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Identification and Characterization of a New Human DNA Reactive Monoclonal Antibody and a Common Idiotype, WRI 176 Id ß

Bloomsbury Rheumatology Unit/The Department of Medicine, University College London Medical School, London, UK

C. Longhurst

Division of Molecular Pathology, University College London Medical School, London, UK

R. Watts

Department of Rheumatology, Addenbrookes Hospital, Cambridge, UK

J. Kalsi

Bloomsbury Rheumatology Unit/The Department of Medicine, University College London Medical School, London, UK

H. Winska Wiloch

Bloomsbury Rheumatology Unit/The Department of Medicine, University College London Medical School, London, UK

P. Youinou

Immunology Laboratory, University of Brest, France

D.S. Latchman

Division of Molecular Pathology, University College London Medical School, London, UK

D.A. Isenberg

Bloomsbury Rheumatology Unit/The Department of Medicine, University College London Medical School, London, UK

We describe a human monoclonal antibody designated WRI 176 ß and a common idiotype that it carries. This antibody was derived from the spleen of a patient with SLE. WRI 176 is an IgM kappa monoclonal reacting with ssDNA, dsDNA, poly(dT) and it is likely that mAb WRI 176 ß is a representative of the so-called natural autoantibodies. The common Id designated WRI 176 Id ß is located on the heavy chain of the mAb WRI 176 ß molecule and appears to be located outside the binding site. Sequence analysis of the WRI 176 ß heavy chain showed it to be highly homologous (97.3%) with a germline gene 56PI derived from a human fetus. In a retrospective analysis, although 44% of SLE patients had raised levels of the WRI 176 ß no correlation was found with the activity of the disease. The idiotype was also expressed frequently in a range of autoimmune rheumatic and infectious diseases and in some healthy first-degree relatives of SLE patients.

Key Words: Antibody • Idiotype • Anti-DNA • SLE • Antibody gene

Lupus, Vol. 3, No. 1, 15-24 (1994)
DOI: 10.1177/096120339400300105


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