Genetic factors predicting IFN-gamma generation potential in patients with sarcoidosis and after haematopoietic stem cell transplantation.
HLA B8, which is known to associate with a poor proliferative response, constitutes a risk factor of antinuclear antibodies formation in asbestos workers. B8 and DR3 are in a linkage disequilibrium with TNF*A2 allele which characterizes individuals as high TNF-alpha producers. Therefore, haplotype having B8, DR3, TNF*A2 characterizes individuals with rather low proliferative response of lymphocytes and low IFN-gamma generation potential. The above genetical features (B8, DR3 and TNF*A2), associated with a characteristic TNF alpha and IFN gamma generation profile, make sarcoidosis patients prone to develop Lofgren syndrome symptoms. Indeed, low IFN gamma producers genotype (3/3 homozygotes) and HLA DRB1*03 constitute risk factors of Lofgren syndrome in a combined fashion. In patients receiving hematopoietic stem cell transplantation, low IFN gamma producer genotype make people more susceptible to CMV and EBV reactivation as well as to acute and chronic GvHD. Therefore, genetical factors associated with the magnitude of immune response are of a value in predicting the natural history of some diseases thus helping in diagnosis and in tailoring of the treatment.
Lange
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Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. lange@iitd.pan.wroc.pl
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D012507:Sarcoidosis / Q000235:genetics* / Q000276:immunology; D014775:Virus Activation / Q000276:immunology
D016207:Cytokines; D007371:Interferon-gamma