Autoantibody and idiotype profile of lung involvement in autoimmune rheumatic disease.

Several reports have linked the presence of certain serum autoantibodies with particular clinical manifestations of autoimmune disease. For example, the Jo-1 antibody is now established as a marker for fibrosing alveolitis in polymyositis. To investigate the possible association of further autoantibodies or idiotypes with fibrosing alveolitis in autoimmune rheumatic disease a panel of autoantibodies was measured in serum samples from 28 patients with systemic lupus erythematosus (SLE) (10 with and 18 without lung involvement), 21 patients with scleroderma (12 with fibrosing alveolitis and nine without), and 41 patients with 'lone' fibrosing alveolitis. Antibodies measured were IgM and IgG anti-dsDNA and anti-ssDNA antibody; IgG and IgM anticardiolipin antibody; anti-poly (ADP-ribose) antibody; antibodies to two common idiotypes of anti-DNA antibodies, designated 134 and 16/6; and IgM, IgG, and IgA isotypes of rheumatoid factor. None of these antibodies was specifically associated with lung involvement in SLE or scleroderma, but a trend was found towards an increase in all autoantibodies in association with lung disease in SLE, while the reverse trend was seen in scleroderma.

Disease specificity of antibodies to poly (ADP-ribose); their relationships to anti-DNA antibodies and to disease activity in lupus.

In this study we have measured the level of anti poly (ADP-ribose) antibodies in the sera of a number of patients with SLE and their relatives, patients with a wide variety of other autoimmune and infectious diseases, and a group of normal healthy controls. It was found that these antibodies were not disease specific but were present in nine out of thirteen groups tested in significant numbers. The levels of anti poly (ADP-ribose) antibodies and anti DNA antibodies in SLE patients bled serially were also measured. The level of these antibodies fluctuated in parallel in many of these patients, although the anti poly (ADP-ribose) antibodies reflected disease activity more accurately in some.

Disease activity in systemic lupus erythematosus related to a range of antibodies binding DNA and synthetic polynucleotides.

Antibodies to dDNA, nDNA, Z-DNA, poly(dT), poly(I), poly(dG.dC), poly(dA.dT), and total IgG and IgM were measured in five serial bleeds from 39 patients with systemic lupus erythematosus (SLE). The main findings were that those patients with renal disease form a distinct subset whose antibody levels correlate well with disease activity; anti-poly(dT) antibodies showed the best overall correlation with disease activity; and discriminant functional analysis demonstrated a major improvement in correlation of disease activity with combinations of antibodies to dDNA/nDNA/Z-DNA/poly(dT) (generally 50% or more were correctly classified) than with dDNA or nDNA alone (generally less than 25% correct). Serum IgG (but not IgM) correlated significantly (p less than 0.01) with six antibodies, suggesting that polyclonal activation plays a part in the development of these antibodies, though antibody cross reactivity is not excluded.

Measurement of anti-DNA antibodies: a reappraisal using five different methods.

One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). In most of the assays 3-9% of the controls were positive. When the SLE sera were analysed according to disease activity the IgG anti-dsDNA ELISA, all three RIA values, and the Crithidia test values were raised in all the patients with severely active disease. Some patients with inactive disease, however, were positive in each of the tests. The best interassay correlations (r less than 0.49) were found between RIA (UK), and ss IgG and the Amersham kit; and between ds IgG and ss IgG. In the main, however, it was clear that different assays are dependent upon distinctive properties of DNA antibodies. It seems inevitable that most major rheumatology units will require more than one anti-DNA antibody assay.

A study of antipolynucleotide antibodies, anti-Klebsiella (K30) antibodies and anti-DNA antibody idiotypes in ankylosing spondylitis.

Recent studies have indicated that both ankylosing spondylitis and the anti-DNA antibodies found in systemic lupus erythematosus may be related to Klebsiella surface antigens. In order to explore these possible relationships further, the sera of 24 patients with ankylosing spondylitis (AS), and 20 controls, have been examined for binding to a wide range of antipolynucleotide antibodies, antibodies binding to the Klebsiella pneumoniae polysaccharide K30 and two DNA antibody idiotypes designated 16/6 and 134. We report that although 21% of the AS patients had IgG ssDNA antibodies it is evident that the aetiopathogenesis of this disease is not through the mechanism of autoantibodies or the common DNA antibody idiotypes tested.

Profile of autoantibodies in the serum of patients with tuberculosis, klebsiella and other gram-negative infections.

Autoantibody profiles were examined in the sera of untreated patients with tuberculosis, and those with klebsiella septicaemia, and klebsiella and E. coli urinary tract infections. Rheumatoid factors of the IgM, IgA and IgG isotypes, antinuclear antibodies and antibodies to poly(ADP-ribose) were all frequently detected (generally 15-40%). In contrast, antibodies to the extractable nuclear antigens and to the organ specific antigens were unusual (generally less than 10%). In comparison, in a group of lupus patients IgM rheumatoid factor, anti-nuclear antibodies, antibodies to poly(ADP-ribose) and antibodies to the extractable nuclear antigens were more frequently found, but IgA and IgG rheumatoid factors and antibodies to the organ-specific antigens were present in much the same frequency.

A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members.

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE.

The relationship of anti-DNA antibody idiotypes and anti-cardiolipin antibodies to disease activity in systemic lupus erythematosus.

The detection of anti-cardiolipin antibodies and anti-DNA antibody idiotypes has shown utility in a prospective assessment of 42 lupus patients over a 1-year study period. However, so broad is the range of clinical and serological features included in the diagnostic category of SLE that even a combination of tests will often inadequately reflect disease activity at a given time. For the foreseeable future the value of laboratory investigations will probably lie in supporting clinical judgment of the nature of a patient's illness and the severity of the target organ's dysfunction.

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

Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 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.

Detection of cross reactive anti-DNA antibody idiotypes on tissue-bound immunoglobulins from skin biopsies of lupus patients.

Cross-reactive anti-DNA antibody idiotypes have been identified on tissue-bound immunoglobulins from skin biopsies of patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE). Four polyclonal and two monoclonal anti-idiotypic reagents were used to screen biopsies from 24 patients with SLE, 23 patients with DLE, and 15 other patients with IgM-positive skin biopsies. Up to 46% of the SLE patients and 30% of the DLE patients were found to share idiotypes present on immunoglobulins deposited at the dermal-epidermal junction. Inhibition studies in four patients indicated that the idiotypes were on anti-DNA antibodies. In contrast, none of the anti-idiotypic antibodies bound to any of the control biopsies. These findings imply that some tissue-bound autoantibodies are derived from related families of high-frequency germ-line genes that are expressed in both SLE and DLE.