CONCISE REPORT Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus

Objective—To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. Methods—In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. Results—Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/ respiratory renal, and haematological systems and with global BILAG score (p<0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. Conclusions—Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown. (Ann Rheum Dis 1998;57:566–570) Antibodies are usually defined by the antigens to which they bind. Another way of distinguishing antibodies serologically involves an analysis of their idiotypes that may be thought of as phenotypic markers of the variable region genes used to encode the antigen binding (Fab) region of immunoglobulin molecules. These regions encode tertiary structures termed idiotopes. A collection of these idiotopes may together be called an idiotype. Idiotypes may represent amino acid sequences located on light or heavy chains alone or in combination. The sharing of idiotypes by immunoglobulins from diVerent people implies that the genes that encode the idiotypes are also shared. In the past 12 years a number of idiotypes, recognised by polyclonal reagents and idiotopes, recognised by monoclonal antibodies, on DNA antibodies have been identified (reviewed by Isenberg et al). Among the 25 or so idiotypes or idiotopes, few can be regarded as specific for systemic lupus erythematosus (SLE) and a limited number have been correlated with disease activity. Among those that have shown correlation with disease activity and are present on immunoglobulins deposited in the renal lesions of tissue from patients are the 16/6, GN2 idiotypes and the 9G4 idiotope (Id). In our original report demonstrating the presence of the 9G4 Id in 45% of serum samples from patients with SLE, we showed that levels of this idiotope fluctuated with disease activity in some patients and the Id was detected in the kidney biopsy specimens of three of 11 patients. However, the global disease activity index (UCH/Middlesex) used in that study was not ideal, never having been tested for validity or reliability. In this study we have extended our earlier findings. By utilising a disease activity index shown to be validated and reproducible, we have attempted to determine whether 9G4 idiotope (Id) levels reflect that disease activity in a particular organ or system. We have also sought to determine whether the 9G4 Id in the serum samples of lupus patients is present on other antibodies with which it has been associated in other conditions such as anti-myeloperoxidase (MPO) antibodies and cold agglutinins, and have undertaken further absorption experiments. Methods PATIENTS Serum samples were drawn from 190 patients with SLE who met the revised criteria for the classification of the disease proposed by the American College of Rheumatologists. We Ann Rheum Dis 1998;57:566–570 566 Centre For Rheumatology/ Bloomsbury Rheumatology Unit, Department of Medicine University College London D A Isenberg C McClure W Williams G Cambridge Departments of Statistics, University College, London V Farewell Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, Southampton M Spellerberg F Stevenson Correspondence to: Professor D Isenberg, Bloomsbury Rheumatology Unit, Middlesex Hospital, Arthur Stanley House, 50 Tottenham Street, London W1P 9PG. Accepted for publication 20 July 1998 group.bmj.com on June 21, 2017 Published by http://ard.bmj.com/ Downloaded from