The immune tolerance network and rheumatic disease: Immune tolerance comes to the clinic

Diamond, Betty; Bluestone, Jeffrey A.; Wofsy, David

doi:10.1002/1529-0131(200108)44:8<1730::aid-art307>3.0.co;2-2

Cited by 15 publications

(3 citation statements)

References 60 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…66 Based on these experiences, an open-label pilot trial of CTLA4-IgG4m in combination with cyclophosphamide in patients with SLE nephritis is underway. 67,68 Inhibiting costimulatory molecule CD40:CD40 ligand (CD 154) interaction with BG9588 and IDEC 131…”

Section: Inhibiting Costimulatory Molecule Cd28:b7 Interaction With Amentioning

confidence: 99%

B lymphocytes and lupus nephritis: New insights into pathogenesis and targeted therapies

Bhat

Radhakrishnan

2008

Kidney International

View full text Add to dashboard Cite

Lupus nephritis (LN) in systemic lupus erythematosus (SLE) remains a major cause of morbidity and end-stage renal disease. While therapies such as corticosteroids, cyclophosphamide, and mycophenolate mofetil have improved outcomes, a significant proportion of patients have refractory disease or are unable to tolerate these agents. Limitations in existing therapies, along with advances in our understanding of the immunopathogenesis of SLE, have resulted in the development of new immunosuppressive and immunomodulatory treatments for SLE/LN. Dysfunction of the B lymphocyte-an important component of adaptive immunity-is thought to be important in the pathogenesis of SLE/LN. The goal of this study is to review our current understanding of the role of B cells in the pathogenesis of SLE, and to discuss new and emerging therapies that selectively target B cells in patients with SLE/LN. Novel strategies discussed include B-cell depletion by the monoclonal antibodies to B-cell markers, rituximab and epratuzumab; 'pharmapheresis' of pathogenic antibodies to dsDNA, by abetimus; blockade of T-cell costimulation of B cells by abatacept, belatacept, BG9588, and IDEC-131; and blockade of B-cell stimulation by belimumab. Preliminary results are promising, but in the absence of large controlled trials, caution must be exercised prior to the widespread use and acceptance of these treatments.

show abstract

Section: Inhibiting Costimulatory Molecule Cd28:b7 Interaction With Amentioning

confidence: 99%

B lymphocytes and lupus nephritis: New insights into pathogenesis and targeted therapies

Bhat

Radhakrishnan

2008

Kidney International

View full text Add to dashboard Cite

show abstract

“…Notably, the potential that blocking both CD28 and CD40 interactions in combination will be efficacious is under consideration and is a stated goal of the United States' National Institutes of Health-sponsored Immune Tolerance Network [56].…”

Section: Costimulationmentioning

confidence: 99%

Treatment of glomerulonephritis: Will we ever have options other than steroids and cytotoxics?

Javaid

Quigg

2005

Kidney International

View full text Add to dashboard Cite

Glomerulonephritis refers to a collection of primary renal disorders and those secondary to a systemic disease, all characterized by inflammation within the glomerulus. Given the underlying immunologic nature of these disorders, they are routinely treated with corticosteriods and various cytotoxic agents. Although in many instances such therapies are successful, they are associated with significant morbidity; as such, alternatives are clearly necessary. Our understanding of the pathogenesis of immunologic glomerular diseases has grown remarkably, in large part from the study of rodent disease models. Fundamental to each disorder is the development of an antigen-specific immune response followed by the effector stage of inflammation. To block the immune response, antigen-specific therapy can be used to induce tolerance, such as through the use of double-stranded DNA molecules in lupus nephritis. Since other antigen systems are less well characterized, inducing a more generalized impairment in the immune response by blocking costimulatory molecules CD40-CD154 and CD28-CD80/86 is a growing approach to treat various immunologic disorders and transplantation. To reduce glomerular inflammation, a variety of effector systems have been targeted, including complement, cytokines/chemokines, adhesion molecules, and mediators of cellular proliferation. Of these, antibodies targeting C5 in the complement system, and antibody and receptor antagonists of tumor necrosis factor-alpha (TNF-alpha) have already been used in glomerular disorders with some promise. Less specific blockade of receptor-mediated events stimulated by platelet-derived growth factors and cell cycle proteins may soon be applied to glomerulonephritis. Finally, interruption of fibrosing pathways, which lead to glomerulosclerosis and interstitial fibrosis common to the end-stage of all glomerulonephritis, is the subject of intense effort which may yield effective biologic therapies. In spite of all these advances, we still are dependent on steroids and cytotoxics to treat glomerulonephritis. To get past this, we must devote significant resources to take observations made in basic research laboratories to develop therapeutics and prove their utility in human disease.

show abstract

“…L'utilisation future de ces anticorps est envisageable à condition de bien comprendre le mécanisme d'autoimmunisation dépendant de B7-1 et 7-2 [6].…”

Section: Des Anticorps Monoclonaux Anti-b7 Et Anti-cd28unclassified

Immunothérapies du lupus systémique : innovations et perspectives

Sibilia¹,

Sordet²

2005

Revue du Rhumatisme

View full text Add to dashboard Cite

The immune tolerance network and rheumatic disease: Immune tolerance comes to the clinic

Cited by 15 publications

References 60 publications

B lymphocytes and lupus nephritis: New insights into pathogenesis and targeted therapies

B lymphocytes and lupus nephritis: New insights into pathogenesis and targeted therapies

Treatment of glomerulonephritis: Will we ever have options other than steroids and cytotoxics?

Immunothérapies du lupus systémique : innovations et perspectives

Contact Info

Product

Resources

About