A homozygous loss-of-function C1S mutation is associated with Kikuchi-Fujimoto disease

• Published in: Clinical immunology (Orlando, Fla.) Vol. 252; p. 109646
• Main Authors: Alshekaili, Jalila, Nasr, Iman, Al-Rawahi, Mohammed, Ansari, Zainab, Al Rahbi, Nasser, Al Balushi, Hamed, Al-Zadjali, Shoaib, Al Kindi, Mahmood, Al-Maawali, Almundher, Cook, Matthew C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2023
• Subjects: Adolescent; C1S; Complement; Complement C1s - genetics; Histiocytic Necrotizing Lymphadenitis - complications; Histiocytic Necrotizing Lymphadenitis - genetics; Histiocytic Necrotizing Lymphadenitis - pathology; Humans; Kikuchi-Fujimoto; Loss of Function Mutation; Lupus; Male; Lupus; Systemic lupus erythematosus; C1S; Kikuchi-Fujimoto disease; Extractable nuclear antigen; Kikuchi-Fujimoto; Complement
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2023.109646

Kikuchi-Fujimoto disease (KFD) is a self-limited inflammatory disease of unknown pathogenesis. Familial cases have been described and defects in classical complement components C1q and C4 have been identified in some patients.
We describe genetic and immune investigations of a 16 years old Omani male, a product of consanguineous marriage, who presented with typical clinical and histological features of KFD.
We identified a novel homozygous single base deletion in C1S (c.330del; p. Phe110LeufsTer23) resulting in a defect in the classical complement pathway. The patient was negative for all serological markers of SLE. In contrast, two female siblings (also homozygous for the C1S mutation), one has autoimmune thyroid disease (Hashimoto thyroiditis) and a positive ANA and the other sibling has serology consistent with SLE.
We report the first association between C1s deficiency and KFD.
•Kikuchi-Fujimoto disease (KFD) is a self-limited inflammatory disease of unknown cause.•Possible defects in the classical complement pathway have been identified in some cases of KFD.•We describe a novel C1S loss-of-function mutation in a patient with KFD.•This description might supports an action of complement in KFD pathogenesis.