Method for diagnosing auto-immune chronic urticaria

1. A method for diagnosing auto-immune chronic urticaria in a patient, the method comprising:

reacting a serum sample from the patient with donor basophils and associated leukocytes obtained from an individual donor;

measuring histamine released by the donor basophils and associated leukocytes in response to the patient serum;

using the measured histamine released to calculate a CU index score, wherein the CU index is represented by the following formula:

(α/β)=CU Index,

wherein α is the amount of histamine released by the donor basophils and associated leukocytes in response to the patient serum, and β is a normalized baseline of histamine release,

wherein the normalized baseline of histamine release is a mean percentage plus 1 or more standard deviations thereof of histamine released by the donor basophils and associated leukocytes following challenges with control sera obtained from serum donors that do not exhibit clinical symptoms of chronic urticaria;

wherein the CU index score is an indicator of a diagnosis of auto-immune chronic urticaria in the patient; and

providing information to a physician to facilitate diagnosis of auto-immune chronic urticaria in the patient based on the CU index score.

2. The method of claim 1 , wherein the diagnosis is positive for autoimmune chronic urticaria when the CU index score is 1 or more.

3. The method of claim 1 , wherein the CU index is multiplied by 10 to provide the CU index score.

4. The method of claim 3 , wherein the diagnosis is positive for autoimmune chronic urticaria when the CU index score is 10 or more.

5. The method of claim 1 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

6. The method of claim 3 , wherein said measuring is by Histamine Enzyme-Linked Immunoassay (ELISA).

7. The method of claim 1 , wherein a CU index score of 1 or more indicates that the patient should be treated with an immune modulating drug.

8. The method of claim 3 , wherein a CU index score of 10 or more indicates that the patient should be treated with an immune modulating drug.

9. The method of claim 1 , wherein the normalized baseline of histamine release is a mean percentage plus 2 or more standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

10. The method of claim 3 , wherein the normalized baseline of histamine release is a mean percentage plus about 2 standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

11. A method for determining severity of auto-immune chronic urticaria in a patient, the method comprising:

reacting a serum sample from the patient with donor basophils and associated leukocytes obtained from an individual donor;

measuring histamine released by the donor basophils and associated leukocytes in response to the patient serum;

using the measured histamine released to calculate a CU index score, wherein the CU index is represented by the following formula:

(α/β)=CU Index,

wherein α is the amount of histamine released by the donor basophils and associated leukocytes in response to the patient serum, and β is a normalized baseline of histamine release, wherein the normalized baseline of histamine release is a mean percentage plus 1 or more standard deviations thereof of histamine released by the donor basophils and associated leukocytes following challenges with control sera obtained from serum donors that do not exhibit clinical symptoms of chronic urticaria;

wherein a CU index score of 1 or more indicates positive diagnosis for autoimmune chronic urticaria; and

providing information to a physician to facilitate diagnosis of the severity of auto-immune chronic urticaria in the patient based on the CU index score.

12. The method of claim 11 , wherein the CU index is multiplied by 10 to provide the CU index score and a CU index score of 10 or more indicates a positive diagnosis of chronic urticaria in the patient.

13. The method of claim 11 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

14. The method of claim 12 , wherein said measuring is by Histamine Enzyme-Linked Immunoassay (ELISA).

15. The method of claim 11 , wherein a CU index score of 1 or more indicates that the patient should be treated with an immune modulating drug.

16. The method of claim 12 , wherein a CU index score of 10 or more indicates that the patient should be treated with an immune modulating drug.

17. The method of claim 11 , wherein the normalized baseline of histamine release is a mean percentage plus 2 or more standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

18. The method of claim 12 , wherein the normalized baseline of histamine release is a mean percentage plus about 2 standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

19. A method for determining whether a patient should be treated with an immune-modulating drug for treatment of auto-immune chronic urticaria, the method comprising:

reacting a serum sample from the patient with donor basophils and associated leukocytes obtained from an individual donor;

measuring histamine released by the donor basophils and associated leukocytes in response to the patient serum;

using the measured histamine released to calculate a CU index score, wherein the CU index is represented by the following formula:

(α/β)=CU Index,

wherein α is the amount of histamine released by the donor basophils and associated leukocytes in response to the patient serum, and β is a normalized baseline of histamine release, wherein the normalized baseline of histamine release is a mean percentage plus 1 or more standard deviations thereof of histamine released by the donor basophils and associated leukocytes following challenges with control sera obtained from serum donors that do not exhibit clinical symptoms of chronic urticaria;

wherein a CU index score of 1 or more indicates a positive diagnosis for autoimmune chronic urticaria in the patient; and

providing information to a physician to facilitate a determination of whether the patient should be treated with an immune-modulating drug for treatment auto-immune chronic urticaria based on the CU index score.

20. The method of claim 19 , wherein the CU index is multiplied by 10 to provide the CU index score and a CU index score of 10 or more indicates a positive diagnosis of chronic urticaria in the patient.

21. The method of claim 19 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

22. The method of claim 20 , wherein said measuring is by Histamine Enzyme-Linked Immunoassay (ELISA).

23. The method of claim 19 , wherein the normalized baseline of histamine release is a mean percentage plus 2 or more standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

24. The method of claim 20 , wherein the normalized baseline of histamine release is a mean percentage plus about 2 standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

25. A method for monitoring efficacy of an immune modulating drug in treatment of auto-immune chronic urticaria in a patient to whom the immune modulating drug was administered, the method comprising:

reacting a serum sample from the patient with donor basophils and associated leukocytes obtained from an individual donor;

measuring histamine released by the donor basophils and associated leukocytes in response to the patient serum; and

using the measured histamine released to calculate a CU index score, wherein the CU index is represented by the following formula:

(α/β)=CU Index,

wherein α is the amount of histamine released by the donor basophils and associated leukocytes in response to the patient serum, and β is a normalized baseline of histamine release, wherein the normalized baseline of histamine release is a mean percentage plus 1 or more standard deviations thereof of histamine released by the donor basophils and associated leukocytes following challenges with control sera obtained from serum donors that do not exhibit clinical symptoms of chronic urticaria;

wherein a CU index score of 1 or more indicates a positive diagnosis for autoimmune chronic urticaria in the patient and the CU index score is an indicator of efficacy of the immune modulating drug in treating autoimmune chronic urticaria in the patient; and

providing information to a physician as to the efficacy of the immune modulating drug in treatment of chronic urticaria in the patient based on the CU index score.

26. The method of claim 25 , wherein the CU index multiplied by 10 to provide the CU index score and a CU index score of 10 or more indicates a positive diagnosis of chronic urticaria in the patient.

27. The method of claim 25 , wherein the normalized baseline of histamine release is a mean percentage plus 2 or more standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

28. The method of claim 26 , wherein the normalized baseline of histamine release is a mean percentage plus about 2 standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

29. The method of claim 25 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

30. The method of claim 26 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

31. A method for determining whether a subject should be included in a clinical trial of a candidate drug for treatment of chronic urticaria, the method comprising:

reacting a serum sample from the patient with donor basophils and associated leukocytes obtained from an individual donor;

measuring histamine released by the donor basophils and associated leukocytes in response to the patient serum; and

using the measured histamine released to calculate a CU index score, wherein the CU index is represented by the following formula:

(α/β)=CU Index,

wherein α is the amount of histamine released by the donor basophils and associated leukocytes in response to the patient serum, and β is a normalized baseline of histamine release, wherein the normalized baseline of histamine release is a mean percentage plus 1 or more standard deviations thereof of histamine released by the donor basophils and associated leukocytes following challenges with control sera obtained from serum donors that do not exhibit clinical symptoms of chronic urticaria;

wherein a CU index score of 1 or more indicates a positive diagnosis for autoimmune chronic urticaria in the patient; and

providing information as to whether the patient should be included in a clinical trial for immune modulating drugs based on the CU index score.

32. The method of claim 31 , wherein the CU index multiplied by 10 to provide the CU index score and a CU index score of 10 or more indicates a positive diagnosis of chronic urticaria in the patient.

33. The method of claim 31 , wherein the normalized baseline of histamine release is a mean percentage plus 2 or more standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

34. The method of claim 32 , wherein the normalized baseline of histamine release is a mean percentage plus about 2 standard deviations of histamine released by donor basophils and associated leukocytes of an individual donor following challenge with a control serum obtained from one or more donors that do not exhibit clinical symptoms of chronic urticaria.

35. The method of claim 31 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).

36. The method of claim 32 , wherein said measuring is by histamine Enzyme-Linked Immunoassay (ELISA).