title: Genetically determined imbalance between serum levels of tumour necrosis factor (TNF) and interleukin (IL)-10 is associated with anti-Jo-1 and anti-Ro52 autoantibodies in patients with poly- and dermatomyositis.
abstract: Our aim was to investigate presence of tumour necrosis factor (TNF) and interleukin (IL)-10 in serum and their relation to different genotypes as well as to clinical and laboratory phenotypes in patients with polymyositis and dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory cytokine balance was evaluated by the assessing absolute levels as well as the ratio between TNF and IL-10 in serum. These levels were correlated to the G-308A TNFA, G-1087A IL10 and G915C TGFB1 gene polymorphisms and haplotype frequencies, gender, autoantibody profiles and clinical manifestations. Increased serum levels of TNF and IL-10 were observed in patients compared to controls. A significantly higher TNF:IL-10 ratio was detected in female poly- and dermatomyositis patients carrying the TNF2 allele compared to female patients with the TNF1/TNF1 genotype (median+/-IQR 1.513+/-0.0.679 vs. 0.950+/-1.173, p=0.021). This ratio was also significantly higher in patients with the extended MICA5.1/TNF2/TNFa2/DRB1*03 haplotype compared to patients lacking this haplotype. A significantly higher TNF:IL-10 ratio was recorded in sera of patients with anti-Ro52 (1.513+/-1.275 and 1.276+/-0.671, positive vs. negative, p=0.010) antibodies and in women with anti-Jo-1 (1.919+/-0.918 and 1.281+/-0.790, positive vs. negative, p=0.041). Our data suggest that a genetically programmed cytokine imbalance exists in patients with poly- or dermatomyositis and that this imbalance is related to the presence of disease-associated autoantibodies.
authors.affiliation: Department of Medicine, Rheumatology Unit, CMM L8:O4, Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Adla B
authors.initials: AB
authors.lastname: Hassan
authors.forename: Maryam
authors.initials: M
authors.lastname: Fathi
authors.forename: Maryam
authors.initials: M
authors.lastname: Dastmalchi
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003882:Dermatomyositis / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006643:Histidine-tRNA Ligase / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012261:Ribonucleoproteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D006643:Histidine-tRNA Ligase; D016753:Interleukin-10; D012261:Ribonucleoproteins; D014409:Tumor Necrosis Factor-alpha; D000099207:SS-A Antigen