Diagnosis and treatment of autoimmune diseases

1. A method of identifying and treating a patient having an autoimmune disease, the method comprising:

(i) providing a biological sample of a human subject suspected of having an autoimmune disease; wherein the biological sample is a blood sample, a serum sample, or a plasma sample;

(ii) measuring a level of cleaved high molecular weight kininogen (HMWK) in the biological sample;

(iii) identifying the human subject as having the autoimmune disease if the level of cleaved HMWK in the biological sample is elevated as compared to a control sample; and

(iv) treating the human subject identified in step (iii) with a plasma kallikrein inhibitor, an anti-inflammatory agent, or a combination thereof;

wherein the autoimmune disease is rheumatoid arthritis, Crohn's disease or ulcerative colitis.

2. A method of assessing development of and treating an autoimmune disease in a human subject, the method comprising:

(i) providing a first biological sample of a human subject who has an autoimmune disease at a first time point and a second biological sample of the subject at a second time point subsequent to the first point;

(ii) measuring a first level of cleaved high molecular weight kininogen (HMWK) in the first biological sample, and measuring a second level of cleaved HMWK in the second biological sample;

(iii) assessing development of the autoimmune disease in the human subject based on the change of the levels of cleaved HMWK in the first and second biological samples, wherein the second level of cleaved HMWK higher than the first level of cleaved HMWK indicates that the autoimmune disease progresses in the subject; and

(iv) treating the subject whose autoimmune disease progresses as determined in step (iii) with a plasma kallikrein inhibitor, an anti-inflammatory agent, or a combination thereof;

wherein the autoimmune disease is rheumatoid arthritis, Crohn's disease or ulcerative colitis, and wherein the first biological samples, the second biological samples, or both are blood samples, serum samples, or plasma samples.

3. A method of assessing the efficacy of a treatment in a human patient having an autoimmune disease, the method comprising:

(i) providing multiple biological samples of a human patient having an autoimmune disease and is subject to a treatment for the autoimmune disease, wherein the multiple biological samples are collected from the human patient during the course of the treatment; and wherein the multiple biological samples are blood samples, serum samples, or plasma samples;

(ii) measuring the levels of cleaved high molecular weight kininogen (HMWK) in the multiple biological samples;

(iii) assessing efficacy of the treatment based on the change of the levels of cleaved HMWK over the course of the treatment, wherein if the level of cleaved HMWK decreases during the course of the treatment, it indicates that the treatment is effective in the patient; and

(iv) changing conditions of the treatment or switching to a different treatment if the treatment is determined as ineffective in step (iii), wherein the different treatment comprises a plasma kallikrein inhibitor, an anti-inflammatory agent, or a combination thereof.

4. The method of claim 1 , wherein the biological sample comprises one or more protease inhibitors, which are added to the biological sample after collection.

5. The method of claim 1 , wherein the level of cleaved HMWK is measured by an assay that involves a binding agent specific to cleaved HMWK.

6. The method of claim 5 , wherein the binding agent is an antibody.

7. The method of claim 2 , wherein the first biological sample, the second biological sample, or both comprises one or more protease inhibitors, which are added to the biological sample(s) after its collection.

8. The method of claim 2 , wherein the first or second level of cleaved HMWK is measured by an assay that involves a binding agent specific to cleaved HMWK.

9. The method of claim 8 , wherein the binding agent is an antibody.

10. The method of claim 8 , wherein the assay is an enzyme-linked immunosorbent assay (ELISA) or an immunoblotting assay.

11. The method of claim 8 , wherein the assay is a Westernblotting assay involving an image detection system.

12. The method of claim 3 , wherein at least one of the multiple biological sample comprises one or more protease inhibitors, which are added to the sample after its collection.

13. The method of claim 3 , wherein the levels of cleaved HMWK in the multiple biological samples are measured by an assay that involves a binding agent specific to cleaved HMWK.

14. The method of claim 13 , wherein the binding agent is an antibody.

15. The method of claim 13 , wherein the assay is an enzyme-linked immunosorbent assay (ELISA) or an immunoblotting assay.

16. The method of claim 13 , wherein the assay is a Westernblotting assay involving an image detection system.

17. The method of claim 6 , wherein the assay is an enzyme-linked immunosorbent assay (ELISA) or an immunoblotting assay.

18. The method of claim 17 , wherein the assay is a Westernblotting assay involving an image detection system.