Methods of diagnosing and prognosing hodgkin's lymphoma
View Patent ↗The present invention relates to nucleic acid molecules encoding Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to antibodies or portions thereof that specifically bind Neutrokine-alpha and/or Neutrokine-alphaSV and diagnostic and therapeutic methods using these antibodies. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders using the compositions of the invention.
1. A method of detecting diagnosing Hodgkin's lymphoma comprising:
(a) contacting serum from a patient suspected of having Hodgkin's lymphoma with an agent that binds a soluble Neutrokine-α polypeptide consisting of the amino acid sequence from about amino acid 134 to about amino acid 285 of SEQ ID NO: 2;
(b) measuring the expression level of the soluble Neutrokine-α polypeptide in the serum; and
(c) comparing the measured expression level of the soluble Neutrokine-α polypeptide with a standard expression level of the soluble Neutrokine-α polypeptide that is less than 0.5 ng/ml,
wherein an increase in the expression level of the soluble Neutrokine-α polypeptide in the serum relative to the standard is indicative of Hodgkin's lymphoma, and wherein the agent is selected from the group consisting of:
(i) an anti-Neutrokine-α antibody; and
(ii) a Neutrokine-α receptor or a soluble Neutrokine-α receptor.
2. The method of claim 1 , wherein the Neutrokine-α receptor or soluble Neutrokine-α receptor is selected from the group consisting of:
(a) transmembrane activator and CAML interactor (TACI);
(b); B cell maturation antigen (BCMA); and
(c) BAFF-R.
3. The method of claim 1 , wherein measuring the expression level of the soluble Neutrokine-α polypeptide is performed using an assay selected from the group consisting of:
(a) ELISA;
(b) radioimmunoassay;
(c) in situ immunoassay;
(d) Western blot;
(e) agglutination assay; and
precipitation reactions.
4. The method of claim 1 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 2.0 ng/ml.
5. The method of claim 1 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 2.5 ng/ml.
6. The method of claim 1 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 3.0 ng/ml.
7. The method of claim 1 , wherein the Hodgkin's lymphoma is relapsed Hodgkin's lymphoma.
8. A method of prognosing Hodgkin's lymphoma comprising:
(a) contacting serum from a patient diagnosed with Hodgkin's lymphoma with an agent that binds a soluble Neutrokine-α polypeptide consisting of the amino acid sequence from about amino acid 134 to about amino acid 285 of SEQ ID NO: 2;
(b) measuring the expression level of the soluble Neutrokine-α polypeptide in the serum;
(c) measuring at least one additional indicator selected from the group consisting of:
(i) male gender;
(ii) stage 4 disease;
(iii) bulky disease >7.5 cm;
(iv) high LDH;
(v) high β2-microglobulin;
(vi) resistance to therapy; and
(vii) shorter failure free survival; and
(d) comparing the measured expression level of the soluble Neutrokine-α polypeptide with a standard expression level of soluble Neutrokine-α polypeptide that is less than 0.5 ng/ml,
wherein an increase in the expression level of the soluble Neutrokine-α polypeptide in the serum relative to the standard is indicative of Hodgkin's lymphoma; wherein the agent is selected from the group consisting of:
(i) an anti-Neutrokine-α antibody; and
(ii) a Neutrokine-α receptor or a soluble Neutrokine-α receptor; and
wherein having at least one additional indicator is indicative of a worse prognosis.
9. The method of claim 8 , wherein the Neutrokine-α receptor or soluble Neutrokine-α receptor is selected from the group consisting of:
(a) transmembrane activator and CAML interactor (TACI);
(b) B-cell maturation antigen (BCMA); and
(c) BAFF-R.
10. The method of claim 8 , wherein measuring the expression level of the soluble Neutrokine-α polypeptide is performed using an assay selected from the group consisting of:
(a) ELISA;
(b) radioimmunoassay;
(c) in situ immunoassay;
(d) Western blot;
(e) agglutination assay; and
(f) precipitation reactions.
11. The method of claim 8 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 2.0 ng/ml.
12. The method of claim 8 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 2.5 ng/ml.
13. The method of claim 8 , wherein the expression level of the soluble Neutrokine-α polypeptide in serum is greater than 3.0 ng/ml.