging clinical manifestations 
      and disease course. Recent studies have provided new insights into the mechanisms 
      involved in disease pathobiology, and we now know that sarcoidosis has a clear 
      genetic basis largely involving human leukocyte antigen (HLA) genes. In contrast 
      to Mendelian-monogenic disorders--which are generally due to specific and 
      relatively rare mutations often leading to a single amino acid change in an 
      encoded protein--sarcoidosis results from genetic variations relatively common in 
      the general population and involving multiple genes, each contributing an effect 
      of varying magnitude. However, an individual may have the necessary genetic 
      profile and yet the disease will not develop unless an environmental or 
      infectious factor is encountered. Genetics appears also to contribute to the huge 
      variability in clinical phenotype and disease behaviour. Moreover, it has been 
      established that sarcoidosis granulomatous inflammation is a highly polarized T 
      helper 1 immune response that starts with an antigenic stimulus followed by T 
      cell activation via a classic HLA class II-mediated pathway. A complex network of 
      lymphocytes, macrophages, and cytokines is pivotal in the orchestration and 
      evolution of the granulomatous process. Despite these advances, the aetiology of 
      sarcoidosis remains elusive and its pathogenesis incompletely understood. As 
      such, there is an urgent need for a better understanding of disease pathogenesis, 
      which hopefully will translate into the development of truly effective therapies.
FAU - Grunewald, Johan
AU  - Grunewald J
AD  - Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska 
      Institutet and Karolinska University Hospital, Solna, Sweden.
FAU - Spagnolo, Paolo
AU  - Spagnolo P
FAU - Wahlstrom, Jan
AU  - Wahlstrom J
FAU - Eklund, Anders
AU  - Eklund A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Rev Allergy Immunol
JT  - Clinical reviews in allergy & immunology
JID - 9504368
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Cytokines/genetics/immunology
MH  - Erythema Nodosum/genetics/immunology/pathology
MH  - Gene Expression Regulation
MH  - Granuloma/genetics/immunology/*pathology
MH  - Histocompatibility Antigens Class II/genetics/*immunology
MH  - Humans
MH  - Inflammation
MH  - Lymphatic Diseases/genetics/immunology/pathology
MH  - Macrophages/immunology/*pathology
MH  - Mycobacterium tuberculosis/immunology/pathogenicity
MH  - Phenotype
MH  - Propionibacterium acnes/immunology/pathogenicity
MH  - Receptors, Chemokine/genetics/immunology
MH  - Sarcoidosis/genetics/immunology/*pathology
MH  - Signal Transduction
MH  - Th1 Cells/immunology/*pathology
EDAT- 2015/03/21 06:00
MHDA- 2016/04/02 06:00
CRDT- 2015/03/21 06:00
PHST- 2015/03/21 06:00 [entrez]
PHST- 2015/03/21 06:00 [pubmed]
PHST- 2016/04/02 06:00 [medline]
AID - 10.1007/s12016-015-8477-8 [doi]
PST - ppublish
SO  - Clin Rev Allergy Immunol. 2015 Aug;49(1):19-35. doi: 10.1007/s12016-015-8477-8.