Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Department of Dermatology, Venereology and Allergology, Medical University of Wroclaw, Wrocław, Poland.
Hum Immunol. 2021 Feb;82(2):121-123. doi: 10.1016/j.humimm.2020.11.004. Epub 2020 Dec 9.
Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to a length of 8-10 amino acids optimal for binding by HLA class I molecules. Although these two enzymes may work separately, but they may also form a heterodimer of enhanced trimming efficiency. We have earlier described a role for ERAP1 single nucleotide polymorphism rs26618 and HLA-C05:01 as risk factors for atopic dermatitis (AD). Here, we examined whether ERAP2 single nucleotide polymorphism rs2248374, determining the presence or absence of the functional form of enzyme, would influence the rs26618 effect. Out of nine rs2248374 - rs26618 genotypic combinations, only one, rs2248374A/A - rs26618C/C, was associated with a risk of AD. Interestingly, the odds ratio increased from 1.10 (CI95%: 0.72; 1.69; p = 0.657) for ERAP2 rs2248374A/A and 1.88 (CI95%: 1.07; 3.28; p = 0.025) for ERAP1 rs26618*C/C to 3.36 (CI95%: 1.41; 8.01; p = 0.004) for their combination, therefore revealing a synergistic effect.
内质网氨肽酶 ERAP1 和 ERAP2 将肽修剪至 8-10 个氨基酸的长度，这是与 HLA Ⅰ类分子结合的最佳长度。尽管这两种酶可能单独发挥作用，但它们也可能形成具有增强修剪效率的异二聚体。我们之前描述了 ERAP1 单核苷酸多态性 rs26618 和 HLA-C05:01 作为特应性皮炎 (AD) 的风险因素。在这里，我们研究了 ERAP2 单核苷酸多态性 rs2248374 是否会影响 rs26618 的作用，该 SNP 决定了酶的功能形式的存在与否。在 rs2248374-rs26618 基因型组合的九个中，只有 rs2248374A/A-rs26618C/C 与 AD 的风险相关。有趣的是，与 ERAP2 rs2248374A/A 和 ERAP1 rs26618*C/C 相比，其组合的比值比从 1.10（95%CI：0.72；1.69；p=0.657）增加到 1.88（95%CI：1.07；3.28；p=0.025），再增加到 3.36（95%CI：1.41；8.01；p=0.004），表明存在协同作用。
