<i>In vivo</i>
            therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor

Waldor, Matthew K.; Subramaniam, Sriram; McDevitt, Hugh O.; Steinman, Lawrence

doi:10.1073/pnas.80.9.2713

Cited by 141 publications

(49 citation statements)

References 29 publications

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“…Indeed, of the Israeli group of MG patients we tested, 27% were determined to express jointly HLA-B8, DR3, a significantly higher percentage from that observed in the Israeli healthy control group. This observation is of special interest because many autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis in the Israeli population do not follow the reported HLA associations (22)(23)(24) (25)(26)(27). Class II HLA polymorphisms have been described in MG patients who are HLA-DR 3 (25).…”

Section: Resultsmentioning

confidence: 99%

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In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

Brocke¹,

Brautbar²,

Steinman³

et al. 1988

J. Clin. Invest.

120

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To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor a-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.

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Section: Resultsmentioning

confidence: 99%

“…Thus, polymorphism, linked to MG in the HLA-D region may map to HLA-DP or perhaps DX and DZ. In the mouse, responsiveness to AChR is controlled by the I-A : chain (26,27).…”

Section: Resultsmentioning

confidence: 99%

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

Brocke¹,

Brautbar²,

Steinman³

et al. 1988

J. Clin. Invest.

120

View full text Add to dashboard Cite

show abstract

“…Studies using animal models of induced or spontaneous autoimmune diseases generally show that production of pathogenic autoantibodies is a T cell-dependent process (9)(10)(11)(12)(13)(14)(15)(16). However, recent studies in models of lupus erythematosus demonstrated that the role of T cells is considerably more complex than previously believed and that, in certain experimental settings, B cells alone can drive systemic autoimmunity independently of T cells (17)(18)(19).…”

mentioning

confidence: 99%

T Cells Are Required for the Production of Blister-Inducing Autoantibodies in Experimental Epidermolysis Bullosa Acquisita

Sitaru

Sesărman

Mihai

et al. 2009

The Journal of Immunology

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Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addressed the role of T cells for the production of blister-inducing autoantibodies in mice immunized with type VII collagen. To detect autoreactive type VII collagen-specific T cells, lymph node cells from immunized SJL mice were stimulated in vitro with recombinant Ag, and their proliferation was measured by radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled cells. Interestingly, using synthetic peptides of the immunogen, partly different T and B cell epitopes in mice immunized with type VII collagen were demonstrated. In contrast to wild-type mice, immunization with type VII collagen of SJL athymic nude mice lacking T cells did not induce an autoimmune response and blistering phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild-type mice showed a robust and durable autoantibody production resulting in subepidermal blistering disease in the recipients. Our present results demonstrate that T cells are required for the initiation of autoimmunity against type VII collagen in experimental epidermolysis bullosa acquisita and provide a basis for developing T cell-directed immunomodulatory strategies for this and related autoimmune diseases.

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“…For example, treatment with anti-MHC class II monoclonal Abs (monoclonal Abs to the murine I-E equivalent) prevented thyroidal and pancreatic autoimmunity in BioBreeding/Worcester (BB/W) rats (Boitard et al, 1985). Treatment of anti-I-A monoclonal Abs ameliorated many autoimmune diseases in animal models including lupus nephritis (NZB/W F1) (Adelman et al, 1983), experimental autoimmune uveoretinitis (Rao et al, 1989), and experimental autoimmune myasthenia gravis (Waldor et al, 1983). Engineered antigen-presenting cells have also been used for immunomodulation and tolerance induction.…”

Section: Therapies Targeting Mhc Molecules or Antigen-presenting Cellmentioning

confidence: 99%

New Therapeutic Challenges in Autoimmune Diseases

Choi¹

2012

Autoimmune Diseases - Contributing Factors, Specific Cases of Autoimmune Diseases, and Stem Cell and Other Therapies

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In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor

Cited by 141 publications

References 29 publications

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

T Cells Are Required for the Production of Blister-Inducing Autoantibodies in Experimental Epidermolysis Bullosa Acquisita

New Therapeutic Challenges in Autoimmune Diseases

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