Methods of treating glomerulonephritis associated with IGA nephropathy for TACI-immunoglobulin fusion proteins
Molecules that interfere with the binding of a tumor necrosis factor receptor with its ligand, such as a soluble receptor, have proven usefulness in both basic research and as therapeutics. The present invention provides improved soluble transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) receptors.
1. A method of treating glomerulonephritis associated with IgA nephropathy comprising administering to a mammalian subject in need thereof a composition comprising a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)—immunoglobulin fusion protein, wherein the TACI-immunoglobulin fusion protein comprises:
(a) a TACI receptor moiety that consists of:
i) amino acid residues 30-110 of SEQ ID NO:2; or,
ii) amino acid residues 30-154 of SEQ ID NO:2;
wherein the TACI receptor moiety binds at least one of ZTNF2 or ZTNF4, and
(b) an immunoglobulin moiety comprising a C H2 and C H3 domain.
2. The method of claim 1 , wherein the immunoglobulin moiety is an IgG1 immunoglobulin moiety.
3. The method of claim 2 , wherein the immunoglobulin moiety is an IgG1 Fc fragment that comprises a disulfide linked heavy chain hinge region, a C H2 domain and a C H3 domain.
4. A method of treating glomerulonephritis associated with IgA nephropathy comprising administering to a mammalian subject in need thereof a composition comprising a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)—immunoglobulin fusion protein, wherein the TACI-immunoglobulin fusion protein comprises:
(a) a TACI receptor moiety that consists of:
i) amino acid residues 30-110 of SEQ ID NO:2; or,
ii) amino acid residues 30-154 of SEQ ID NO:2;
wherein the TACI receptor moiety binds at least one of ZTNF2 or ZTNF4, and
(b) an immunoglobulin moiety comprising a C H2 and C H3 domain,
wherein the TACI-immunoglobulin fusion protein has an amino acid sequence of SEQ ID NO:54.
5. A method of treating glomerulonephritis associated with IgA nephropathy comprising administering to a mammalian subject in need thereof a composition comprising a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)—immunoglobulin fusion protein, wherein the TACI-immunoglobulin fusion protein comprises:
(a) a TACI receptor moiety that consists of:
i) amino acid residues 30-110 of SEQ ID NO:2; or,
ii) amino acid residues 30-154 of SEQ ID NO:2;
wherein the TACI receptor moiety binds at least one of ZTNF2 or ZTNF4, and
(b) an immunoglobulin moiety comprising a C H2 and C H3 domain,
wherein the TACI-immunoglobulin fusion protein has an amino acid sequence comprising the secreted form of the amino acid sequence of SEQ ID NO:54.
6. The method of claim 5 , wherein the TACI-immunoglobulin fusion protein comprises the amino acid sequence of SEQ ID NO:54, wherein the optimized tPA (otPA) leader sequence (SEQ ID NO:25) has been removed.
7. The method of claim 1 , wherein the TACI-immunoglobulin fusion protein is a dimer.
8. The method of claim 1 , wherein said subject is a human.
9. The method of claim 4 , wherein said subject is a human.
10. The method of claim 5 , wherein said subject is a human.