Autoimmunity: polyclonal activation or antigen induction?

Dziarski, Roman

doi:10.1016/0167-5699(88)91333-3

Cited by 93 publications

(37 citation statements)

References 52 publications

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“…The current study suggests that polyclonal activation of B cells and preferential activation ofautoantibody producing clones are not mutually exclusive; rather, both mechanisms may contribute to the formation of anti-DNA antibody in SLE patients. A similar combined model of autoimmunity was proposed recently by Dziarski and Klinman et al (57,58).…”

Section: Resultsmentioning

confidence: 93%

Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

Suzuki¹,

Sakane²,

Engleman³

1990

J. Clin. Invest.

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Although the presence of anti-DNA antibody is a hallmark of systemic lupus erythematosus (SLE), neither the subsets of B cells that secrete anti-DNA antibody nor the stimuli responsible for the induction of anti-DNA secretion is known. In particular, the role of CD5+ B cells in human SLE, a distinct subpopulation of antibody-secreting cells shown previously to be a source of anti-DNA antibody in murine models of SLE, is unknown. To approach these questions, we developed a sensitive enzyme-linked immunospot (ELIspot) assay to measure spontaneous secretion of antibody to single-stranded (ss) DNA, double-stranded (ds) DNA, tetanus toxoid, and polyclonal immunoglobulin (Ig) by purified CD5+ and CD5-B cells of 15 SLE patients and 15 healthy control subjects. The B cells of only 1 of 15 healthy subjects secreted a significant level of anti-ssDNA antibody, and none secreted anti-dsDNA. By contrast, in the majority of SLE patients both CD5+ and CD5-B cells secreted IgG and/or IgM anti-ssDNA as well as antidsDNA antibody. Further analysis of the anti-ssDNA response revealed that the level of IgG and IgM anti-DNA antibody secretion by CD5-B cells correlated closely with the level of polyclonal Ig ptoduction by the same subpopulation (r = 0.81 and 0.70, respectively). In contrast, production of anti-DNA by CD5+ B cells occurred independently of polyclonal Ig production by both CD5+ and CD5-B cell subpopulations. These results suggest that in human SLE there exist two anti-DNA antibody-producing B cell subpopulations with distinct induction mechanisms: one (CD5+), which independently secretes anti-DNA, and another (CD5-), which produces anti-DNA as an apparent consequence of polyclonal B cell activation. (J. Clin. Invest. 1990. 85:238-247.) anti-DNA antibody .

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Section: Resultsmentioning

confidence: 93%

Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

Suzuki¹,

Sakane²,

Engleman³

1990

J. Clin. Invest.

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“…Different mechanisms have been proposed to explain the development of non-organ specific autoantibodies. These include polyclonal B cell activation and (auto)antigen driven responses [10]. Several lines of evidence suggest that the latter mechanism is implicated in eliciting anti-Ro/SS-A and anti-La/SS-B antibodies.…”

Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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Autoimmune diseases such as Sjögren's Syndrome and systemic lupus erythematosus (SLE) are characterized by serum autoantibodies against protein components of small cytoplasmic ribonucleoproteins (scRNPs). The origin and regulation of these anti-Ro/SS-A and anti-La/SS-B antibodies is not well understood. Regular co-occurrence of these two autoantibodies in humans together with murine studies on antibody responses against scRNPs after immunization suggest a role for scRNPs as common antigen. We sought additional evidence for this hypothesis in a longitudinal serological study of patients with SLE. Quantitative measurement of the antibody responses against Ro/SS-A and La/SS-B proteins and for comparison to dsDNA in 852 serum samples was performed. These samples were collected from nine patients during an average observation period of more than 10 years. A significant and strong correlation between the two anti-scRNP responses emerged during 90% of follow-up. In contrast, correlation of anti-scRNP with anti-dsDNA responses was remarkably absent in the same patients. Our results confirm the unique relationship between anti-Ro/SS-A and anti-La/ SS-B responses and could thus be interpreted as support for a model wherein induction and perpetuation of autoantibody production is dependent on scRNPs containing both proteins as antigen.

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“…These anti-DNA antibodies resemble some anti-DNA antibodies expressed in spontaneous autoimmune disease in these mice [11]. Thus, bacteria can provide both polyclonal activators and cross-reacting antigens for the production of anti-DNA antibodies and thereby may play a role in the pathogenesis of systemic autoimmune disease [12,13]. The bacteria involved might originate from the intestinal tract, since it was found that the DNA component of circulating immune complexes of patients with SLE hybridized with the lacZ gene of Escherichia coli [14].…”

Section: Introductionmentioning

confidence: 80%

Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract

Apperloo-Renkema¹,

Bootsma

Mulder³

et al. 1995

Epidemiol. Infect.

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SUMMARYExperimental data suggest a role for the microflora in the disease expression of systemic lupus erythematosus (SLE). In active SLE anti-ds-DNA antibodies are supposed to be pathogenic by forming immune complexes with DNA. Bacteria might induce the production of anti-ds-DNA antibodies. To explore the relation between the host and his microflora in SLE in comparison with healthy controls we studied the prevalence of systemic antibodies to faecal bacteria that were discriminated by their morphology by indirect immunofluorescence.IgM titres against their own faecal microflora were found to be lower both in active and inactive SLE when compared to healthy individuals. IgG-class antibacterial antibodies were increased in inactive SLE but decreased in active SLE compared to inactive SLE and healthy controls, although plasma levels of total IgG were almost doubled in active SLE. The lower IgG antibacterial antibody titres in active SLE might possibly result from sequestration of these IgG antibodies in immune complexes, indicating a possible role for antibacterial antibodies in exacerbations of SLE.

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Autoimmunity: polyclonal activation or antigen induction?

Cited by 93 publications

References 52 publications

Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract

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