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

Jalila Alshekaili; Iman Nasr; Mohammed Al-Rawahi; Zainab Ansari; Nasser Al Rahbi; Hamed Al Balushi; Shoaib Al-Zadjali; Mahmood Al Kindi; Almundher Al-Maawali; Matthew C Cook

doi:10.1016/j.clim.2023.109646

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

Clin Immunol. 2023 Jul:252:109646. doi: 10.1016/j.clim.2023.109646. Epub 2023 May 18.

Authors

Affiliations

¹ Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman. Electronic address: jalila@squ.edu.om.
² Department of Adult Allergy and Clinical Immunology, The Royal Hospital, Muscat, Oman.
³ Department of Hematology, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
⁴ Department of Pathology, Royal Hospital, Muscat, Oman.
⁵ Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
⁶ Department of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
⁷ Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, NSW, Australia; Department of Medicine, University of Cambridge, United Kingdom; Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, Canberra, NSW, Australia. Electronic address: mc2386@cam.ac.uk.

PMID: 37209807
DOI: 10.1016/j.clim.2023.109646

Abstract

Background: 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.

Material and methods: 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.

Results: 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.

Conclusion: We report the first association between C1s deficiency and KFD.

Keywords: C1S; Complement; Kikuchi-Fujimoto; Lupus.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Complement C1s / genetics
Histiocytic Necrotizing Lymphadenitis* / complications
Histiocytic Necrotizing Lymphadenitis* / genetics
Histiocytic Necrotizing Lymphadenitis* / pathology
Humans
Loss of Function Mutation
Male

Substances

Complement C1s