Biomedical subjects
Publications and source records attributed to M Reichlin.
Antibodies reactive with rabbit cytochrome c have been observed in rabbits immunized with several heterologous cytochromes. Such antibodies have also been observed in rabbits immunized with rabbit cytochrome c conjugated to bovine gamma globulin. The serum of a rabbit immunized with human cyto chrome c reacted with the cytochrome c of the same rabbit.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Seven patients with classic cutaneous lupus erythematosus are described. Three of these patients had features satisfying four of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of systemic lupus erythematosus (SLE). Their sera, however, lacked antinuclear antibodies but demonstrated precipitating antibodies reactive against cytoplasmic RNP (La) and non-nucleic acid (Ro) antigens. Four additional ANA-negative patients lacking significant skin disease but having a lupus-like multisystem disease were found to have antibodies to soluble cytoplasmic antigens. Thirty-three of 130 ANA-positive SLE patients, but none of 16 discoid lupus patients, possessed these anticytoplasmic antibodies. These findings suggest that antibodies to Ro and La may be a marker for systemic disease in ANA-negative patients with 1) cutaneous lupus and 2) a distinct subpopulation of patients with a lupus-like syndrome without skin disease.
Radioimmunoassay of serum myoglobin was done in 53 patients with polymyositis syndromes and other conditions. Serum myoglobin values in 33 healthy subjects ranged from 4 to 77 [mean 33.3 +/- 19.8 (SD)] ng/ml. Fifty percent of polymyositis patients had elevated serum myoglobin levels (greater than 80 ng/ml). Serum myoglobin values in polymyositis patients fluctuated more sensitively than CPK and GOT. Combined estimation of myoglobin and CPK offers advantages for the detection of muscle injury and the prediction of disease exacerbation.
Explore the source record for details and available documents.
Glomerular deposits of immunoglobulin A (IgA) (and immunoglobulin G [IgG]) has been described in IgA-nephropathy (Berger's disease), in anaphylactoid purpura, and systemic lupus erythematosus. The pathogenesis of mesangial IgA deposits in these disease states is unclear. Circulating immune complexes have been speculated to be involved although their existence in blood in IgA nephropathies have never been reported. We describe a 53-year-old man who presented with a petechial rash in lower extremities accompanied by painful swelling of left ankle and wrist. Polyclonal elevation of IgA and IgG in serum was found, along with cryoglobulins containing IgA and IgG (rheumatoid factor positive). After two years, hematuria, mild proteinuria, and active urinary sediment developed and renal biopsy revealed focal proliferative changes. Immunofluorescence revealed predominantly mesangial deposits of IgA and IgG but no IgM nor complement. This experience suggests that circulating complexes consisting of IgA and IgG may lead to renal lesions presenting clinically and histologically in a way similar to that commonly seen in IgA nephropathies.
Explore the source record for details and available documents.
Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints.
Antibodies to Jo-1, a saline extractable nuclear antigen, were found in 11/47 (23%) patients with myositis and in 0/35 controls with systemic lupus erythematosus or progressive systemic sclerosis (p less than or equal to 0.01). Within myositis subgroups, anti-Jo-1 occurred in 6/20 (30%) with polymyositis, 2/16 (13%) with dermatomyositis and 3/7 (43%) with overlap. There was an association between Jo-1 antibodies and HLA-DR3, irrespective of race or clinical subgroups (p less than or equal to 0.05). All anti-Jo-1 positive patients had either HLA-DR3, HLA-DRW6 or both (p less than or equal to 0.01). Thus, this antibody system might arise as a result of an aberrant immune response mediated at or near HLA-D in patients with myositis.
Eighty-eight untreated systemic lupus erythematosus patients collected from rheumatology services were studied for the presence of discoid, molar and vasculitic lesions and photosensitivity. Their sera were examined for antibodies to native deoxyribonucleic acid (nDNA), nuclear ribonuclear protein (nRNP), the non-nucleic acid nuclear macromolecule Sm, the nuclear and cytoplasmic macromolecules La(SSB) and the predominantly cytoplasmic macromolecule Ro(SSA). These studies demonstrated that 42% of the lupus patients possessed nDNA; 36% nRNP; 24% Ro(SSA) and 9% anti La(SSB) antibodies. Six patients failed to demonstrate significant antinuclear antibody titers (mouse liver substrate), and 4 of these possessed anti Ro(SSA) antibodies. Correlation to the cutaneous lesions among this lupus population possessing various serum antibodies revealed a trend toward photosensitivity and molar dermatitis in the Ro(SSA), La(SSB), Ro/la and the ANA negative, ANA negative/Ro positive groups of lupus patients.