Use of anti-gp 39 antibodies for treatment and/or reversal of lupus and associated kidney disease
A technology for antibodies and lupus, applied in the field of soluble ligands and fusion molecules, can solve problems such as manifestations
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[0047] (iii) Preparation of purified CD40CR;
[0048] (iv) use of a ligand that binds CD40CR; and
[0049] (v) Use of CD40CR.
[0050] (Ⅲ) Preparation of purified CD40CR; (especially for the treatment of progressive lupus, such as systemic lupus erythematosus or drug-induced lupus).
[0051] The present invention provides soluble ligands of CD40CR, including (i) a fusion molecule containing at least a part of CD40 protein and (ii) an antibody or antibody fragment specifically binding to CD40CR, or gp39, or CD154 known as the antigen.
[0052] The term "soluble", as used herein, means that the ligands of the invention are not always bound to the plasma membrane of the cell. However, the soluble ligands of the invention can be immobilized on acellular solid supports, including lipid, protein, or carbohydrate molecules, beads, vesicles, magnetic particles, fibers, etc., or can be embedded in implants or in vesicles.
[0053] The ability of such a ligand to bind CD40CR can be ...
Embodiment 1
[0106] Example 1 Novel receptor CD40CR on activated helper T cells binds to CD40 and transduces B cell-associated activation signals Materials and methods
[0107] animal
[0108] Female DBA / 2J mice (Jackson Laboratories, Bar Harbor, ME) were used to prepare filler cells to support T h Clones were grown and used to generate resting B cells.
[0109] D1.6 is a type I-A d -Restricted rabbit immunoglobulin-specific T h 1 clone (Kurt-Jones et al., J. Exp. Med., 166:1774-1787 (1987)) obtained from Dr. David Parker (University of Massachusetts, Worcester). D1.6 is referred to herein as T h 1.
[0110] T h 1(8×10 6 per well) were cultured in clustered wells (6-well plate, Coming, NY), each well of which had been coated with anti-D3 40 μg / 4 ml PBS for 16 hours.
[0111] Cell plasma membranes were prepared by settling down a discontinuous sucrose gradient as described by Noelle et al. (supra).
[0112] Resting splenic B cells were prepared by sedimen...
Embodiment 2
[0138] Use of anti-gp39 antibody for treating or preventing lupus
[0139] Systemic lupus erythematosus (SLE) is a disease characterized by the production of multiple pathogenic autoantibodies (Boumpas, Ann Int Med, 1995). These antibodies cause damage either directly through recognition of antigenic determinants on normal cells or indirectly through the formation of immune complexes that can deposit in normal tissues and activate the complement cascade.
[0140] As with normal antibody responses, it is now clear from studies of SLE and lupus-like diseases in inbred mouse strains that the production of lupus B cell autoantibodies is dependent on CD4 + Auxiliary T(T h ) Cell synergy. The examples come from studies of a traditional mouse model of SLE, the female offspring of NZB / NZW that resembles human SLE in many respects, including autoantibody production and development of immune complex glomerulonephritis. Treatment of mice with reduced anti-CD4 antibodies prevente...
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