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N F Rothfield

Publications and source records attributed to N F Rothfield.

At least 55 records · Page 3Linked to original sources
PubMed1987

Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen.

We have isolated a series of overlapping cDNA clones for approximately 95% of the mRNA that encodes CENP-B, the 80-kD human centromere autoantigen recognized by patients with anticentromere antibodies. The cloned sequences encode a polypeptide with an apparent molecular mass appropriate for CENP-B. This polypeptide and CENP-B share three non-overlapping epitopes. The first two are defined by monoclonal antibodies elicited by injection of cloned fusion protein. Epitope 1 corresponds to a major antigenic site recognized by the anticentromere autoantibody used to obtain the original clone. Epitope 2 is a novel one not recognized by the autoantibody. These epitopes were shown to be distinct both by competitive binding experiments and by their presence or absence on different subcloned portions of the fusion protein. The third independent epitope, recognized by a subset of anticentromere-positive patient sera, maps to a region substantially closer to the amino terminus of the fusion protein. DNA and RNA blot analyses indicate that CENP-B is unrelated to CENP-C, a 140-kD centromere antigen also recognized by these antisera. CENP-B is the product of a 2.9-kb mRNA that is encoded by a single genetic locus. This mRNA is far too short to encode a polypeptide the size of CENP-C. The carboxy terminus of CENP-B contains two long domains comprised almost entirely of glutamic and aspartic acid residues. These domains may be responsible for anomalous migration of CENP-B on SDS-polyacrylamide gels, since the true molecular mass of CENP-B is approximately 65 kD, 15 kD less than the apparent molecular mass deduced from gel electrophoresis. Quite unexpectedly, immunofluorescence analysis using antibodies specific for CENP-B reveals that the levels of antigen vary widely between chromosomes.

Amino Acid Sequence↗
PubMed1986

High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients.

Patients with rheumatic diseases often have circulating autoantibodies to nuclear components. The clinical significance of the antibodies is controversial, although in some cases they are valuable in the diagnosis of the disease. This report presents results of a study of Scl-70, an autoantigen recognized by sera of many patients with the most severe form of progressive systemic sclerosis. It was possible to show, by three independent criteria, that Scl-70 is the abundant nuclear enzyme DNA topoisomerase I. Therefore, antibody probes of high titer and high affinity are now available for the study of this important nuclear enzyme.

Antibody Specificity↗
PubMed1986

Lack of induction of antinuclear antibodies by D-penicillamine in rheumatoid arthritis: a controlled study.

The induction of antinuclear antibodies (ANA) by D-penicillamine (DP) was studied in 148 patients with rheumatoid arthritis (RA) who had completed at least 30 weeks in a double blind trial which compared DP at doses 500 mg and 125 mg daily to placebo. There was no difference among the 3 groups in the frequency of a positive ANA at any titer or at a titer greater than 1:16 either pretreatment or at the end of the study. The conversion from a negative to a positive ANA occurred as frequently in the placebo treated controls with RA as in the DP treated RA patients. Antibodies to native DNA appeared in 3 DP treated patients, none of whom had symptoms of drug induced lupus or of DP toxicity.

Antibodies, Antinuclear↗
PubMed1985

A comparison of the specificity of the 1971 and 1982 American Rheumatism Association criteria for the classification of systemic lupus erythematosus.

The specificity of the preliminary and the revised American Rheumatism Association criteria for the classification of systemic lupus erythematosus (SLE) was tested in 207 of our patients with other rheumatic diseases which were considered to be important in the differential diagnosis of SLE. Using the preliminary criteria, the data revealed that 5 patients were falsely classified as having SLE (2 with scleroderma, 2 with Raynaud's disease, and 1 with systemic necrotizing vasculitis), whereas using the revised criteria, only 2 patients (1 with scleroderma and 1 with systemic necrotizing vasculitis) were falsely classified. The calculated specificity was 99% for the revised criteria and 98% for the preliminary criteria. Thus, the data revealed that the specificity of the revised criteria is high and comparable with that of the preliminary criteria when applied to a group of patients with related rheumatic diseases.

Adolescent↗
PubMed1984

The clinical utility of the lupus band test.

In order to determine the clinical utility of the lupus band test, the presence of dermal-epidermal junction (DEJ) deposits of IgG, IgM, IgA, C3, C4, Clq, and properdin were studied in biopsies of clinically normal deltoid area skin from 102 patients with systemic lupus erythematosus (SLE) and 151 patients with other rheumatic diseases. One or more proteins were detected at the DEJ in 72.6% (74 of 102) of patients with SLE and in 36.4% (55 of 151) of the other patients, yielding a specificity of 64% and a predictive value of 57%. The predictive value for the diagnosis of SLE was greatest with C4 (100%), properdin (91.3%), and IgA (86.2%) and lowest with IgM (59%). Specificity and predictive value increased with the number of proteins detected at the DEJ. The results suggest that more rigid criteria are required before diagnostic significance is attached to a positive result on the lupus band test.

Biopsy↗
PubMed1984

A comparison of the sensitivity of the 1971 and 1982 American Rheumatism Association criteria for the classification of systemic lupus erythematosus.

The sensitivity of the American Rheumatism Association's preliminary and revised criteria for the classification of systemic lupus erythematosus (SLE) was tested in 156 of our SLE patients. Eighty-eight percent met the 1971 preliminary criteria. Eighty-three percent fulfilled the 1982 revised criteria when arthritis was strictly defined (nonerosive arthritis) and 91% when arthritis was more liberally defined (nondeforming arthritis). Analysis revealed that of the 3 serologic tests added in the revised criteria (antinuclear antibody, anti-Sm, anti-DNA), the antinuclear antibody test accounted for the increased sensitivity of the revised criteria.

Follow-Up Studies↗
PubMed1983

Antibodies to native DNA and serum complement (C3) levels. Application to diagnosis and classification of systemic lupus erythematosus.

The sensitivity and specificity of the presence of antibodies to native DNA and low serum C3 levels were investigated in a prospective study in 98 patients with systemic lupus erythematosus who were followed for a mean of 38.4 months. Hospitalized patients, patients with other connective tissue diseases, and subjects without any disease served as the control group. Seventy-two percent of the patients with systemic lupus erythematosus had a high DNA-binding value (more than 33 percent) initially, and an additional 20 percent had a high DNA-binding value later in the course of the illness. Similarly, C3 levels were low (less than 81 mg/100 ml) in 38 percent of the patients with systemic lupus erythematosus initially and in 66 percent of the patients at any time during the study. High DNA-binding and low C3 levels each showed extremely high predictive value (94 percent) for the diagnosis of systemic lupus erythematosus when applied in a patient population in which that diagnosis was considered. The presence of both abnormalities was 100 percent correct in predicting the diagnosis os systemic lupus erythematosus. Both tests should be included in future criteria for the diagnosis and classification of systemic lupus erythematosus.

Adolescent↗
PubMed1983

Selective complete Clq deficiency associated with systemic lupus erythematosus.

We report a case of systemic lupus erythematosus (SLE) and recurrent infections associated with isolated Clq deficiency. A 17-year-old girl from Saudi Arabia was hospitalized with seizures, fever, arthralgia, hair loss, oral ulceration and skin rash. Clinical and laboratory findings fulfilled the ARA preliminary criteria for the classification of SLE. Nonlesional skin contained immunoglobulins and C3 at the dermal-epidermal junction. She did not have antibodies to DNA or low C3 or C4. Total serum hemolytic complement activity was absent due to a total selective absence of Clq. There was no circulating inhibitor of Clq activity. The published experience of isolated selective complete Clq deficiency associated with clinical disease is reviewed.

Adolescent↗
PubMed1982

The 1982 revised criteria for the classification of systemic lupus erythematosus.

The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.

Arthritis↗
PubMed1982

Partial H (beta 1H) deficiency and glomerulonephritis in two families.

H (beta 1H) controls the C3b amplification loop by its ability to displace Bb from the alternative pathway convertase, C3b,Bb, and acts as a cofactor with I (C3b inactivator) to produce inactive C3b. Serum C3 levels are dependent to a large extent on the levels of H and I. Partial H deficiency was found in two families. The index case in Family 1 had vasculitis, thrombocytopenia, proteinuria, and depressed serum H and C3 levels. The index case in Family 2 had depressed serum H and B (Factor B) levels and IgA nephropathy which progressed to renal failure. His sister also had IgA nephropathy and depressed serum H and C3 levels. The depressed serum C3 level, B level, and H level could be responsible for the development of the immune diseases found in some members of these families.

Adolescent↗
PubMed1982

Immunoglobulin M autoantibody to vimentin intermediate filaments.

Serum from a patient with the CREST Syndrome and systemic lupus erythematosus contained an IgM antibody that reacted at dilutions up to 1:800 with a fibrous cytoplasmic network in several epithelioid and fibroblastic cell lines. The antibody was shown by immunofluorescence microscopy to label a specific subset of cytoskeletal polymers, the intermediate filaments. The reactive antigen from this biochemically heterogeneous group of filaments was established as the 58,000-mol wt protein, vimentin: (a) the patient's serum reacts with a range of cell lines that contain intermediate filaments composed of vimentin, but not with cells whose intermediate filaments are composed of different protein subunits; (b) in PTK2 epithelioid cells the serum reacts with the class of filaments that coils around the nucleus after colchicine treatment (vimentin) and not with the filaments that remain dispersed after colchicine (prekeratin); and (c) the component of reactive cells that combines with the serum is shown by immunoelectrophoresis to be a 58,000-mol wt protein antigen. A similar antibody that binds intermediate filaments of PTK2 cells was encountered at lower titer in some sera from other patients with connective tissue diseases and in control sera. Previous routine antinuclear antibody assays using mouse liver or commercially prepared HEp-2 cells have failed to reveal anticytoskeletal antibodies in patient sera, perhaps due to inadequate presentation or preservation of cytoplasmic antigens.

Adult↗
PubMed1980

An epidemiologic study of households exposed to canine systemic lupus erythematosus.

To determine whether exposure to canine lupus is a risk for human lupus, we studied 83 members of 23 households exposed to 19 dogs with high titer antinuclear antibodies and compared these contact households to 50 members of 18 control households matched for dog age, sex, and primary veterinarian. No differences were found between contacts and controls in titer of antinuclear, antiDNA, antiRNA, and antilymphocyte antibodies, frequency of positive rheumatoid factor, or elevated serum immunoglobulins. Further analysis of subgroups by age, sex, and intensity of dog exposure did not reveal any serologic differences between contacts and controls. No cases of lupus were identified in either group. Three contact households and no controls reported a family history (remote from the household) of lupus. This study did not detect any clinical or serologic effect of human household exposure to dogs with high titer antinuclear antibodies.

Adolescent↗
PubMed1980

Familial discoid lupus erythematosus associated with heterozygote C2 deficiency.

Two siblings with chronic discoid lupus erythematosus and several family members were found with heterozygous C2 deficiency. An association with histocompatibility markers HLA-B18 and HLA-Dw2 was demonstrated, and the slow allotype of factor B was present. Linkage studies in this family suggested a close linkage between the C2 deficiency gene and genes coding for B18, Dw2, and BfS antigens. One HLA-ACB/DBf recombinant was observed showing closer linkage between HLA-D and Bf than between HLA-B and Bf.

Adolescent↗