Alshekaili Jalila, Al Lawati Batool S H, Althuhli Zahran, Al-Azri Warda, Al-Maawali Almundher, Al-Rashdi Samiya, Al-Mamari Farida, Al-Kindi Mahmood, Al Balushi Hamad, Al-Rawahi Mohammed, Al-Khabori Murtadha, Cook Matthew C
Department of Microbiology and Immunology, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman.
Rheumatology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Rheumatology (Oxford). 2025 Oct 1;64(10):5388-5395. doi: 10.1093/rheumatology/keaf304.
There is a significant genetic contribution to systemic lupus erythematosus (SLE). Monogenic SLE is a distinct form of SLE. We investigated whether familial or known monogenic lupus cases are distinguishable from non-familial lupus by clinical or laboratory phenotype in a population with high rates of consanguinity.
We performed a retrospective case-control study on 24 multiplex families, comprising 62 cases, and 95 non-familial lupus controls. Demographic and Systemic Lupus International Collaborating Clinics criteria were compared between the two groups. Familial cases were also evaluated by whole exome sequencing and cellular phenotyping. Statistical analysis was performed using R Studio.
Familial and non-familial lupus cases were similar although familial cases were younger at presentation (18 y vs 26 y, OR = 0.91, P = 1.61 × 10-5), a higher prevalence of synovitis (OR = 2.7, P = 0.013) and lower prevalence of high level of dsDNA antibodies (OR = 0.25, P = 1.9 × 10-3). Exome sequencing of a subset yielded a diagnostic rate of 36%. Monogenic lupus were distinguished from other familial cases by an even younger age at presentation (6 y vs 19 y, OR = 0.82, P = 2.13 × 10-3), non-biased male-to-female ratio (P = 0.077) and expansion of exhausted CD4+ T cells (CD4+CD45RA+PD-1+) (P = 1.7 × 10-4).
Overall, clinical phenotype is a poor indicator of familial or monogenic lupus. Familial lupus and monogenic familial lupus (MoFL) tend to present at a younger age than the Non-MoFL, exhibit less female bias and in some cases are distinguished by a lymphocyte signature. Consanguinity increases the rate of monogenic familial lupus and these cases can present in adulthood.
系统性红斑狼疮（SLE）有显著的遗传因素。单基因SLE是SLE的一种独特形式。我们调查了在近亲结婚率高的人群中，家族性或已知的单基因狼疮病例在临床或实验室表型上是否与非家族性狼疮有区别。
我们对24个多病例家庭进行了一项回顾性病例对照研究，包括62例患者和95例非家族性狼疮对照。比较了两组的人口统计学特征和系统性红斑狼疮国际协作临床标准。还通过全外显子测序和细胞表型分析对家族性病例进行了评估。使用R Studio进行统计分析。
家族性和非家族性狼疮病例相似，尽管家族性病例发病时年龄较小（18岁对26岁，OR = 0.91，P = 1.61×10 - 5），滑膜炎患病率较高（OR = 2.7，P = 0.013），双链DNA抗体高水平患病率较低（OR = 0.25，P = 1.9×10 - 3）。对一部分病例进行外显子测序的诊断率为36%。单基因狼疮与其他家族性病例的区别在于发病年龄更小（6岁对19岁，OR = 0.82，P = 2.13×10 - 3），男女比例无偏差（P = 0.077）以及耗竭的CD4 + T细胞（CD4 + CD45RA + PD - 1 +）扩增（P = 1.7×10 - 4）。
总体而言，临床表型对于家族性或单基因狼疮是一个较差的指标。家族性狼疮和单基因家族性狼疮（MoFL）往往比非MoFL发病年龄更小，女性偏向性较小，并且在某些情况下以淋巴细胞特征为区别。近亲结婚会增加单基因家族性狼疮的发病率，这些病例可在成年期出现。
