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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 595 records · Page 33Linked to original sources
PubMed1991

[Antinuclear antibodies in IgA nephropathy, as well as mesangiocapillary and membranous glomerulonephritis].

IgA nephropathy, assumed to be a form of chronic immune complex glomerulonephritis, has sometimes been associated with various autoimmune diseases and autoimmune phenomena including autoantibody production. The present study was aimed at thoroughly investigating the frequency of autoantibodies against five common nuclear autoantigens in 59 patients with IgA nephropathy and in 48 patients with other immune complex glomerulonephritides (24 patients with membranous and 24 with mesangio-capillary glomerulonephritis) and in 30 healthy controls. The incidence of raised autoantibody titres (greater than or equal to 2 SD of the average of controls) in IgA NP was not found to be significantly different from the incidence of other immune complex glomerulonephritis groups. In none of the subjects was a titer above 3 SD of the average of controls found. Although IgA NP is thought to be an immune mediated disease, on the basis of our study it is not associated with a statistically significant incidence of raised antinuclear antibodies.

Antibodies, Antinuclear↗
PubMed1991

[Neurologic complications of primary Sjogren's syndrome].

Primary Sjogren's syndrome has a wide clinical spectrum, ranging from an exocrinopathy to a systemic process and even extending to B-lymphocyte neoplasia. We describe a patient with this syndrome who developed central nervous system involvement manifested by involuntary dystonic movements of the mouth and larynx. We believe that the neurological involvement in this patient is part of his basic disease. Further studies are required to define more accurately the frequency, severity and spectrum of the neurological manifestations associated with primary Sjogren's syndrome.

Central Nervous System Diseases↗
PubMed1991

Pathogenic anti-DNA idiotype (16/6 Id) in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is regarded as a classical autoimmune disease. Despite this belief, no one has been able to induce the disease in naive animals, neither with DNA nor with anti-DNA antibodies. We report on the induction of SLE in BALB/c mice following immunization with a pathogenic anti-DNA idiotype (16/6 Id) or its anti-Id. We also report on a specific treatment with T suppressor cells specific for the 16/6 Id. The induction of SLE in naive mice with a pathogenic anti-DNA Id suggests an additional mechanism for the diversity of manifestations in this disease.

Animals↗
PubMed1991

Anti-pyruvate dehydrogenase autoantibodies in primary biliary cirrhosis.

Antimitochondrial antibodies (AMA) may be detected in 95% of patients with primary biliary cirrhosis (PBC). The target autoantigens for the AMA were recently identified as four closely related metabolic enzymes located in the mitochondria. We have purified the pyruvate dehydrogenase (PDH) enzyme from bovine heart, showing that all PBC sera reacted with a 74-kd band. PDH was utilized to establish an ELISA assay for detecting the relevant antibodies. One hundred twelve of 120 sera from patients with PBC (95%) reacted with the PDH but none of the 201 control sera, including normal subjects and a panel of sera from other patients with liver diseases, showed similar reactivity. In 77% of the PBC sera the anti-PDH antibody isotype was identified as a combination of IgG and IgM, while in 18% only IgM was detected. In 5% of the sera the isotype was confined to IgG. PBC sera specifically inhibited the PDH enzyme activity. The enzyme inhibition correlated with the anti-PDH antibody titers. Thus, PDH seems to be one of the major target epitopes for AMA observed in sera of patients with PBC.

Animals↗
PubMed1991

Effects of aging on the induction of experimental systemic lupus erythematosus (SLE) in mice.

The study was designed to determine whether manifestations of autoimmunity are altered with age, using an experimental model in which systemic lupus erythematosus (SLE) is induced in mice. Young (2-month-old), and aging (18-month-old) BALB/c female mice were immunized with a human monoclonal anti-DNA antibody that bears a common idiotype (16/6 Id). Control groups were either left untreated or were injected with human IgM (HIgM). Anti-16/6 Id levels were found to be significantly lower in the old mice than in the young. Similarly, anti-anti-16/6 Id (murine 16/6 Id+) values were lower in the old. Mice injected with the 16/6 Id also produced various autoantibodies, including anti-dsDNA, anti-RNP, anti-Sm and anti-histones antibodies. The levels of these antibodies were lower in the old mice than in the young, yet the differences were not statistically significant. Levels of autoantibodies examined in control animals were either similar in both age groups (anti-RNP and histones) or lower in the old (anti-dsDNA and Sm). Four months after a booster injection of 16/6 Id, the young mice developed clinical manifestations of SLE, including proteinuria and leukopenia, which were seen, in milder form, in the aged mice. Immune complex depositions examined by immunohistology on kidney sections suggested similar differences based on the age of the animals. Our results suggest that aging might actually be associated with a decline in the capacity to produce autoimmune responses.

Aging↗
PubMed1991

Induction of systemic lupus erythematosus in naive mice with T-cell lines specific for human anti-DNA antibody SA-1 (16/6 Id+) and for mouse tuberculosis antibody TB/68 (16/6 Id+).

Previously we have shown the ability to induce experimental systemic lupus erythematosus (SLE) in naive mice with pathogenic antibodies carrying the 16/6 idiotype (Id) and with the T-cell line specific for the 16/6 Id. In the present study we established and characterized a series of T-cell clones that react against diverse autoantibodies carrying the 16/6 Id and show that they are capable of inducing a SLE-like disease in mice. The T-cell clones were generated from BALB/c mice immunized with the human mAb anti-DNA antibody (SA-1) and the mouse monoclonal anti-tuberculous Ab (TB/68), both carrying the 16/6 Id. The T-cell clones proliferated only in the presence of either human or mouse mAb carrying the 16/6 Id. All the T-cell clones were found to be of the helper type (L3T4) and were H-2 restricted in their function. The injection of the clones to BALB/c mice resulted in serological findings (e.g., anti-DNA, anti-Sm), clinical manifestations (e.g., proteinuria, low white blood cell counts, increased erythrocyte sedimentation rate), and renal insult typical of SLE disease. Our data support the role attributed to pathogenic idiotypes in SLE on the one hand and that played by cellular immunity on the other. The mechanism by which Id-specific T-helper cells may induce SLE is currently not clear. The immunogenicity of the T-cell receptor (anti-16/6) and the cells themselves acting as effector/helper cells, thus leading to damage, may play a role in initiating a chain of events that ends in the production of a panoply of autoantibodies, some of which may also have a regulatory function.

Animals↗
PubMed1991

Autoantibodies in male homosexuals and HIV infection.

We have used ELISA to study the frequency of autoantibodies to several antigens in the serum of 17 male homosexuals (MHS) negative for HIV (HIV-), 11 asymptomatic HIV seropositive MHS (HIV+) and patients with ARC (N = 15) or AIDS (N = 13), and compared them to 20 matched healthy heterosexual controls. Serum antibody binding to histones, cardiolipin, ss-A, ss-B and Sm was found to be significantly higher in each of the MHS groups studied as compared to controls (P less than 0.001), and was also increased in the HIV+ patients vs. the HIV- group (P less than 0.05). In contrast, no increase in autoantibodies to ss-DNA, ds-DNA, poly(I), poly(G) or RNP were found in any of the groups tested. These results enlarge the spectrum of autoimmunity previously reported in HIV infection and identify a similar pattern to a lesser degree, already present in HIV- MHS, suggesting a role for HIV or concomitant virus infections in its pathogenesis.

AIDS-Related Complex↗
PubMed1991

The production of human monoclonal anti-MMTV antibodies by in vitro immunization with anti-idiotypic antibodies.

We have previously reported the production of a series of human monoclonal antibodies reacting with mouse mammary tumor viral antigens as well as the human counterpart HuMTV antigen. Against two of these antibodies (B11 and 4.6/6), anti-idiotypic antibodies were generated, which appeared to be the internal image of viral antigen. Vaccination with the anti-idiotypic antibodies induced in mice humoral and cellular immunity against both MMTV and HuMTV. The current study describes a novel method to produce human anti-MMTV antibodies derived monoclonal antibodies. Normal peripheral blood lymphocytes (PBLs) were immunized in vitro in the presence of IL-2, with rabbit anti-B11 antibodies bound to silica beads. Following in vitro immunization, the lymphocytes were fused with the UC-792-6 human lymphoblastoid cell line. Four human hybridomas were found to secrete human monoclonal antibodies which bound to MMTV and HuMTV. Three of the secreted antibodies were of the IgG class and one of the IgM class. The specificity of binding was confirmed by direct and competitive ELISA assays and by radioimmunoprecipitation. Our study demonstrates the ability to generate human monoclonal anti-viral antibodies by in vitro immunization, employing "internal image" anti-idiotypic antibodies. The method can be used to generate human antibodies, especially against pathogenic agents or ill-defined antigens.

Antibodies, Anti-Idiotypic↗
PubMed1991

Antinuclear autoantibodies in healthy nonpregnant and pregnant women and their offspring.

Antinuclear autoantibodies have previously been detected in sera of healthy women although less frequently than in sera of women with autoimmune disorders. The effect of pregnancy on antinuclear autoantibody production in healthy women is as yet debatable. We present four studies in which, by employing the ELISA method, we evaluated the presence of six antinuclear autoantibodies (anti-ds DNA, anti-ss DNA, anti-poly(I), anti-cardiolipin, anti-Sm, and anti-RNP) in the sera of more than 1,000 healthy pregnant and nonpregnant women, including 196 pairs of matched maternal and cord blood sera. In all four studies healthy pregnant women did not demonstrate significantly higher prevalence rates of various serum antinuclear autoantibodies as compared to healthy non-pregnant women. All detected autoantibodies were of the IgM isotype. In only one infant (born to a healthy seronegative mother) was an autoantibody (IgM anti-ss DNA) detected. This may indicate that in certain circumstances the fetus is capable of self-production of autoantibodies.

Adolescent↗
PubMed1991

Parasitic infection and autoimmunity.

The studies summarized in this paper indicate that parasitic infections can serve as a trigger factor of autoimmune reactivity by several mechanisms. The relationship between parasites and autoimmunity could be manifested by the presence of autoantibodies or T-cells with autoreactivity. In spite of the evidence that has accumulated, the specific association between infection and autoimmunity is still obscure. The reasons for tissue damage in parasitic diseases are controversial. Some believe it is the result of pathogenic autoantibodies or autoreactive T-cells. Others argue against the causative role of autoimmunity in the formation of tissue lesions. The parasite itself could be the cause of tissue destruction, thus releasing high amounts of self antigens which might stimulate the autoreactivity. There is now little doubt that some degree parasite/host cross-reactivity occurs, and definition of cross-reacting antigens and epitopes is now taking place. It seems likely that a combination of events could result in cross-reactivity including: parasites themselves have cross reactive molecules and altered self antigens by adsorbing of parasite material to surrounding host cells. The mechanisms involved in parasites autoimmunity are complex and numerous, requiring a rigorous experimental approach to rationalize each step and determine its clinical importance. The developed methods in immunochemistry, monoclonal antibodies and hybridoma technology, and recombinant DNA research not only facilitate this kind of approach but also allow optimism for a successful outcome.

Autoimmunity↗
PubMed1991

Presence of a 16/6 related human anti-DNA common idiotype (SA1) in the anticardiolipin antibodies of patients with primary antiphospholipid syndrome.

Patients with primary antiphospholipid syndrome (PAPS) have few or no autoantibodies, other than the antiphospholipid antibodies (aPL) that could be natural autoantibodies encoded by germline genes. Some of the autoantibodies marked by the human anti-DNA common idiotype 16/6 have been found to be encoded by unmutated germline genes. Hence, we tested the sera of 19 patients with PAPS for the presence of the 16/6 idiotype which has also been found to be expressed on antibodies that bind cardiolipin. For this we used an ELISA method with antiserum against the SA1 idiotype which recognizes the 16/6. Five of our patients had the idiotype in at least one serum. Among the patients there was one with a variant of PAPS with hemolytic anemia and an IgM antibody to phosphatidylcholine that is akin to the natural autoantibody of normal mice encoded by germline genes VH11 and VH12. Inhibition studies with ssDNA, dsDNA and cardiolipin revealed that all 3 antigens decreased the serum levels of the SA1 idiotype despite absence of detectable anti-DNA antibodies by other methods. Our findings suggest that within the B cell clones that produce aPL in patients with PAPS there are some that produce immunoglobulins bearing 16/6 related idiotypes. This could indicate that some of the aPL present in patients with PAPS derive from natural autoantibody producing cell clones.

Antibodies↗