Biomedical subjects
Publications and source records attributed to F Tron.
A monoclonal antibody directed against double stranded DNA obtained by fusion between myeloma cells and spleen cells from auto-immune B/W Mice, binds to protein(s) at the plasma membrane of human B lymphoblastoid cell lines Raji.
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Plasma androgen levels were determined by radio-immunoassay in 19 female patients (aged 14 to 42 years) with systemic lupus erythematosus (SLE). In 11 patients studied in the active phase of the disease, prior to any corticosteroid therapy, mean (+/- SEM) plasma concentrations (ng/ml) of the following androgens were significantly reduced as compared with controls (12 normal women aged 19-37 years): testosterone (0.119 +/- 0.021 vs 0.330 +/- 0.034, p less than 0.001), dihydrotestosterone (0.078 +/- 0.013 vs 0.150 +/- 0.014, p less than 0.01), dehydroepiandrosterone (1.60 +/- 0.16 vs 4.30 +/- 0.50, p less than 0.001), dehydroepiandrosterone sulfate (480 +/- 102 vs 1020 +/- 92, p less than 0.001), and androstenedione (0.69 +/- 0.22 vs 1.45 +/- 0.18, p less than 0.02). In 8 patients studied while in post-therapeutic remission, six months to seven years after corticosteroid withdrawal, plasma concentrations of the same androgens (except androstenedione) were also significantly reduced as compared with controls, although to a lesser degree. In neither of the two patient groups were cortisol and estradiol levels significantly different from controls. Our results suggest that low plasma androgen levels could be a permanent disorder in female SLE patients, at least in severe forms of the disease.
The influence of lupus nephropathy on pregnancy and reciprocally was retrospectively studied in a series of 131 pregnancies observed from 1962 to 1981 in 45 systemic lupus erythematosis (SLE) women with renal involvement. Renal biopsy showed proliferative lupus glomerulonephritis in 27. The incidence of live births, corrected for induced abortions, was 87% in 89 pregnancies started before, and 89% in 32 started after the clinical onset of SLE; it was only 63% in 10 cases where lupus nephritis developed during gestation. Relapse or exacerbation of disease activity occurred in 15 (47%) of 32 pregnancies antedated by the onset of SLE, with irreversible renal failure in two cases. Clinical exacerbation of SLE was observed in 13 (76%) of 17 cases where SLE was clinically active at the time of conception, and in only 2 of 15 cases where lupus nephritis was in stable clinical remission for at least 5 months prior to conception. Our data suggest that a successful outcome of pregnancy, without SLE exacerbation, may be expected, even in the more severe forms of lupus nephritis, when gestation begins after a sustained, complete clinical remission.
The clonal heterogeneity of nine monoclonal antibodies with absolute specificities for deoxyribonucleic acid (DNA) was analyzed. These monoclonal anti-DNA antibodies were generated in three different fusion experiments using autoimmune (NZB X NZW)F1 mouse spleen cells. Isoelectric focusing analyses demonstrated different isoelectric points within the IgG2a and IgG2b subclasses. Three anti-idiotypic antisera were prepared (one in a rabbit and two in mice) against two monoclonal anti-DNA antibodies. These antisera detected idiotypic determinants uniquely associated with homologous hybridoma anti-DNA antibodies. Two of these idiotypes could be detected at low levels in the sera of (NZB X NZW)F1 mice. Anti-PME77 idiotypic antiserum had no effect in vitro on the total binding capacity of (NZB X NZW)F1 sera. Taken together these results demonstrate that, in (NZB X NZW)F1 mice, the anti-DNA antibody repertoire contains molecules that show similar antigen binding characteristics but are not structurally uniform.
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Influence of oral contraceptive therapy on SLE activity was evaluated in 33 female patients with lupus nephropathy. Estroprogestative preparations containing either 50 micrograms (18 cases) or 30 micrograms (11 cases) of ethinylestradiol were used in 29 courses in 28 patients. Onset or exacerbation of clinical SLE activity occurred within 3 months after starting hormonal therapy in 13 cases, an overall incidence of lupus flare-up of 44 percent, involving major renal histological lesions in 5 cases. In contrast, of 16 patients receiving pure progestogen contraceptive therapy with either discontinuous normal dosage progestogens (9 cases) or continuous low-dose norsteroids (7 cases), only one developed clinical or immunological evidence of lupus exacerbation within 3 months of hormonal therapy. We conclude that oral contraceptive therapy using estrogens, even at low dosage, is associated with a high risk of SLE exacerbation. Pure progestogens, which have proven effective and devoid of such unfavorable effects, should be preferred in these patients when hormonal contraception is needed.
The reciprocal influence of lupus nephropathy on the outcome of pregnancy and of pregnancy on the course of renal involvement was studied retrospectively in a series of 106 pregnancies observed during the past two decades in 36 patients with lupus nephropathy. The overall incidence of live births, corrected for induced abortions, was 54 (84%) in 64 pregnancies that began before clinical onset of systemic lupus erythematosus (SLE), 20 (87%) in 23 pregnancies that began after onset of SLE, and only four (57%) in seven cases where SLE was first manifested during or after gestation. Relapse or exacerbation of disease activity occurred in 12 (46%) of 26 pregnancies antedated by clinical onset of SLE, more frequently during gestation than post partum, with two cases (8%) of irreversible deterioration of renal function; clinical exacerbation of lupus disease was observed in 11 (66%) of 15 cases where SLE was clinically active at the time of conception, and in only one (9%) of 11 cases where SLE nephritis was in stable clinical remission for at least five months before conception. The data indicate that successful outcome of pregnancy may be expected even in the more severe forms of lupus nephritis if gestation begins after a sustained, complete clinical remission.
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Since harmful effects of estrogens in murine lupus are well established, we studied the influence of oral contraceptive therapy on systemic lupus erythematosus activity in 26 female patients with lupus nephropathy. Combined preparations containing either 50 micrograms (14 patients) or 30 micrograms (7 patients) of ethinyl-estradiol were used in 21 courses in 20 patients. Initial manifestations or exacerbations of systemic lupus activity appeared within 3 months of beginning hormonal therapy in 9 patients, an overall incidence of lupus flare-up of 43%; there was major renal involvement in 4 patients. Conversely, evidence of lupus exacerbation did not develop in any of 11 patients who received pure progestogen oral contraceptive therapy with either continuous low-dose norsteroids (6 patients) or discontinuous progestogens at normal dosage (5 patients). These patients were followed for 5--30 months. Our data indicated that oral contraceptive therapy that used estrogens, even at low doses, often induced exacerbation of systemic lupus erythematosus activity. Pure progestogens, which were effective and devoid of such unfavorable effects, may be preferred in these patients.
Immunization of NZB and A/J mice against an anti-DNA hybridoma antibody (F227) derived from (NZB x NZW)F1 (B/W) mice allowed the preparation of two anti-idiotypic antisera. These two reagents were shown to recognize different idiotopes of the F227 monoclonal antibody. NZB anti-idiotypic antibodies recognized non-ligand-modifiable idiotypic determinants. These idiotopes were private or present at undetectable level in BW mouse sera since it was found that only two of the 24 B/W mouse sera tested were recognized by these antibodies. Conversely, A/J anti-idiotypic antibodies recognized partially ligand-modifiable idiotopes which were found in all B/W mouse sera tested. These results demonstrate that anti-DNA antibodies share similar idiotypic specificities and suggest that these autoantibodies occur as families of structurally related proteins.
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Ten monoclonal anti-DNA antibodies generated in three separate fusion experiments performed using nonimmunized B/W spleen cells were studied. Their antigenic specificities were demonstrated to be identical and directed against a conformational determinant of the B helical form of double-stranded DNA (dsDNA). These data suggest that autoantibodies to dsDNA in B/W mice could constitute a homogeneous population.
The presence of DNA-anti-DNA immune complexes in sera from patients with systemic lupus erythematosus (SLE) was investigated by a new solid phase radioimmunoassay (RIA). This assay used murine monoclonal anti-double stranded DNA (dsDNA) antibody to recognize DNA present in the complexes and 125I-rabbit anti-human gamma globulin as a tracer. DNA-anti-DNA immune complexes were found in certain SLE sera but not in sera from patients with other immune complex diseases and from healthy blood donors. The presence of circulating DNA-anti-DNA complexes was associated with low C4 levels. It was not related to the presence of immune complexes detected by the polyethylene glycol assay suggesting either that the assay did not detect all DNA-anti-DNA complexes or that other antigen-antibody systems constitute the major immune complex components in SLE sera. The clinical significance of circulating DNA-anti-DNA complexes in SLE sera as well as the potential use of this solid phase RIA using various monoclonal antibodies to detect specific antigen-antibody systems is discussed.
We report a case of Takayasu's disease in a young Algerian woman with severe renovascular hypertension that failed to respond to medical treatment. There was a general inflammatory syndrome but no important immunological abnormality. Histology showed non-specific aortoarteritis. A left nephrectomy was done, a monofilament knitted polypropylene prosthesis was placed between the thoracic aorta and the aortic bifurcation, and an aorto-reno-mesenteric graft was inserted. The patient was normotensive with no further therapy 2 years later.
Sixty-five patients with systemic lupus erythematosus were followed up for periods of 8 to 48 months. Sixty-six clinical exacerbations of the disease were observed and treated with various, non-randomized therapeutic regimens. The relationship between the results of immunological tests (DNA binding rate, serum levels of C3 and C4, presence of immune complexes and number of E rosettes) and the clinical and histological changes detected during treatment with corticosteroids or immunosuppressants was studied. In most cases a correlation was found between clinical and histological activities and the intensity of immunological reactions. Immunological abnormalities usually preceded clinical exacerbations but were rarely seen in patients with stable remission. However, exceptions occurred, which limit the value of these tests as sole therapeutic guide-lines in systemic lupus erythematosus.
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