Case Report: A young female with co-morbid SLE and atypical hemolytic uremic syndrome carrying IRF5 risk variants
- 1Nephrology Department of the First Hospital of Jilin University
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.
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BibTeX
@article{zhou2026case,
title = {{Case Report: A young female with co-morbid SLE and atypical hemolytic uremic syndrome carrying IRF5 risk variants}},
author = {Huili Zhou and Wei Liu and Tingting Sun and Li Zhang and Weixia Sun and Wanning Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1966450},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1966450/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: A young female with co-morbid SLE and atypical hemolytic uremic syndrome carrying IRF5 risk variants
AU - Huili Zhou
AU - Wei Liu
AU - Tingting Sun
AU - Li Zhang
AU - Weixia Sun
AU - Wanning Wang
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1966450
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1966450/full
AB - 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.
SN - 1664-3224
ER -