title: X-linked immunodeficient mice spontaneously produce lupus-related anti-RNA helicase A autoantibodies, but are resistant to pristane-induced lupus.
abstract: Murine lupus can occur spontaneously or be induced by hydrocarbons, such as pristane. Spontaneous disease in MRL and NZB/W F1 mice is suppressed by the xid (X-linked immunodeficiency) mutation, which greatly diminishes T cell-independent type 2 responses as well as the number of peritoneal B1 cells. The present study asked whether lupus induced by i.p. injection of pristane likewise is inhibited by the xid defect. Male CBA/N (xid) mice were refractory to the induction of autoantibodies by pristane, whereas 23% of pristane-treated male CBA/CaJ controls produced anti-nRNP/Sm, -Su and/or -OJ (isoleucyl tRNA synthetase) antibodies. Unexpectedly, 43% (12 of 28) of the xid mice spontaneously produced anti-nuclear antibodies that proved highly specific for the lupus antigen RNA helicase A (RHA). Strikingly, this specificity was absent in CBA/CaJ mice (none of 51). Moreover, pristane treatment suppressed the production of anti-RHA antibodies when administered prior to the onset of autoantibody production, but enhanced anti-RHA levels when given after the onset of autoantibody production, suggesting that pristane interferes with anti-RHA production at an early stage. Large amounts of IgG1 anti-RHA autoantibodies were detected in the sera of xid mice, whereas pristane-induced anti-nRNP/Sm and -Su autoantibodies were almost exclusively IgG2a. Cytokine production within the peritoneal cavity reflected the predominant isotypes: IL-12 and IFN-gamma predominated in pristane-treated mice, whereas IL-4 and IL-6 were more predominant in untreated xid mice. The spontaneous production of anti-RHA by xid mice and its suppression by pristane treatment at the level of autoantibody induction supports the idea that lupus autoantibodies may be generated through a variety of mechanisms.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA. satohm@medicine.ufl.edu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Akiei
authors.initials: A
authors.lastname: Mizutani
authors.forename: Krista M
authors.initials: KM
authors.lastname: Behney
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Michito
authors.initials: M
authors.lastname: Hirakata
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ono
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D053487:DEAD-box RNA Helicases; D004277:DNA, Single-Stranded / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009363:Neoplasm Proteins; D020365:RNA Helicases / Q000276:immunology*; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D013729:Terpenes; C009042:pristane; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases