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Clinical and Diagnostic Laboratory Immunology, March 2002, p. 287-294, Vol. 9, No. 2
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.2.287-294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity

Liping Du,1 Sachiko Fukushima,1 Annahita Sallmyr,1 Rolf Manthorpe,2 and Anders Bredberg1*

Department of Medical Microbiology,1 Sjögren's Syndrome Research Centre, Department of Rheumatology, Lund University, Malmo University Hospital, S-205 02 Malmo, Sweden2

Received 5 July 2001/ Returned for modification 30 September 2001/ Accepted 1 November 2001

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.


* Corresponding author. Mailing address: Department of Medical Microbiology, Malmo University Hospital, S-205 02 Malmo, Sweden. Phone: 46-40-337414. Fax: 46-40-336234. E-mail: anders.bredberg{at}mikrobiol.mas.lu.se.


Clinical and Diagnostic Laboratory Immunology, March 2002, p. 287-294, Vol. 9, No. 2
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.2.287-294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.