Case Report: A young female with co-morbid SLE and atypical hemolytic uremic syndrome carrying IRF5 risk variants
Year: 2026
Type: article
Study design: Case Report
Abstract: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy and primarily caused by abnormalities in the regulation of the alternative complement pathway, with triggers including infection, pregnancy, surgery and autoimmune disorders like systemic lupus erythematosus (SLE). This paper presents a case of a 21-year-old female carrying a SLE susceptibility variant (c.-12 + 198G>T) in the IRF5 , who presented with concurrent manifestations of SLE and aHUS following diarrhea. The uniqueness of this case lies in the fact that comprehensive whole-exome sequencing revealed no known pathogenic mutations in complement genes (such as CFH, CFI, C3 , etc.), yet identified two heterozygous variants in IRF5 , a core gene of the interferon pathway (the c.-12 + 198G>T risk variant and the c.179A>G missense variant). Following targeted therapy centered on eculizumab, the patient achieved hematologic remission, but the kidney disease progressed to end-stage renal disease (ESRD), and maintenance hemodialysis was initiated. This case suggests that the genetic susceptibility underlying aHUS occurring in the context of SLE may extend beyond the classical complement pathway, and that excessive activation of the interferon pathway may be a key factor in triggering a complement activation ‘storm’ that manifests as aHUS. This observation suggests a possible link between IRF5-related interferon signaling and complement-mediated TMA, and highlights the need for further functional studies. It also emphasizes the importance of early recognition of aHUS and initiation of complement-inhibiting therapy in cases of SLE complicated by TMA.
Source: Frontiers in Immunology
Institution: First Hospital of Jilin University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221811208