title: Exposure of HEp-2 cells to stress conditions influences antinuclear antibody reactivity.
abstract: This study of stress-related antinuclear antibody (ANA) reactivity was undertaken with the objective of improving clinical ANA testing. ANA was determined by parallel enzyme-linked immunosorbent assays of crude nuclear protein antigen extracted from HEp-2 cells either grown under optimal conditions (providing nonstress ANA antigen) or exposed to stress (providing stress ANA antigen). The stress stimuli used were gamma radiation (causing DNA damage) and a hypertonic environment (causing apoptosis). Signs of stress-related ANA reactivity were seen among connective tissue disease (CTD) patients (including patients with systemic lupus erythematosus; mixed CTD; calcinosis, Reynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia; scleroderma; and Sjögren's syndrome): 11% showed stress-positive ANA (i.e., a significantly stronger ANA reactivity with the extract from stressed cells), whereas 21% showed a markedly weaker reaction with the stress antigen. In contrast, among ANA screening patient sera, with no diagnosis of CTD, the fraction showing stress-positive ANA was higher (7 to 8%, depending on the type of stress) than among those showing a lower reactivity with stress antigen (1.5 to 2.5%). Only one serum among 89 (1%) tested sera from healthy individuals showed a stress-related ANA reaction. This demonstration of stress-related ANA suggests a means to improve the performance of clinical ANA testing.
authors.affiliation: Department of Medical Microbiology, Lund University, Malmo University Hospital, S-205 02 Malmo, Sweden.
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.forename: Sachiko
authors.initials: S
authors.lastname: Fukushima
authors.forename: Annahita
authors.initials: A
authors.lastname: Sallmyr
authors.forename: Rolf
authors.initials: R
authors.lastname: Manthorpe
authors.forename: Anders
authors.initials: A
authors.lastname: Bredberg
mesh_terms: D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology; D004249:DNA Damage; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D006982:Hypertonic Solutions; D009997:Osmotic Pressure; D014407:Tumor Cells, Cultured
chemical_list: D000974:Antibodies, Antinuclear; D000939:Epitopes; D006982:Hypertonic Solutions