title: Altered expression of inflammatory cytokines in primary osteoarthritis by human T lymphotropic virus type I retrovirus infection: a cross-sectional study.
abstract: Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-terminal parathyroid hormone-related peptide (C-PTHrP), soluble interleukin-2 receptor (sIL-2R) and interleukin (IL)-6, and an osteo-destruction marker, deoxypyridinoline, in synovial fluid (SF) samples obtained from 22 HTLV-I carriers and 58 control non-carrier patients with OA. These patients were diagnosed clinically and radiographically with primary OA affecting one or both knee joints, and were similar with regard to age, sex and clinical symptoms. We also performed histopathological examination as well as immunohistochemistry of HTLV-I-derived Tax protein in eight synovial tissues taken from carrier patients. C-PTHrP in SF was significantly higher in HTLV-I carriers (287 +/- 280 pM) than in non-carriers (69 +/- 34 pM), and the concentration in 13 carriers was above the upper range of OA. In HTLV-I carriers, the concentrations of sIL-2R (741 +/- 530 IU/ml), IL-6 (55 +/- 86 ng/ml) and deoxypyridinoline (3.1 +/- 1.8 nM) were higher than in non-carriers (299 +/- 303, 2.5 +/- 4.0, 0.96 +/- 1.0, respectively), and correlated positively with C-PTHrP. C-PTHrP, sIL-2R and IL-6 concentrations in SF positive for IgM antibody against HTLV-I antigen, a marker of persistent viral replication, were higher than of IgM-negative SF. Histologically, five and two synovia showed mild and moderate synovial proliferation with or without some degree of inflammatory reaction, respectively, and could not be distinguished from OA. Tax-positive synoviocytes were observed sparsely in all samples, and often appeared frequently in actively proliferating regions. Our results suggest that although HTLV-I infection does not necessarily worsen the clinical outcome and local synovitis, the virus can potentially modify the pathophysiology of OA by increasing the inflammatory activity in a subset of carrier patients, especially those with IgM antibody. Longitudinal studies are required to assess the association between HTLV-I infection and OA.
authors.affiliation: Division of Orthopaedic Pathomechanism, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. yyoshihara-jsb@umin.ac.jp <yyoshihara-jsb@umin.ac.jp>
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yoshihara
authors.forename: Tomoo
authors.initials: T
authors.lastname: Tsukazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Osaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hasui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shindo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D024043:Collagen Type II; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016356:Gene Products, tax / Q000276:immunology / Q000378:metabolism; D015490:HTLV-I Infections / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000821:virology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D000596:Amino Acids; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D016207:Cytokines; D016356:Gene Products, tax; D015850:Interleukin-6; D044162:Parathyroid Hormone-Related Protein; D010455:Peptides; D015375:Receptors, Interleukin-2; C040072:chondrocalcin; C036020:deoxypyridinoline; D003094:Collagen