Diagnosing and treating inflammatory diseases
A method of diagnosing, monitoring progression of, or monitoring treatment of inflammatory bowel disease comprises determining the levels of CD14 + HLA-DR hi monocytes or monocytes expressing CCR7 or CCR9 or both CCR7 and CCR9 in a sample obtained from a subject, wherein high levels of CD14 + HLA-DR hi monocytes or monocytes expressing CCR7 or CCR9 or both CCR7 and CCR9, or increased levels of CD14 + HLA-DR hi monocytes or monocytes expressing CCR7 or CCR9 or both CCR7 and CCR9 compared to control, indicate the presence or progression of inflammatory bowel disease. Similar methods for diagnosing irritable bowel syndrome are also described. Various companion therapeutic methods and useful binding reagents are also described.
1. A method for treating inflammatory bowel disease comprising:
applying peripheral blood from a patient diagnosed as having inflammatory bowel disease to an apheresis column loaded with a solid support comprising one or more binding reagents capable of specifically binding to a marker of CD14 + HLA-DR hi monocytes comprising CD14, wherein the one or more binding reagents are immobilized directly or indirectly on the support thus removing CD14 + HLA-DR hi monocytes from the peripheral blood of the patient; and
returning the peripheral blood from which CD14 + HLA-DR hi monocytes are removed to the patient.
2. The method of claim 1 wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.
3. The method of claim 1 wherein the binding reagent is an antibody or a chemokine.
4. The method of claim 1 , further comprising selecting a patient for treatment, the patient having an increase in the level of chemokine receptors comprising CD14+ cells, or an increased fraction/cell number of CD14+CCR9 positive cells.
5. The method of claim 1 wherein the apheresis column is loaded with a solid support comprising at least two binding reagents capable of specifically binding to at least two markers of CD14 + HLA-DR hi monocytes, wherein at least one of said markers comprises CD14.
6. The method of claim 1 wherein the binding reagents are selected from an anti-CD14 antibody or a modified version thereof.
7. A method for treating inflammatory bowel disease comprising:
applying peripheral blood from a patient diagnosed as having inflammatory bowel disease to an apheresis column loaded with a solid support comprising one or more binding reagents capable of specifically binding to a marker of CD14 + HLA-DR hi monocytes is selected from CD14, CCR7, and CCR9 wherein the binding reagent is immobilized directly or indirectly on the support thus removing CD14 + HLA-DR hi monocytes from the peripheral blood of the patient; and
returning the peripheral blood from which CD14 + HLA-DR hi monocytes are removed to the patient, and
wherein the binding reagents is selected from CCL19 or a modified version thereof, and wherein the modified CCL19 chemokine comprises the amino acid sequence of SEQ ID NO: 4, and
wherein the amino acid residue at position 78 of SEQ ID NO: 4 is biotinylated, optionally via a spacer group, to permit immobilization of the chemokine on a solid support.
8. The method of claim 7 , wherein the amino acid residue at position 78 of SEQ ID NO: 4 is a lysine residue which is biotinylated via a polyethylene glycol (PEG) spacer group, to permit immobilization of the chemokine on a solid support.
9. The method of claim 8 , wherein the PEG spacer is 3,6-dioxo aminooctanoic acid.