Modulation of endoplasmic reticulum aminopeptidase 2 (ERAP2)-mediated immune response
The present disclosure provides methods of treating subjects having an immune disorder by administering a therapeutically effective amount of an Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) inhibitor to the subject, and optionally an Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) agonist or inhibitor and/or an HLA-Aw19 inhibitor, and also provides methods of identifying subjects having an increased risk for developing an MHC-I-opathy.
1 . A method of treating a subject having Birdshot Chorioretinopathy (BSCR), the method comprising administering to the subject an Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) inhibitor,
wherein the ERAP2 inhibitor comprises an ERAP2 siRNA comprising a sense strand having a nucleotide sequence set forth in one of odd-numbered SEQ ID NOs: 859-2748 and a corresponding antisense strand having a nucleotide sequence set forth in even-numbered SEQ ID NOs: 859-2748; and
wherein the subject has at least one HLA-Aw19 allele.
2 . The method according to claim 1 , wherein the ERAP2 inhibitory nucleic acid molecule comprises an ERAP2 small interfering RNA (siRNA).
3 . The method according to claim 1 , wherein the subject has a plurality of HLA-Aw19 alleles.
4 . The method according to claim 1 , wherein the at least one HLA-Aw19 allele comprises at least one HLA-A*29 allele, at least one HLA-A*30 allele, at least one HLA-A*31 allele, or at least one HLA-A*33 allele.
5 . The method according to claim 1 , wherein the at least one HLA-Aw19 allele comprises at least one HLA-A*29 allele.
6 . The method according to claim 1 , wherein the at least one HLA-Aw19 allele comprises:
i) at least one HLA-A*29 allele and at least one HLA-A*30 allele;
ii) at least one HLA-A*29 allele and at least one HLA-A*31 allele; or
iii) at least one HLA-A*29 allele and at least one HLA-A*33 allele.