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Biomedical subjects

M Reichlin

Publications and source records attributed to M Reichlin.

At least 199 records · Page 11Linked to original sources

Unusual cutaneous manifestations of systemic lupus erythematosus: I. Urticaria-like lesions. Correlation with clinical and serological abnormalities.

Ten of 143 systemic lupus erythematosus patients demonstrated urticaria-like lesions. Lesional biopsies in 7 of 9 patients tested revealed a leukocytoclastic angiitis and in 2, a mononuclear perivascular infiltrate. Direct immunofluorescent studies in 2 of 6 patients tested revealed IgM and C3 deposition in and about dermal blood vessels. Nine of the 10 systemic lupus erythematosus, patients displayed active clinical disease (e.g., arthritis, renal disease, etc.), a positive lupus band test, antibodies against deoxyribonucleic acid or Sm macromolecules, serum hypocomplementemia and markedly elevated quantities of serum immune complexes as determined by an immunoradiometric assay employing Raji cells. Similar lesions were not detected in 35 discoid lupus erythematosus patients. These studies strongly suggest: (1) urticaria-like lesions are uncommon cutaneous manifestations of systemic lupus erythematosus. (2) These urticaria-like lesions do not represent a classic IgE mediated urticaria. (3) These urticaria-like lesions generally occur in lupus erythematosus patients demonstrating clinical and/or serological evidence of systemic disease activity. (4) These lesions are probably secondary to immune complex deposition. We, therefore, conclude that all urticarial lesions in lupus erythematosus patients should be biopsied and the patient evaluated for active systemic disease.

Antibodies, Antinuclear↗

Lupus band test in untreated SLE patients: correlation of immunoglobulin deposition in the skin of the extensor forearm with clinical renal disease and serological abnormalities.

This study demonstrated that 88% of untreated systemic lupus erythematosus patients with clinical renal disease displayed the deposition of immunoglobulin and complement at the dermal epidermal junction of the noninvolved light exposed extensor surface of the upper 1/3 of the forearm (P less than 0.005) (positive lupus band test). Eighty-five percent of these untreated systemic lupus erythematosus patients with anti-deoxyribonucleic acid antibodies (native and/or single stranded) (P less than 0.001) and 96% of systemic lupus erythematosus patients with hypocomplementemia had a positive lupus band test (P less than 0.001). Those systemic lupus erythematosus patients with a negative lupus band test or a positive lupus band test composed of pure IgM had a decreased incidence of renal disease, serum hypocomplementemia and anti-DNA antibodies. Their sera, however, frequently contained antibodies directed against nuclear ribonuclear protein or against the cytoplasmic non-nucleic acid glycoprotein termed Ro. On the contrary, 85% of systemic lupus erythematosus patients with a positive lupus band test composed solely or in part of IgG, had anti-DNA antibodies (P less than 0.001). Their sera also frequently contained anti-Sm antibodies. The lupus band test was found to be dynamic. In general, the appearance as well as the disappearance or the marked decrease in intensity and complexity of a positive lupus band test was found to correlate with disease exacerbation, remission and the appearance and disappearance of DNA antibodies and serum hypocomplementemia.

Antibodies, Antinuclear↗

Rapid radioimmunoassay for serum myoglobin.

A rapid radioimmunoassay for serum myoglobin concentration has been developed, capitalizing on a technique for rapid separation of antibody-bound antigen from free antigen using Sepharose-bound sheep anti-rabbit gamma-globulin. Total time required for the assay is 2.75 h, making it suitable for clinical approaches employing myoglobin for rapid identification of patients in the active phase of myocardial injury.

Humans↗

Deposition of antibodies to a soluble cytoplasmic antigen in the kidneys of patients with systemic lupus erythematosus.

Two patients with systemic lupus erythematosus were studied whose sera contained precipitating antibodies to a soluble cytoplasmic antigen, termed Ro. A reduction in the amount of these antibodies in each case was accompanied by a deterioration in the clinical status with the development of nephritis leading to death. Acid elution of gamma globulin was performed from homogenates of the renal cortex, and in both instances antibodies to Ro were demonstrated in the eluates by double immunodiffusion. The titer of these antibodies was measured in both sera and eluates, and specific enrichment of anti-Ro in the eluates was demonstrated in both patients. This strongly suggests the direct participation of Ro-anti-Ro immune complexes in the progressive renal disease and may underlie the association seen here between the decreasing serum titers of antibodies to Ro and the clinical deterioration in these two cases.

Antibody Specificity↗

Occurrence of antibodies to single-stranded DNA in ANA negative patients.

Five patients with clinical features of a connective tissue disease most suggestive of systemic lupus erythematosus were found to have a negative ANA by conventional screening at 1/20 dilution on mouse liver. However, significant titres of antibodies to single-stranded DNA were detected using a double antibody radioimmunoassay. Thus, certain patients have antibodies to DNA restricted to single-stranded determinants as detected by radioimmunoassay with single-stranded DNA as antigen and a negative ANA test.

Antibodies↗

Idiotypic cross-reactivity between antibodies of different specificities.

Cross-idiotypic specificity has been demonstrated between antibody populations of different specificities using antibodies directed toward human sickle cell hemoglobin (HbS). A site-specific antibody directed toward the beta6-position of HbS, anti-Val, was used to elicit an anti-idiotypic response in rabbits. Using this anti-idiotypic serum, idiotypic cross-reactivity was demonstrated between antibody populations that bind to human adult hemoglobin (HbA). It was demonstrated that in the case of the goat antibodies, these idiotypically cross-reacting antibodies are directed towards the beta6-position of the hemoglobin molecule. However, they differ in their specificity, binding to this site on HbA, whereas anti-Val binds only to HbS. The sheep antibody populations directed toward HbS differ qualitatively from those of the goat. Using rabbit anti-idiotypic serum specific for sheep anti-Val, cross-reactivity could be demonstrated with antibodies directed toward the alpha-chain of the hemoglobin molecule, as well as the beta-chain. There was also a low level of cross-reactivity with antibodies from a goat immunized with HbA.

Animals↗

Radioimmunoassay for human myoglobin. Initial experience in patients with coronary heart disease.

A radioimmunoassay for human myoglobin has been used to study the serum myoglobin level in 13 normal individuals and 68 patients admitted to a Coronary Care Unit because of chest pain. Values in normal individuals ranged from 3 to 75 and averaged 25 +/- 23 (SD) ng/ml. Thirty-two patients with myocardial infarction initially examined within 12 hours of the onset of chest pain all showed clear-cut elevations in serum myoglobin, peak values ranging from 200 to 5500 and averaging 1368 +/- 1357 ng/ml. Seventeen patients with clinically atypical chest pain and no subsequent evidence of myocardial necrosis had myoglobin levels in the normal range, as did 11 of 19 patients with chest pain thought clinically to represent myocardial ischemia but no subsequent evidence of myocardial necrosis by conventional criteria. The final eight patients in the latter group showed mild elevations of serum Mb, peak values ranging from 102 to 280 and averaging 162 +/- 52 ng/ml; the basis for these elevations remains to be clarified.

Animals↗

Acute renal failure secondary to interstitial lupus nephritis.

A patient with systemic lupus erythematosus (SLE), followed up over a six-month period, exhibited numerous immunologic abnormalities and varied renal pathologic features. Initial findings included minimal glomerular lesions, serum antibodies directed solely against nuclear RNA protein, and lupus band test showing pure IgM deposition. These findings suggested a good prognosis. Subsequently, the patient developed acute renal failure secondary to an interstitial lupus nephritis, without progression of the glomerular abnormality. Serum antibodies to the nuclear non-nucleic acid macromolecule and single stranded and native DNA were demonstrated concurrently. New skin deposits of IgG and IgA in addition to IgM also were observed. This patient demonstrates the potential progression of lupus renal disease despite the initial favorable prognostic indicators.

Acute Kidney Injury↗

Patterns of clinical disease associated with antibodies to nuclear ribonucleoprotein.

Forty-three patients were studied whose sera were monospecific for nuclear ribonucleoprotein by double immunodiffusion. Thirty-four patients had features typical of systemic lupus erythematosus of which 30 fulfilled the American Rheumatism Association criteria. Clinical features such as rashes, serositis and hematological abnormalities occurred with a frequency expected in SLE. Raynaud's phenomenon occurred in 60%, but other features of mixed connective tissue disease were uncommon. Clinical evidence of renal disease occurred in only four patients. In our experience a good prognosis is related more to the presence of anti-nRNP alone in the serum than to any specific set of clinical findings.

Antibodies, Antinuclear↗

Specific antibodies to hemoglobin A1 (anti-Glu) and hemoglobin S (anti-Val) in the guinea pig: immunologic and structural correlations.

Like goats and sheep, guinea pigs can produce, in response to human sickle cell hemoglobin (beta6 Glu leads to Val), an antibody population (anti-Val) that will bind sickle cell hemoglobin but not normal hemoglobin HbA. Unlike goats and sheep, guinea pigs can produce in response to human hemoglobin A1 an antibody fraction, anti-Glu, that will not react with human sickle cell hemoglobin. These anti-Glu antibodies have been isolated by affinity chromatography and their specificity confirmed by fluorescence-quenching titrations. The sequence of the first 10 amino acids of the beta-chain of guinea pig hemoglobin has been determined. This sequence differs from those of both hemoglobin HbA and sickle cell hemoglobin by two residues, those at positions 5 and 6. This explains the similarity of the immunogenicity of this site on the two human hemoglobins when administered to guinea pigs. Both goats and sheep are identical to hemoglobin A1 at the beta-6 position.

Amino Acids↗

Evolution of an idiotypic determinant: anti-Val.

An antibody population which reacts only with human sickle cell hemoglobin (HbS) and not with normal human hemoglobin, has been isolated from goat, sheep, and guinea pig antisera. These antibody populations termed anti-Val (Val), isolated from an individual goat (no. 6) and sheep (no. 26) have been used to elicit anti-idiotypic responses in rabbits. These anti-idiotypic sera were used to study the idiotypic cross-reactions between the goat and sheep anti-Val. Strong cross-reactions were present using either Ra anti-goat anti-Val or Ra anti-sheep anti-Val. Guinea pig anti-Val did not cross-react with these anti-idiotypic sera. Binding of HbS to the anti-Val of the goat and sheep could be blocked by the anti-idiotypic sera, but the binding of HbS to the guinea pig anti-Val could not. These data demonstrate idiotypic cross-reactivity between two closely related species.

Animals↗

Quantitation of precipitating antibodies to certain soluble nuclear antigens in SLE.

Electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulfate was used to separate and quantitate the components of a washed immune precipitate. Serum was from patients with systemic lupus erythematosus known to have antibodies to soluble nuclear ribonucleoprotein (RNP) or to a soluble nuclear non-nucleic acid protein (Sm). Amounts of antibody that was predominantly IgG ranged from 0.2 to 8 mg/ml of patients' serum, and in some cases accounted for over 20% of the total serum IgG. Results demonstrate that some patients respond to the disease by producing large amounts of a specific antibody, and that these antibodies can contribute significantly to hypergammaglobulinemia.

Antibodies, Antinuclear↗