title: Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice.
abstract: Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti-Ro [Sjögren's syndrome antigen A (SSA)] and anti-La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti-Ro and anti-La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro-peptide immunization produces a Sjögren's-like illness in other strains of mice. BALB/c, DBA-2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide-274. Sera from these mice were studied by immunoblot and enzyme-linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA-2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's-like illness after Ro-peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction.
authors.affiliation: Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Kurien
authors.forename: A
authors.initials: A
authors.lastname: Dsouza
authors.forename: A
authors.initials: A
authors.lastname: Igoe
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: J S
authors.initials: JS
authors.lastname: Maier-Moore
authors.forename: T
authors.initials: T
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Jackson
authors.forename: R H
authors.initials: RH
authors.lastname: Scofield
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002217:Carbachol / Q000494:pharmacology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005620:Freund's Adjuvant; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D007114:Immunization; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D062706:Prodromal Symptoms; D020733:RNA, Small Cytoplasmic / Q000276:immunology*; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology*; D012469:Salivary Glands / Q000473:pathology; D012472:Salivation; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D001743:Urinary Bladder; D014987:Xerostomia / Q000209:etiology / Q000276:immunology; D000097585:SS-B Antigen
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D002217:Carbachol; D000939:Epitopes; D005620:Freund's Adjuvant; D006183:H-2 Antigens; D010446:Peptide Fragments; D020733:RNA, Small Cytoplasmic; D043587:Receptor, Muscarinic M3; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C035356:SS-A antibodies; C492050:Ssa2 protein, mouse