RNA biomarkers for hereditary angioedema
Provided herein are methods and kits for analyzing a biological sample obtained from a subject having, suspected of having, or being at risk for a disease associated with the contact activation system.
1. A method for analyzing a sample, comprising:
(i) providing a biological sample obtained from a subject having, suspected of having, or being at risk for hereditary angioedema (HAE);
(ii) measuring the level of a RNA biomarker set, wherein the RNA biomarker set comprises a messenger RNA encoding mitochondrially-encoded cytochrome C oxidase III (MT-CO3);
(iii) identifying the subject as a subject having HAE based on the level of the RNA biomarker set, an increase of the level of MT-CO3 of the subject from that of a control subject being indicative of the subject having HAE; and
(iv) administering to the subject identified as having HAE in step (iii) an effective amount of a therapeutic agent for treating HAE;
wherein the therapeutic agent is a plasma kallikrein (pKal) inhibitor, a bradykinin 2 receptor (B2R) inhibitor, and/or a Cl esterase inhibitor.
2. The method of claim 1 , wherein the biomarker set consists of 2-10 RNA biomarkers.
3. The method of claim 1 , wherein the biological sample is a serum sample or a plasma sample.
4. The method of claim 1 , wherein the HAE is type I HAE or type II HAE.
5. The method of claim 1 , wherein the RNA biomarker set further comprises a microRNA.
6. The method of claim 1 , wherein step (ii) involves polymerase chain reaction and/or nucleic acid hybridization.
7. The method of claim 1 , wherein the subject is a human patient.
8. The method of claim 7 , wherein the human patient has a history of HAE.
9. The method of claim 1 , wherein the therapeutic agent is lanadelumab, ecallantide, icatibant, or human plasma-derived Cl esterase inhibitor.
10. A method for analyzing a sample, comprising:
(i) providing a biological sample obtained from a subject having, suspected of having, or being at risk for hereditary angioedema (HAE);
(ii) measuring the level of a RNA biomarker set, wherein the RNA biomarker set comprises a messenger RNA encoding mitochondrially-encoded cytochrome C oxidase III (MT-CO3);
(iii) identifying the subject as a subject at risk of HAE attack based on the level of the RNA biomarker set, an increase of the level of MT-CO3 of the subject from that of a control subject being indicative that the subject is at risk of HAE attack; and
(iv) administering to the subject identified as being at risk of HAE attack in step (iii) an effective amount of a therapeutic agent,
wherein the therapeutic agent is a plasma kallikrein (pKal) inhibitor, a bradykinin 2 receptor (B2R) inhibitor, and/or a Cl esterase inhibitor.
11. The method of claim 10 , wherein the therapeutic agent is lanadelumab, ecallantide, icatibant, or human plasma-derived Cl esterase inhibitor.
12. The method of claim 1 , wherein the level of the RNA biomarker set or level of MT-CO3 of the subject is at least 1.1-fold higher than the level of the corresponding RNA biomarker or RNA biomarker set obtained from a control subject.
13. The method of claim 1 , wherein the level of the RNA biomarker set or level of MT-CO3 of the subject is at least 2-fold higher than the level of the corresponding RNA biomarker or RNA biomarker set obtained from a control subject.
14. The method of claim 10 , wherein the biomarker set consists of 2-10 RNA biomarkers.
15. The method of claim 10 , wherein the biological sample is a serum sample or a plasma sample.
16. The method of claim 10 , wherein the HAE is type I HAE or type II HAE.
17. The method of claim 10 , wherein the RNA biomarker set further comprises a microRNA.
18. The method of claim 10 , wherein step (ii) involves polymerase chain reaction and/or nucleic acid hybridization.
19. The method of claim 10 , wherein the subject is a human patient.
20. The method of claim 19 , wherein the human patient has a history of HAE.
21. The method of claim 10 , wherein the level of the RNA biomarker set or level of MT-CO3 of the subject is at least 1.1-fold higher than the level of the corresponding RNA biomarker or RNA biomarker set obtained from a control subject.
22. The method of claim 10 , wherein the level of the RNA biomarker set or level of MT-CO3 of the subject is at least 2-fold higher than the level of the corresponding RNA biomarker or RNA biomarker set obtained from a control subject.
23. The method of claim 1 , wherein the RNA biomarker set further comprises a messenger RNA encoding mitochondrially-encoded NADH:ubiquinone oxidoreductase core subunit 3 (MT-ND3).
24. The method of claim 5 , wherein the microRNA is selected from the group consisting of hsa-miR-16-5p, hsa-miR-19a-3p, hsa-miR-20a-5p, hsa-miR-17-5p, hsa-miR-28-5p, hsa-miR-423-3p, hsa-miR-26a-5p, hsa-miR-1307-3p, hsa-miR-335-3p, hsa-miR-139-5p, hsa-miR-485-5p, hsa-miR-26b-5p, hsa-miR-885-5p, hsa-miR-361-3p, hsa-miR-769-5p, hsa-miR-140-5p, hsa-miR-485-3p, hsa-miR-889-3p, hsa-miR-941, RPL23, hsa-miR-328-3p, and hsa-miR-484.
25. The method of claim 10 , wherein the RNA biomarker set further comprises a messenger RNA encoding mitochondrially-encoded NADH:ubiquinone oxidoreductase core subunit 3 (MT-ND3).
26. The method of claim 17 , wherein the microRNA is selected from the group consisting of hsa-miR-16-5p, hsa-miR-19a-3p, hsa-miR-20a-5p, hsa-miR-17-5p, hsa-miR-28-5p, hsa-miR-423-3p, hsa-miR-26a-5p, hsa-miR-1307-3p, hsa-miR-335-3p, hsa-miR-139-5p, hsa-miR-485-5p, hsa-miR-26b-5p, hsa-miR-885-5p, hsa-miR-361-3p, hsa-miR-769-5p, hsa-miR-140-5p, hsa-miR-485-3p, hsa-miR-889-3p, hsa-miR-941, RPL23, hsa-miR-328-3p, and hsa-miR-484.