Methods regarding enhanced T-cell receptor-mediated tumor necrosis factor superfamily mRNA expression in peripheral blood leukocytes in patients with crohn's disease

1. A method of determining whether a human having Crohn's disease is likely to respond to immunosuppressive therapy, comprising:

stimulating leukocytes with an anti-T-cell receptor antibody in vitro in a first sample that comprises leukocytes from the human;

after the stimulation, measuring the amount of an mRNA encoding a tumor necrosis factor superfamily member in the first sample;

exposing leukocytes in vitro in a second sample comprising leukocytes from the human to a control stimulus;

measuring the amount of the mRNA in the second sample after exposing; and

determining a ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample, wherein a ratio of at least about 1.7:1 indicates that the human is likely to respond to said immunosuppressive therapy.

2. The method of claim 1 , wherein at least one of the first and second samples comprises whole blood.

3. The method of claim 1 , wherein the control stimulus comprises a purified control immunoglobulin.

4. The method of claim 1 , wherein the therapy targets TNF-α activity.

5. The method of claim 4 , wherein the therapy comprises administration of infliximab.

6. The method of claim 1 , wherein the therapy comprises administration of an agent selected from the group consisting of cyclosporine A and tacrolimus.

7. A method of evaluating the state of Crohn's disease in a human, comprising:

stimulating leukocytes with an anti-T-cell receptor antibody in vitro in a first sample that comprises leukocytes and is obtained at a first time from the human;

after the stimulation, measuring the amount of an mRNA encoding a tumor necrosis factor superfamily member in the first sample;

exposing leukocytes in vitro to a control stimulus in a second sample comprising leukocytes obtained from the human at the first time;

measuring the amount of the mRNA in the second sample after exposing;

determining a first ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample;

stimulating leukocytes with an anti-T-cell receptor antibody in vitro in a third sample that comprises leukocytes and is obtained from the human at a second time that is subsequent to the first time;

after the stimulation, measuring the amount of the mRNA in the third sample;

exposing leukocytes in vitro to a control stimulus in a fourth sample comprising leukocytes obtained from the human at the second time;

measuring the amount of the mRNA in the fourth sample after exposing;

determining a second ratio of the amount of the mRNA in the third sample to the amount of the mRNA in the fourth sample; and

comparing the first and second ratios, wherein a statistically significant difference in the first and second ratios is indicative of a change in the disease state.

8. The method of claim 7 , wherein the control stimulus comprises a purified control immunoglobulin.

9. The method of claim 7 , wherein at least one of the first, second, third and fourth samples comprises whole blood.

10. The method of claim 7 , wherein the significant difference in the ratios is that the second ratio is greater than the first ratio, and the change in disease state is a progression of the disease.

11. The method of claim 7 , wherein the significant difference in the ratios is that the first ratio is greater than the second ratio, and the change in disease state is a regression of the disease.

12. The method of any of claims 1 and 7 wherein the tumor necrosis factor superfamily (“TNFSF”) member is selected from the group consisting of TNFSF-2, TNFSF-5, TNFSF-6, and TNFSF-14.

13. The method of claim 12 , wherein the TNFSF member is selected from the group consisting of TNFSF-2 and TNFSF-14.