Diagnosis, prevention, and/or treatment of autoimmune diseases
Compositions, methods, and kits are for the diagnosis, prevention and/or treatment of autoimmune diseases by detecting, targeting, and/or eliminating epitope-specific autoimmune cells. The compositions include a conjugate of an epitope and an agent that allows for detecting, targeting, and/or eliminating epitope-specific autoimmune cells.
1. A method of identifying and treating membranous nephropathy (MN) in a patient, comprising:
obtaining a sample from the patient, said sample suspected of containing an anti-PLA2R autoantibody producing B cell population;
contacting said sample with a first PLA2R epitope bound to a label, wherein the first PLA2R epitope comprises SEQ ID NO:13;
determining the amount of binding of the labeled first PLA2R epitope to cells of the anti-PLA2R autoantibody producing B cell population within the sample;
comparing the amount of binding of the labeled first PLA2R epitope in the sample to the amount of binding expected in a control sample from a subject not having MN;
identifying an increase in the amount of binding of the labeled first PLA2R epitope in the sample relative to the amount of binding expected in the control sample thereby identifying the patient as needing treatment for MN; and
administering to the patient a complex comprising a second PLA2R epitope linked to a drug that reduces or eliminates anti-PLA2R autoantibody producing B cell population in the patient, wherein the second PLA2R epitope comprises SEQ ID NO:13, thereby reducing or eliminating the anti-PLA2R autoantibody producing B cell population in the patient, wherein the complex that reduces or eliminates anti-PLA2R autoantibody producing B cell population in the patient has a molecular weight of 14-80 kDa.
2. The method of claim 1 , wherein the sequence of the first or second PLA2R epitope comprises a sequence selected from the group consisting of a sequence as provided in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 2 plus at least about 5% of the sequence provided in SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 5 plus at least about 5% of the sequence provided in SEQ ID NO: 6.
3. The method of claim 1 , wherein the increase in binding in the sample relative to binding in the control sample is at least 10%.
4. The method of claim 1 , wherein the sample is a bodily fluid containing cells.
5. The method of claim 4 , wherein the bodily fluid is selected from the group consisting of blood, plasma, serum, urine, cerebrospinal fluid, and lymph.
6. The method of claim 1 , wherein the method is performed at multiple time points, wherein a decrease in the amount of binding in subsequent time points indicates an amelioration of MN, and wherein an increase in the amount of binding indicates a likelihood of disease progression or relapse.
7. The method of claim 6 , wherein a first time point is before treatment of MN in the patient has begun and a subsequent time point is after initiation of the treatment.
8. The method of claim 1 , wherein the first labeled PLA2R epitope detects B cells or T cells in the sample, and wherein the binding is detected by detecting binding to the B cells or T cells.
9. The method of claim 1 , wherein the label is a fluorophore.
10. The method of claim 9 , wherein the binding is detected using fluorescence activated cell sorting (FACS) or fluorescence microscopy.
11. The method of claim 1 , wherein the label is a radiolabel or a magnetic label.
12. The method of claim 11 , wherein the binding is detected by enzyme-linked assay.
13. The method of claim 12 , wherein the enzyme-linked assay is Enzyme-Linked ImmunoSpot (ELISPOT).
14. The method of claim 11 , wherein the binding is detected by radioimmunoassay or magnetic immunoassay.
15. The method of claim 1 , wherein the drug is selected from the group consisting of one or more Duocarmycin analogues, or cytotoxic drug.
16. The method of claim 1 , wherein an efficacy of reducing or eliminating the anti-PLA2R autoantibody producing B cell population ranges from about 70% to about 100%.
17. The method of claim 1 , wherein the complex also eliminates a T cell population, wherein the T cell population provides T cell help to the anti-PLA2R autoantibody producing B cell population, and wherein an efficacy of reducing or eliminating the T cell population ranges from about 70% to about 100%.
18. The method of claim 1 , wherein the drug is linked to the PLA2R fragment via a valine-citrulline linker.
19. The method of claim 1 , wherein the drug is a cytotoxic drug selected from the group consisting of auristatin, adozelesin, bizelesin, carzelesin, methotrexate, 5-fluorouracil, Doxorubicin, cyclophosphamide, duocarmycin, Epirubicin, cisplatin, 5-fluorouracil and capecitabine.
20. The method of claim 1 , wherein the sample is a biopsy sample of a tissue or organ.
21. The method of claim 1 , wherein the drug is monomethyl auristatin E (MMAE).
22. The method of claim 11 , wherein the complex that reduces or eliminates anti-PLA2R autoantibody producing B cell population in the patient comprises an additional modification.
23. The method of claim 22 , wherein the additional modification is selected from the group consisting of insertion of a 2 to 10 amino acid N-terminal peptide, insertion of a 2 to 10 amino acid C-terminal peptide, attaching a reagent, and adding one or more heterologous sequences.