Polyspecificity of Monoclonal Lupus Autoantibodies Produced by Human-Human Hybridomas

125

Two common cross-reacting anti-DNA antibody idiotypes designated 1616 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.Evidence of a genetic basis for systemic lupus erythematosus (SLE) has been accumulated in a variety of studies. Population studies have indicated a particular predominance of black females (I), while [61). Recently, the frequency of the Gm allotype 1,17; 5,6,13 was shown to be significantly increased in black American SLE patients (7). Inherited complement deficiency states, notably those of the classical pathway and terminal sequence (C5-C9), have also been noted (8). In a recent study, more than 80% of white SLE patients were found to have a silent or null allele of C4A or C4B (and, in 1 patient, C2), compared with 40% of a matched normal control group (9). Finally, many asymptomatic relatives of lupus patients have hypergammaglobulinemia (lo), serum autoantibodies (1 I), raised circulating immune complex levels (12), and decreased suppressor T cell function (13).We now report a study of anti-DNA antibody idiotypes detectable in the serum of lupus patients and their first-degree relatives. The sharing of idiotypes by antibodies obtained from different patients would suggest that they are the products of germ-line genes that are dispersed throughout the population (14). There is clear evidence that the germ-line controls and limits the available and expressed idiotypic repertoire in newly arising B cells (15). The demonstration of shared idiotypes among lupus patients and their relatives would further support the concept of the importance of genetic influences in SLE.

Section: Discussionmentioning

confidence: 99%

Detection of cross‐reactive anti‐DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives

Isenberg¹,

Shoenfeld

Walport

et al. 1985

125

“…Three weeks later, a booster injection of I /Lg of SA-I in phosphate buffered saline (PBS) was administered to the hind footpads (8). The presence of autoantibodies against single-stranded DNA, dsDNA, poly(l), poly(G), histones (subfractions Hl-H5), cardiolipin, Sm, RNP, SS-A/Ro, SS-B/La, and 16/6 Id idiotype in the serum was determined by enzyme-linked immunosorbent assay (ELISA) (5,6,8,20,21). The mice were bled through their orbits, with 300 /Ll of serum obtained from each animal.…”

Section: Methodsmentioning

confidence: 99%

The effect of cyclosporin a on early and late stages of experimental lupus

Blank

Ben-Bassat

Shoenfeld

1992

Objective. To investigate the effect of cyclosporin A (CSA) on the development of lupus in an experimental model.Methods. Lupus was induced in naive mice following injection of a human anti-double-stranded DNA (anti-dsDNA) monoclonal antibody carrying the 16/6 idiotype (Id). CSA was injected into the mice at an early stage of the disease (2 months after immunization) and at a late stage (4 months after immunization).Results. CSA was found to have a suppressive effect on autoantibody production, as well as on the appearance of other disease manifestations, in the mice with lupus. The effects of the drug were more prominent when the mice were treated at an early stage. This was reflected by a dramatic decrease, to normal levels, in autoantibodies to dsDNA, histones, cardiolipin, Sm, RNP, SS-A/Ro, SS-B/La, and anti-DNA 16/6 Id. Similar effects on the erythrocyte sedimentation rate, white blood cell count, and urinary protein levels were noted.

“…The prevalence and the clinical importance of these antibodies have also been discussed in relation to the occurrence of human and mouse monoclonal antibodies against denatured DNA, and their cross-reactivity with cardiolipin and other phospholipids (4)(5)(6).…”

Section: Anticardiolipin Antibodies In Patients With Systemic Lupus Ementioning

confidence: 99%

Anticardiolipin antibodies in patients with systemic lupus erythematosus

Sturfelt

Nived

Norberg

et al. 1987

122

We studied a group of 59 unselected patients with systemic lupus erythematosus (SLE); these patients were from a defined population who lived in southern Sweden. We found that serum concentrations of anticardiolipin antibodies were increased in 32 SLE patients found. Serial serum samples from 28 patients (12 patients were from the epidemiologic cohort) were analyzed. Sixteen of these 28 patients (57.1%) had increased levels of anticardiolipin antibodies; in most cases, there was no variation in these values with regard to clinical disease Bares or treatment. Increased concentrations of anticardiolipin were observed in 4 patients with cerebral infarction. However, very high concentrations of anticardiolipin antibodies were observed in several patients with inactive SLE who had no history of thrombosis or thrombocytopenia. Our results underscore the importance of studying unselected patient groups when