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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 631 records · Page 35Linked to original sources
PubMed1990

Pathogenic idiotypes of autoantibodies in autoimmunity: lessons from new experimental models of SLE.

Systemic lupus erythematosus (SLE) is considered a classical autoimmune disease that involves many biological systems. Similar to other autoimmune conditions, its etiology is multifactorial entailing genetic, environmental, hormonal, and immunologic factors. In this review we demonstrate that by using a pathogenic idiotype of anti-DNA autoantibodies, it is possible to explain some of the pathogenesis and diversity of clinical and serological manifestations reported by SLE patients. The 16/6 idiotype (Id) is a representative pathogenic idiotype of anti-DNA autoantibodies. The serum titers of 16/6 Id in SLE patients correlate with clinical activity of the disease, and are deposited in afflicted tissues in SLE patients. SLE was experimentally induced in naive mice after immunization with 1 microgram of the Id. The disease is characterized clinically (proteinuria), serologically (e.g., anti-dsDNA, anti-Sm antibodies), and by pathological findings (e.g., deposition of 16/6 Id in the kidneys). The condition can be induced by other human and mouse antibodies carrying the 16/6 Id, as well as by mouse antimonoclonal-16/6 Id and by T cell lines and clones specifically reactive with 16/6 Id. There are strain-dependent differences in susceptibility to the induction of systemic lupus erythematosus (SLE). Induction of SLE is directly correlated with the ability to respond to the 16/6 idiotype (or 16/6 Id)2 by anti-Id antibody production. It is easier to induce the disease in females, and it can be modulated by manipulation of sex hormones. Being able to identify the pathogenic idiotype allowed us to generate T suppressor (Ts) cells specific for the 16/6 Id. Treatment of mice with these T cells abrogated the disease. Our studies point to the importance of pathogenic idiotypes of autoantibodies in autoimmunity, which suggests that SLE may represent a dysregulation of a functional network of idiotypes-anti-idiotypes interactions among autoreactive B cells, T helper cells, and T suppressor cells.

Animals↗
PubMed1990

Anti-DNA idiotype- and anti-idiotype-specific T cell responses in patients with systemic lupus erythematosus and their first-degree relatives.

We examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE), their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a murine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.

Antibodies, Anti-Idiotypic↗
PubMed1990

The effect of the immunomodulator agent AS101 on interleukin-2 production in systemic lupus erythematosus (SLE) induced in mice by a pathogenic anti-DNA antibody.

The role of the synthetic immunomodulator AS101 on the production of interleukin-2 (IL-2) by spleen cells of mice with SLE was investigated. BALB/c female mice, in which SLE was induced by immunization with the pathogenic idiotype of anti-DNA antibody 16/6 Id were treated with AS101 for 7 weeks 2 and 4 months after induction of the disease. The ability of the splenocytes of the mice with SLE to produce IL-2 was restored after administration of AS101. This effect was particularly impressive when the 7-week AS101 treatment was initiated 4 months after immunization. Despite its beneficial effect on IL-2 production, AS101 exerted no influence on the titres of autoantibodies in the sera of the mice. It also had no effect on clinical parameters of SLE, such as the increased sedimentation rate, proteinuria and low white blood cell counts. Our data indicate that defective IL-2 production in SLE is probably secondary to other disease processes and is not necessarily associated with the production of autoantibodies in this disorder.

Adjuvants, Immunologic↗
PubMed1990

The importance of the pathogenic 16/6 idiotype in the induction of SLE in naive mice.

We have previously demonstrated the pathogenicity of the common anti-DNA idiotype designated 16/6 Id. Immunization of naive mice with the 16/6 Id induced SLE-like disease characterized by serological (e.g. anti-dsDNA and anti-Sm auto-antibodies), clinical (increased ESR, leucopenia and proteinuria), and pathological (16/6 Id deposition in kidneys) parameters. To elucidate further the role of the 16/6 Id in SLE induction the following studies were carried out: BALB/c mice were immunized with SA-1, a human anti-DNA monoclonal antibody carrying the 16/6 Id; TB-68, a mouse monoclonal anti-tuberculosis (TB) glycolipid, which binds dsDNA and carries the 16/6 Id; TB-72, a mouse monoclonal anti-TB glycolipid that binds DNA and does not harbour the 16/6 Id; and 4B4, a human anti-Sm antibody that carries the 16/6 Id. SLE was induced in BALB/c mice only when immunized with SA-1, TB-68, and 4B4, namely antibodies with diverse binding capacities albeit having the 16/6 Id. Our studies further support previous evidence on the pathogenic role attributed to the 16/6 Id in SLE, and suggest that SLE is most probably an idiotype-induced disease.

Animals↗
PubMed1990

Antinuclear autoantibodies in sera of patients with IgA nephropathy.

IgA nephropathy (IgAN), assumed to be a chronic immune complex glomerulonephritis, has been sometimes associated with various autoimmune diseases and autoimmune phenomena including autoantibody production. The current study was aimed at thoroughly investigating the frequency of raised autoantibody titers against five common nuclear autoantigens in a large number of patients with IgAN as well as patients with other primary immune complex glomerulopathies and normal controls. The incidence of autoantibodies (greater than 2 SD less than 3 SD of controls) in the IgAN group ranged between 13% in the case of anticardiolipin antibodies, and 19% in the case of antiribonucleoprotein antibodies, yet was not found to be significantly different from the incidence observed in the other control groups. In none of the subjects a titer above 3 SD of the means of controls was found. Our study clearly points to the fact that IgAN, while being an immune-mediated disease, is not a clear-cut autoimmune condition. The finding of autoantibodies in these patients may be merely incidental.

Antibodies, Antinuclear↗
PubMed1990

Disease specificity of antibodies to poly (ADP-ribose); their relationships to anti-DNA antibodies and to disease activity in lupus.

In this study we have measured the level of anti poly (ADP-ribose) antibodies in the sera of a number of patients with SLE and their relatives, patients with a wide variety of other autoimmune and infectious diseases, and a group of normal healthy controls. It was found that these antibodies were not disease specific but were present in nine out of thirteen groups tested in significant numbers. The levels of anti poly (ADP-ribose) antibodies and anti DNA antibodies in SLE patients bled serially were also measured. The level of these antibodies fluctuated in parallel in many of these patients, although the anti poly (ADP-ribose) antibodies reflected disease activity more accurately in some.

Antibodies, Antinuclear↗
PubMed1990

Characteristics of antineuronal antibodies in systemic lupus erythematosus patients with and without central nervous system involvement: the role of mycobacterial cross-reacting antigens.

Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.

Adult↗
PubMed1990

The genetic regulation of the induction of experimental SLE.

We have recently reported the induction of systemic lupus erythematosus (SLE) in C3H.SW female mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype termed 16/6 Id. In the present study, the ability to induce experimental SLE in seven inbred mouse strains by immunization with the 16/6 Id was examined. Two out of the seven strains failed to develop the disease. These two strains did not produce antibodies specific to the 16/6 Id, while the other five strains produced high titres of anti-16/6 Id antibodies. The anti-16/6 Id antibody response, followed by the induction of the disease, was not found to be MHC or Ig heavy chain allotype linked. F1 hybrids between a resistant strain and two of the susceptible strains were found to be resistant to the induction of the disease, indicating that susceptibility is inherited as a recessive trait. In the autoimmune NZB/W F1 female mice, immunization with the 16/6 Id resulted in an early onset of the SLE-like disease. The results of the present study indicate the role of the anti-16/6 Id antibodies in the induction of experimental SLE, and provide direct evidence for the importance of the genetic background in determining susceptibility to SLE.

Animals↗
PubMed1990

Sex hormone involvement in the induction of experimental systemic lupus erythematosus by a pathogenic anti-DNA idiotype in naive mice.

The effect of sex hormones on the induction of experimental systemic lupus erythematosus (SLE) with a human anti-DNA (16/6 Id +) antibody, was studied. We found that injection of the pathogenic idiotype to BALB/c females and orchiectomized males treated with estrogen caused a rapid outburst of the disease 3 months after immunization, while nonestrogen treated mice developed the disease 5 months after immunization. The flare of SLE disease was characterized by raised levels of autoantibodies in the sera to dsDNA, histones, cardiolipin, Sm, RNP, SSA (Ro), SSB (La) and an emergence of high titers of mouse antibody carrying the 16/6 Id. These enhanced antibody levels were associated with an increase in erythrocyte sedimentation rate, proteinuria and leukopenia. Immunofluorescent studies confirmed the existence of immune complexes in the afflicted kidneys. Testosterone treated BALB/c females and orchiectomized males developed a classical response to the human anti-DNA antibody (16/6 Id +), but failed to develop fulminant SLE-like disease. Our data demonstrate the importance of sex hormones on the induction of experimental SLE-like disease in mice with no genetic tendency to autoimmunity.

Animals↗
PubMed1989

[Tuberculosis in a general hospital 1987].

Tuberculosis (TB) was diagnosed in 15 patients admitted during a 1-year period starting November 1986. 4 had been treated with corticosteroids prior to diagnosis. Most were admitted with exacerbation of chronic obstructive pulmonary disease, acute respiratory failure and prolonged fever. The most frequent X-ray findings were infiltrates in the lower lobes and the middle lobe. Sputum cultures were positive for TB in only 4 patients, while culture of gastric aspirates was diagnostic in 9. Our findings point to an increase in the detection of TB in the Negev. It must be ruled out in patients with diabetes, those undergoing prolonged corticosteroid therapy and in Bedouin and Yemenite patients in whom there is a greater incidence of the disease. Culture of gastric aspirates should be included in the workup for TB.

Hospitals, General↗