Method and means for treating inflammatory bowel disease
A method of treating inflammatory bowel disease (IBD) comprises providing an intestinal biopsy sample obtained from inflamed tissue of a patient; mechanically treating the sample to obtain a cell suspension; identifying cell surface markers of activated leukocytes selected from T lymphocytes, neutrophil granulocytes, and eosinophil granulocytes in the suspension; raising antibodies against one of more of the activated cells and immobilizing them on a support; providing a column loaded with the support; diverting a portion of the patient's peripheral blood to make it pass through the column before re-infusing it to the patient to make the activated leukocytes couple with antibodies on the support, thereby eliminating them from the blood stream. Also disclosed are corresponding columns and supports, and their use in the method.
1. A tailored leukapheresis column for treating a subject with inflammatory bowel disease (IBD), comprising:
a column comprising immobilized antibodies that have been selected based on the subject's unique inflammatory response and that are directed against cell surface markers of activated leukocytes selected from the group consisting of T lymphocytes, neutrophil granulocytes, and eosinophil granulocytes,
wherein the cell surface markers are identified from activated leukocytes obtained from a biopsy sample from inflamed intestinal tissue of the subject with IBD.
2. The column of claim 1 , wherein said antibodies against activated T lymphocytes are selected from antibody against CD69 and integrin ˜α4β7 antibody.
3. The column of claim 1 , wherein said antibodies against activated neutrophil granulocytes are selected from antibodies against CD66b.
4. The column of claim 1 , wherein said antibodies against activated eosinophil granulocytes are selected from antibodies against CD9.
5. An apparatus for leukapheresis comprising the column of claim 1 , a blood pump coupled in line with the column, and means for coupling the pump and the column to the venous system of the subject.
6. The apparatus of claim 5 , wherein the means of coupling the pump and the column to the venous system of the subject comprise two cannulae.
7. The column of claim 1 , wherein the biopsy sample has been mechanically treated to obtain a cell suspension.
8. An apparatus for leukapheresis comprising the column of claim 1 , a blood pump coupled in line with the column, wherein the pump is coupled to the venous system of the subject.
9. The apparatus of claim 8 , wherein the pump is coupled to the venous system of the subject with two cannulae.
10. A combination of two or more leukapheresis columns of claim 1 coupled in parallel or in line.
11. A method of treating inflammatory bowel disease (IBD) in a subject, comprising:
providing one or more columns of claim 1 ;
diverting a portion of the subject's peripheral blood through the column, thereby eliminating activated leukocytes from the subject's peripheral blood; and
re-infusing the subject's peripheral blood to the subject, thereby treating IBD in the subject.
12. The method of claim 11 , wherein a combination of one or more leukapheresis columns is coupled in parallel or in line.
13. The method of claim 11 , wherein the one or more columns comprises a single column.
14. The method of claim 11 , wherein from about one third to about two thirds of the subject's blood volume is passed through the column in a single treatment.
15. The method of claim 11 , wherein about half of the subject's blood volume is passed through the column in a single treatment.
16. The method of claim 11 , wherein the treatment is repeated at least three times over about a one to three week period.
17. The method of claim 11 , wherein the one or more columns comprise antibodies against CD69 and integrin ˜α4β.
18. The method of claim 11 , wherein the one or more columns comprise antibodies against CD66b.
19. The method of claim 11 , wherein the one or more columns comprise antibodies against CD9.
20. The method of claim 11 , wherein the treatment is repeated at least five times over about a one to three week period.