Genetics of Acquired Cytokine Storm Syndromes

  • Grant S. Schulert
  • Kejian ZhangEmail author


Secondary hemophagocytic lymphohistiocytosis (sHLH) has historically been defined as a cytokine storm syndrome (CSS) occurring in the setting of triggers leading to strong immunological activation, without any known genetic predilection. However, recent studies have suggested that existing underlying genetic factors may synergize with particular diseases and/or environmental triggers (including infection, autoimmune/autoinflammatory disorder, or malignant transformation), leading to sHLH. With the recent advances in genetic testing technology, more patients are examined for genetic variations in primary HLH (pHLH) associated genes, including through whole-exome and whole-genome sequencing. This expanding genetic and genomic evidence has revealed HLH as a more complex phenomenon, resulting from specific immune challenges in patients with a susceptible genetic background. Rather than a simple, binary definition of pHLH and sHLH, HLH represents a spectrum of diseases, from a severe complication of common infections (EBV, influenza) to early onset familial diseases that can only be cured by transplantation.


Secondary pHLH sHLH EBV Infections Malignancies Rheumatic diseases MAS Inflammatory Autoimmune and autoinflammatory 


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of RheumatologyUniversity of Cincinnati, College of MedicineCincinnatiUSA
  2. 2.Division of Human Genetics, Children’s Hospital Medical CenterUniversity of Cincinnati, College of MedicineCincinnatiUSA

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