CXCR4 and ROBO1 expression as markers for autoimmune diabetes
CXCR4 and ROBO-1 are biomarkers associated with type 1 diabetes. Expression of CXCR4 and ROBO-1 in peripheral CD3 T cells is substantially higher in patients with autoimmune diabetes (type 1 diabetes) than in non-diabetic patients. Therapies are disclosed for reducing the progression of type 1 diabetes, and to reduce the risk of developing type 1 diabetes in patients who are at risk of developing type 1 diabetes.
1. A method for treating autoimmune diabetes in a vertebrate patient, said method comprising the steps of:
(a) assaying T cells from the patient for a patient level of roundabout axon guidance receptor homolog 1 (ROBO1) expression as compared with a mean level of ROBO1 expression for non-diabetic, conspecific individuals; and determining if the patient level of ROBO1 expression is significantly higher than the non-diabetic mean level at a significance level of p<0.05; and
(b) administering an SDF-1 agonist to the patient if the patient level of ROBO1 expression is significantly higher at a significance level of p<0.05 than the non-diabetic mean level of ROBO1 expression; wherein the SDF-1 agonist is CTCE-0214.
2. The method of claim 1 , further comprising assaying T cells from the patient for levels of C-X-C chemokine receptor type 4 (CXCR4); and wherein said administering step is conducted if the expression levels of both CXCR4 and ROBO1 are significantly higher at a significance level of b<0.05 than the respective non-diabetic mean levels.
3. The method of claim 1 further comprising assaying ROBO1 protein.
4. The method of claim 1 further comprising assaying Robo1 mRNA.
5. The method of claim 1 , further comprising assaying one or more additional biomarkers associated with autoimmune diabetes, wherein said one or more additional biomarkers comprise one or more biomarkers other than ROBO1; and wherein said administering step is conducted if the expression levels of both ROBO1 and one or more additional biomarkers are significantly higher than the respective non-diabetic mean levels at a significance level of p<0.05.
6. The method of claim 1 , further comprising the step of assaying T cells from the patient for the patient level of ROBO1 expression on at least one additional date to monitor the temporal progression of autoimmune diabetes.
7. The method of claim 1 , further comprising the step of administering Slit homolog 2 protein (SLIT2) to the patient if the patient level of ROBO1 expression is significantly higher than the non-diabetic mean level of ROBO1 expression at a significance level of p<0.05.
8. The method of claim 7 , further comprising the step of administering the CTCE-0214 to the patient at a dose of about 10 mg per kg.
9. The method of claim 7 further comprising assaying CD3 T cells from the patient for expression levels of ROBO1.
10. The method of claim 1 , further comprising the step of administering the SDF-1 agonist to the patient once per week.
11. The method of claim 2 , wherein the assayed T cells are CD3 T cells.
12. The method of claim 2 , wherein the assayed T cells are CD4 T cells.
13. The method of claim 2 , wherein the assayed T cells are CD8 T cells.