Scala Enrico, Madonna Stefania, Abeni Damiano, Cecchi Lorenzo, Cocuroccia Barbara, Dattolo Anna, Moretta Gaia, Provini Alessia, Russo Filomena, Sordi Donatella, Pallotta Sabatino, Galluzzo Marco, Talamonti Marina, Villella Valeria, Giani Mauro, Caprini Elisabetta, Albanesi Cristina, Villalta Danilo, Asero Riccardo, Matricardi Paolo Maria
Fondazione Luigi Maria Monti, IDI-IRCCS, Rome, Italy.
SOSD Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy.
Allergy. 2024 Dec;79(12):3415-3429. doi: 10.1111/all.16377. Epub 2024 Nov 4.
The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self-proteins has been extensively studied, IgE responses induced by human-homologous exogenous molecular allergens (HEMAs) remains less understood.
To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.
We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer-ALEX-2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an 'IgE molecular-mimicry index' (IgE-MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE-MMI and AD, its severity, and response to dupilumab.
IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non-HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE-MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3-11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4-37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9-15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7-302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02-0.8) and NPC-2 from dust mites (OR: 0.1, 95% CI: 0.01-0.9).
IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE-MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab.
自身免疫性IgE反应在特应性皮炎（AD）中的作用备受争议。虽然针对自身蛋白的IgE已得到广泛研究，但由人类同源外源性分子变应原（HEMA）诱导的IgE反应仍了解较少。
研究针对HEMA的IgE抗体反应是否与AD、其严重程度及对度普利尤单抗的反应相关。
我们纳入了3325名有过敏性疾病史的参与者，其中577名（17.3%）被诊断为AD。使用IgE微阵列（Allergy Explorer-ALEX-2®，MADX，维也纳）检测针对183种外源性变应原分子的血清IgE抗体。根据国际分类标准，参与者按AD严重程度和临床表型进行分层。对于每位患者，我们制定了一个“IgE分子模拟指数”（IgE-MMI），该指数根据IgE对一组五个HEMA蛋白家族（精氨酸激酶、烯醇化酶（ENO）、亲环蛋白（CYP）、脂质运载蛋白和锰超氧化物歧化酶）的反应性计算得出。采用逻辑回归评估针对HEMA的IgE或IgE-MMI与AD、其严重程度及对度普利尤单抗的反应之间的关联。
与其他患者组相比，重度AD患者中对大多数HEMA（32/48，67%）的IgE致敏显著更常见，但对非HEMA的一小部分（3/135，2.2%）的IgE致敏则不然。IgE-MMI在295/2748（10.7%）无AD的过敏性患者中呈阳性，在缓解期、中度或重度AD患者中分别为58/283（20%）、52/134（39%）和86/160（54%）。它与特定表型密切相关，如屈侧性皮炎（比值比8.4，95%置信区间：6.3 - 11.2）、头颈部皮炎（比值比：16.5，95%置信区间：7.4 - 37.2）和泛发性湿疹（比值比：8.6，95%置信区间：4.9 - 15.6）。对度普利尤单抗反应不佳与针对ENO的IgE抗体相关（比值比：22.7，95%置信区间：1.7 - 302.9），但与针对锰超氧化物歧化酶的IgE抗体呈负相关（比值比：0.1，95%置信区间：0.02 - 0.8）以及与来自尘螨的NPC-2呈负相关（比值比：0.1，95%置信区间：0.01 - 0.9）。
IgE微阵列有助于广泛评估过敏性患者中针对HEMA的IgE。对HEMA的IgE反应性和阳性IgE-MMI可能是重度AD、其临床表型及对度普利尤单抗反应的有价值生物标志物。
