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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 739 records · Page 41Linked to original sources

Human monoclonal antibodies derived from pleural effusion lymphocytes of a patient with breast carcinoma react with human breast cancer-associated antigens and mouse mammary tumor virus polypeptides.

Four human hybridoma cell lines (PEB1-4) were established from a fusion of pleural effusion lymphocytes isolated from a breast cancer patient with metastatic disease, 6 years postmastectomy. The hybridomas secreted IgG-k (3 micrograms/ml/10(6) cells). These monoclonal antibodies (PEB1-4) reacted to different degrees with mouse mammary tumor virus (MMTV) and T47D particles (HuMTV). Immunological cross-reaction was also detected with antigens isolated from body fluids of breast cancer patients (BF-Ag). The binding capacity of the monoclonal antibodies (MAbs) PEB1-4 to the above-mentioned antigens was measured by RIA. The specificity of these antibodies was further demonstrated by radioimmunoprecipitation of MMTV, T47D (HuMTV) and BF-Ag. The binding of PEB1-4 to surface antigens of intact cells grown in culture was measured by RIA. Some of the MAbs were shown to bind more avidly to breast cancer cells than to nonbreast cancer cells or nonmalignant cells. The PEB1-4 human monoclonal antibodies may be found useful in analyzing the virus-breast cancer relationship.

Aged↗

Low serum antimycobacterial glycolipid antibody titers in the sera of patients with systemic lupus erythematosus associated with central nervous system involvement.

Antibodies which bind to glycolipids derived from Mycobacterium tuberculosis were sought in the sera of patients with systemic lupus erythematosus (SLE), with and without neurological disease, patients with active tuberculosis and normal controls. A significantly lower activity against the mycobacterial glycolipids was detected in the sera of patients with SLE with neurological involvement compared to other patients with SLE or controls. We suggest that low antibody levels against mycobacterial glycolipids may be useful in the diagnosis of patients with SLE in whom involvement of the central nervous system is suspected.

Antibodies, Bacterial↗

A common anti-DNA idiotype and other autoantibodies in sera of offspring of mothers with systemic lupus erythematosus.

Since the immune response in fetuses of mothers with systemic lupus erythematosus (SLE) is unknown, we investigated sera from six mothers and their paired offspring by enzyme-linked immunosorbent assay (ELISA) for the presence of a common anti-DNA idiotype (16/6 Id) and, as control, for the presence of an unrelated public idiotype of antibody to hepatitis B surface antigen (HBsAg). In addition, maternal as well as fetal sera were evaluated for the presence of antibodies to ssDNA, dsDNA, poly(I), poly (dT), RNA, cardiolipin, total histones and the presence of lupus anticoagulant. Clinically active SLE mothers showed in general increased IgG and, to a lesser extent, IgM autoantibody activity. Circulating lupus anticoagulant was detectable in clinically active mothers only. All offspring of clinically active SLE mothers showed increased IgG autoantibodies to a variety of antigens, while IgM antibodies were detected in only one fetus. In contrast, fetuses of clinically inactive mothers showed only minor IgG activity. Common anti-DNA-idiotype (16/6 Id) activity also correlated with disease activity in both maternal and fetal compartments. One clinically active mother was 16/6-negative; her offspring was, however, positive, indicating de novo production of the idiotype by the fetus. In contrast, a control anti-HBsAg idiotype was not detected in either maternal or fetal sera. It therefore appears that offspring of clinically active SLE mothers serologically reflect maternal disease activity. Furthermore, autoantibodies and common idiotype of autoantibodies can be found within the fetal compartment even in the absence of such antibodies in the maternal serum. Discrepancies between mothers and offspring in IgM-autoantibody levels and the presence of new idiotypes in fetuses are indicative of fetal de novo autoantibody production.

Adult↗

The sera of patients with Klebsiella infections contain a common anti-DNA idiotype (16/6) Id and anti-polynucleotide activity.

In view of recent reports linking Klebsiella pneumoniae with autoimmunity, we have examined the sera of 52 patients with urinary tract infection or septicaemia from this Gram-negative pathogen, for the presence of antibodies to DNA, polynucleotides, cardiolipin and a common anti-DNA idiotype 16/6. Up to 27% of these patients had anti-polynucleotide antibodies detectable, and in 37% the 16/6 idiotype was found. Absorption of the sera of two patients, with no DNA binding, against the Klebsiella polysaccharide K-30 induced a significant fall in both their anti-K30 antibody and 16/6 idiotype levels. Among 52 patients with other Gram negative infections a maximum of 17% and 19% respectively, had anti-DNA antibodies and the 16/6 idiotype present in their serum. In 37 normal controls, the rate of antibody and idiotype detection was 5% or less. The presence of autoantibodies in the serum of patients with Klebsiella infections may be the result of non-specific stimulation due to bacterial polyclonal activation. However, there might also be a specific stimulus triggered by idiotypic cross-reaction between autoantibodies and anti-Klebsiella antibodies.

Adult↗

ELISA measurement of antibody titer to purified protein derivative and mycobacteria-derived phosphoglycolipids: tool for diagnosing active pulmonary tuberculosis.

There is a continuous search for a rapid, efficient and reliable serodiagnostic technique for active tuberculosis (TB). Using ELISA (enzyme-linked immunosorbent essay) we have determined antibodies reactive to purified protein derivative (PPD) and two phosphoglycolipids extracted from Mycobacterium bovis cell wall, phosphatidyl inositol dimannoside (PID) and phosphatidyl inositol pentamannoside (PIP). Twenty-one patients of Ethiopian origin with active pulmonary TB and 20 healthy control subjects vaccinated with BCG in infancy were evaluated. A significantly higher level of immunoglobins reactive with the antigens was found among the patients with active pulmonary TB. The mean +/- SD of the OD units (x 10(3)) recorded in the sera of TB patients compared with control subjects were as follows: using PPD 250 +/- 210 vs. 120 +/- 150 (P less than 0.025); with PID 1,150 +/- 470 vs. 750 +/- 150 (P less than 0.01); and with PIP 1,170 +/- 500 vs. 780 +/- 160 (P less than 0.025). Accordingly, the sensitivity and specificity levels were: with PPD 81 and 75%, with PID 82 and 80% and with PIP 73 and 70%, respectively. Much more accuracy can be obtained by calculating the results of reactivity toward the combined free antigen assays. It is suggested that ELISA using mycobacterial derived antigens might be useful in the diagnosis and screening of active pulmonary TB in large populations, due to its rapidity and simplicity.

Antibodies, Bacterial↗

Placental type isoferritins in chronic liver diseases.

Serum ferritin levels in chronic liver diseases were measured by an enzyme-linked immunosorbent assay (ELISA) using two monoclonal antibodies (McAb) against placental ferritin. One of the McAbs (CM-H9) recognizes a specific placental-like isoferritin (PLF) only, while the other McAb (CM-G8) recognizes an isoform (CF) common to human placenta, liver and spleen. The different diseases studied were primary biliary cirrhosis (PBC-14 patients), chronic active hepatitis (CAH-12 patients), alcoholic cirrhosis (AC-18 patients) and cryptogenic cirrhosis (CRY-26 patients). Increased levels of both isoferritine were found in all these liver disorders, with an overall incidence of 80% for CF and 40% for PLF. The mean level of CF was significantly above normal in PBC, AC and CRY and that of PLF in PBC and CRY. Circulating placental-type isoferritins have not been previously described in patients with liver disorders. Our findings indicate that elevation of serum ferritin in liver diseases is caused by different isoferritin components.

Antibodies, Monoclonal↗

Leukocytosis in non hematological malignancies--a possible tumor-associated marker.

Leukocytosis (WBC counts 10,000/mm3) was detected in 77 out of 252 patients (30%) with ten different types of nonhematological malignancy (NHM) at the time of diagnosis. A full search including serological and bacteriological screening was performed to exclude other possible causes of leukocytosis. Among the different tumors, carcinomas of the lung and colorectum were the most prevalently associated with leukocytosis. Absolute monocytosis was found in 25% of the patients and absolute eosinophilia in only 4.8%. The leukocytosis was attributed mainly to an increase in the mature polymorphonuclears, suggesting a release mechanism of WBC from storage pools by factors secreted or induced by the tumor. Neither the age nor the sex of the patients affected the incidence or magnitude of leukocytosis. However, the presence of metastases was associated with a significantly higher incidence of leukocytosis (p less than 0.05). The associated leukocytosis may be regarded as a poor prognostic sign, and was associated with a significantly (p less than 0.007) shorter survival time. In contrast, absolute lymphocytosis may have a positive effect on the survival time (p = 0.01). Tumor-associated leukocytosis may be an additional tumor-associated marker, of value in assessing and monitoring patients with NHMs.

Female↗

The detection of a common idiotype of anti-DNA antibodies in the sera of patients with monoclonal gammopathies.

The sera of 265 patients with monoclonal gammopathies were examined for the presence of a dominant idiotype of the anti-DNA antibody [16/6 idiotype (Id)] and for anti-DNA activity. An enzyme-linked immunosorbent assay (ELISA) with a rabbit anti-16/6 antibody revealed 23 (8.7%) sera that contained increased concentrations of the idiotype. Seven of the patients had benign monoclonal gammopathy, three multiple myeloma, three Waldenström macroglobulinemia, five essential mixed cryoglobulinemia, and five monoclonal cryoglobulinemia. In 5 of the 23 sera, antinuclear activity was also noted. In 11 of the 16/6 Id-positive sera the anti-nucleic acid antibody reactions were found to be polyspecific, reacting with polydeoxythymidilic acid and polyinosinic acid, in addition to single-stranded DNA and double-stranded DNA. Similar results were achieved with the purified serum monoclonal components. The specificity of the idiotype analysis was demonstrated with an unrelated dominant idiotype of anti-HBsAg antibody. In none of the patients, except one (with essential mixed cryoglobulinemia), was lupus symptomatology noted.

Antibodies, Anti-Idiotypic↗

Preferential secretion of a common anti-DNA idiotype (16/6 Id) and anti-polynucleotide antibodies by normal mononuclear cells following stimulation with Klebsiella pneumoniae.

Peripheral blood mononuclear cells derived from 6 normal subjects were incubated with 5 polyclonal activators (pokeweed mitogen, Epstein-Barr virus, group-A Streptococcus, Staphylococcus aureus and Klebsiella pneumoniae. After 7 days of incubation, the supernatants were examined for immunoglobulin (IgG and IgM) production, the level of a common anti-DNA idiotype (16/6 Id) and autoantibody activity against ssDNA, dsDNA, poly(I), poly(dT) and cardiolipin. Significantly increased levels of the 16/6 Id were recorded only with the Klebsiella stimulated MNC. Increased immunoglobulin levels and autoantibody reactivity were noted with all 5 polyclonal activators. The Klebsiella cell membrane preparation induced the highest values. No correlation was found between the 16/6 levels, autoantibody activity and the absolute concentrations of IgG or IgM. This study, together with previous reports, suggests a role for Klebsiella in the etiology of autoimmune diseases. We suggest that Klebsiella can induce anti-DNA-like autoantibodies not only by polyclonal activation, but also by a more specific stimulus.

Autoantibodies↗

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.

Adolescent↗

Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus.

The lupus anticoagulant (LA) is an acquired autoantibody of the IgG or IgM type that acts on platelet factor III, inhibiting the generation of the prothrombin activator complex. It is prevalent in 5-10% of SLE cases and, in contradistinction to the name anticoagulant, it may be associated with thrombotic events, recurrent abortion or intrauterine death. Anti-cardiolipin antibody like LA, is an anti-phospholipid antibody and also causes recurrent thrombotic events. Mention has been made of a possible cross-reactivity between anti-phospholipid antibodies and anti-DNA antibodies. The optimal treatment for this problem is at present unknown.

Antibody Specificity↗

Autoantibodies, idiotypes, anti-idiotypes and autoimmunity.

The establishment of mouse and human monoclonal anti-DNA antibodies is described. Common idiotypes were identified on these antibodies employing monoclonal (mouse) and polyclonal anti-idiotypic antibodies. The significance of the presence and titer of the common idiotypes as clinical activity marker was examined in patients with systemic lupus erythematosus. Based on Jerne's network theory [Ann. Immunol. 125c: 373-389, 1974], naturally occurring anti-idiotypic antibodies to anti-DNA antibodies were reported. The utilization of this information to understand autoimmunity is discussed.

Amino Acid Sequence↗

High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE.

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.

Autoantibodies↗

Scabies-associated angioimmunoblastic lymphadenopathy.

A systemic disorder characterized by fever and reactive lymphadenopathy developed in a patient with scabies infestation. Regression of all clinical symptoms and signs occurred after antiscabies therapy. Two months later, the whole clinical picture reappeared concomitantly with scabies reinfestation. Subsequent lymph node biopsy demonstrated typical angioimmunoblastic lymphadenopathy (AILD). It is plausible that persistent antigenic stimulation caused by scabies infection was of pathogenetic importance in the induction of the syndrome of AILD. Infectious agents should be considered and looked for in patients with AILD, since they may play a role in the evolution of this disease.

Aged↗

Monoclonal anti-tuberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis.

Classical models of experimental autoimmune diseases, such as adjuvant arthritis entail the use of mycobacteria. Furthermore, BCG immunotherapy may be followed by arthritic symptoms. To test the infection-autoimmunity relationship of mycobacteria, we used monoclonal antibodies raised against M. tuberculosis and against DNA. Murine monoclonal anti-TB antibodies were found to react with ssDNA, dsDNA and other polynucleotides. Monoclonal anti-DNA autoantibodies derived from patients and mice with SLE bound to three glycolipids shared among all mycobacteria and derived from mycobacterial cell wall. Prior incubation of the antibodies with ssDNA and other polynucleotides or with glycolipid antigens inhibited binding. These results indicate that infecting mycobacteria share antigens with human tissue, thus accounting in part for the production of autoantibodies in mycobacterial infections.

Animals↗