title: HLA-G may predict the disease course in patients with early rheumatoid arthritis.
abstract: The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients.
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy. rbr@unife.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Farina
authors.forename: Daria
authors.initials: D
authors.lastname: Bortolotti
authors.forename: Elisa
authors.initials: E
authors.lastname: Galuppi
authors.forename: Antonella
authors.initials: A
authors.lastname: Rotola
authors.forename: Loredana
authors.initials: L
authors.lastname: Melchiorri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciancio
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
authors.forename: Marcello
authors.initials: M
authors.lastname: Govoni
mesh_terms: D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004252:DNA Mutational Analysis; D042241:Early Diagnosis; D005091:Exons; D005260:Female; D015870:Gene Expression; D059951:HLA-G Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D020033:Protein Isoforms / Q000097:blood / Q000276:immunology; D011971:Receptors, Immunologic / Q000097:blood / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D059951:HLA-G Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D020033:Protein Isoforms; D011971:Receptors, Immunologic