Study Description:
The purpose of this natural history study is to study the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH). This will include detailed longitudinal clinical and immunologic characterization of sHLH, as well as mechanistic studies evaluating inflammasome activation, cytotoxicity, and JAK-STAT signaling. Participants with sHLH will undergo clinical assessment and management along with three research blood draws with the option for additional blood draws at time points such as post-immunosuppressive treatment or treatment escalation and during longer-term follow-up. Participation may be in person or remote, with blood collected and processed locally then shipped to the NIH. Longitudinal clinical information will be recorded, and standard of care will be offered as needed.
Primary Objective:
To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies.
Secondary Objectives:
* To prospectively and longitudinally characterize the predisposing conditions, clinical features, acute triggers, clinical labs, and outcomes of a cohort of individuals meeting sHLH criteria.
* To compare biomarkers and immune profiles between the classically defined sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
* To evaluate for novel immunologic subsets of sHLH with unsupervised analyses using a multi-omic approach, including single-cell transcriptomics and proteomics.
* To evaluate for rare, protein-altering variants in genes associated with cytotoxicity, inflammasome activation, or immunoregulation via (optional) co-enrollment in NIAID Centralized Sequencing protocol.
Primary Endpoint:
Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions.
Secondary Endpoints:
* Characterize the longitudinal clinical course of sHLH, including relapse rates and predictors of key clinical outcomes at one year after diagnosis.
* Identify differences in clinical and/or immunologic profiles between sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
* To evaluate for novel immunologic profiles in sHLH using multi-omic unsupervised analyses.
* Identify new genetic determinants of susceptibility to sHLH in the setting of different predisposing conditions.
The purpose of this natural history study is to study the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH). This will include detailed longitudinal clinical and immunologic characterization of sHLH, as well as mechanistic studies evaluating inflammasome activation, cytotoxicity, and JAK-STAT signaling. Participants with sHLH will undergo clinical assessment and management along with three research blood draws with the option for additional blood draws at time points such as post-immunosuppressive treatment or treatment escalation and during longer-term follow-up. Participation may be in person or remote, with blood collected and processed locally then shipped to the NIH. Longitudinal clinical information will be recorded, and standard of care will be offered as needed.
Primary Objective:
To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies.
Secondary Objectives:
* To prospectively and longitudinally characterize the predisposing conditions, clinical features, acute triggers, clinical labs, and outcomes of a cohort of individuals meeting sHLH criteria.
* To compare biomarkers and immune profiles between the classically defined sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
* To evaluate for novel immunologic subsets of sHLH with unsupervised analyses using a multi-omic approach, including single-cell transcriptomics and proteomics.
* To evaluate for rare, protein-altering variants in genes associated with cytotoxicity, inflammasome activation, or immunoregulation via (optional) co-enrollment in NIAID Centralized Sequencing protocol.
Primary Endpoint:
Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions.
Secondary Endpoints:
* Characterize the longitudinal clinical course of sHLH, including relapse rates and predictors of key clinical outcomes at one year after diagnosis.
* Identify differences in clinical and/or immunologic profiles between sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
* To evaluate for novel immunologic profiles in sHLH using multi-omic unsupervised analyses.
* Identify new genetic determinants of susceptibility to sHLH in the setting of different predisposing conditions.
Visit ClinicalTrials.gov for details.
Contact Information
Office/Contact: NIH Clinical Center Office of Patient Recruitment (OPR)
Phone: 800-411-1222
TTY: TTY dial 711
Email: ccopr@nih.gov