Mintoff Dillon, Pace Nikolai P
Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Malta.
Department of Dermatology, Mater Dei Hospital, Msida, Malta.
JAMA Dermatol. 2025 Apr 1;161(4):411-415. doi: 10.1001/jamadermatol.2024.5684.
Variation in nicastrin (NCSTN) is associated with a monogenic subtype of hidradenitis suppurativa. Dysregulation of humoral immunity has been suggested as a potential mechanistic link between NCSTN variation and hidradenitis suppurativa. There is a paucity of biomarkers that can predict disease-associated variation.
To investigate whether serum immunoglobulin levels, as a surrogate marker of humoral immunity, can identify individuals with hidradenitis suppurativa who have a specific disease-associated NCSTN variant.
DESIGN, SETTING, AND PARTICIPANTS: Maltese individuals with hidradenitis suppurativa genotyped for a disease-associated NCSTN in-frame deletion prevalent in the local patient cohort were invited to participate in this cross-sectional study from January to July 2023. Participation was restricted to adult individuals with hidradenitis suppurativa without known or suspected pathologies that would be associated with serum immunoglobulin levels. Data were analyzed between October 2023 and December 2023.
Serum immunoglobulin G levels and other hematological paraments were analyzed.
Main outcomes were the associations between serum immunoglobulin levels and an underlying NCSTN variation in individuals with hidradenitis suppurativa.
A total of 125 individuals (64 female individuals [51.2%]) with hidradenitis suppurativa of Maltese ethnicity were recruited in the study, of whom 17 (13.6%) who were from 7 genealogically unrelated families were heterozygous for the disease-associated NCSTN variant. Deletion carriers had a higher serum immunoglobulin G level (1370 mg/dL vs 1140 mg/dL [to convert to g/L, multiply by 0.01]; P < .001). The association between NCSTN variation and elevated immunoglobulin G levels retained significance despite adjusting for multiple confounders, including markers of disease severity, age of recruitment, age of disease onset, treatment with adalimumab, and liver transaminase levels. Serum immunoglobulin G demonstrated a strong discriminatory capacity in identifying patients who were heterozygous for the NCSTN variant.
The results of this cross-sectional study suggest an altered humoral immune state in patients harboring a specific NCSTN variant and support the role of serum immunoglobulin G levels as a potential predictive biomarker of monogenic hidradenitis suppurativa. This may aid in identifying and prioritizing individuals with monogenic hidradenitis suppurativa.
尼卡斯特林（NCSTN）的变异与化脓性汗腺炎的一种单基因亚型相关。体液免疫失调被认为是NCSTN变异与化脓性汗腺炎之间潜在的机制联系。目前缺乏能够预测疾病相关变异的生物标志物。
研究血清免疫球蛋白水平作为体液免疫的替代标志物，是否能够识别出携带特定疾病相关NCSTN变异的化脓性汗腺炎患者。
设计、地点和参与者：2023年1月至7月，邀请了在当地患者队列中对一种与疾病相关的NCSTN框内缺失进行基因分型的马耳他化脓性汗腺炎患者参与这项横断面研究。参与仅限于无已知或疑似与血清免疫球蛋白水平相关病理状况的成年化脓性汗腺炎患者。数据于2023年10月至12月进行分析。
分析血清免疫球蛋白G水平和其他血液学参数。
主要结局是化脓性汗腺炎患者血清免疫球蛋白水平与潜在的NCSTN变异之间的关联。
本研究共招募了125名马耳他族化脓性汗腺炎患者（64名女性患者[51.2%]），其中来自7个无血缘关系家族的17名患者（13.6%）为疾病相关NCSTN变异的杂合子。缺失携带者的血清免疫球蛋白G水平较高（1370mg/dL对1140mg/dL[换算为g/L，乘以0.01]；P＜0.001）。尽管对包括疾病严重程度标志物、招募年龄、疾病发病年龄、阿达木单抗治疗以及肝转氨酶水平在内的多个混杂因素进行了校正，NCSTN变异与免疫球蛋白G水平升高之间的关联仍具有显著性。血清免疫球蛋白G在识别NCSTN变异杂合子患者方面具有很强的鉴别能力。
这项横断面研究的结果表明，携带特定NCSTN变异的患者体液免疫状态发生改变，并支持血清免疫球蛋白G水平作为单基因化脓性汗腺炎潜在预测生物标志物的作用。这可能有助于识别单基因化脓性汗腺炎患者并对其进行优先排序。
