T cell and autoantibody profiling for primary immune regulatory disorders

Area of Science:

• Immunology
• Autoimmunity
• Diagnostic Development

Background:

• Primary immune regulatory disorders (PIRD) often lack specific diagnostic criteria, posing challenges in clinical identification.
• Existing tools for characterizing PIRD are limited, frequently leading to diagnoses of exclusion.
• Elevated circulating T follicular helper (cTfh) cells are observed in some autoimmune conditions, but their utility in PIRD diagnosis is not fully established.

Purpose of the Study:

• To develop a novel diagnostic approach for PIRD by integrating cellular and serologic markers of autoimmunity.
• To assess the diagnostic utility of specific CD4+ T cell subsets and autoantibody profiles in patients with PIRD.

Main Methods:

• Recruited 101 pediatric patients with PIRD and 71 healthy controls.
• Utilized flow cytometry to quantify CD4+CXCR5+ T cells expressing CXCR3 and/or CCR6, including cTfh cells (CD4+CXCR5+PD1+).
• Measured IgG and IgA autoantibodies against 1616 protein antigens using a microarray in a subset of patients and controls.

Main Results:

• Increased percentages of cTfh cells and CD4+CXCR5+ T cells expressing CXCR3/CCR6 were observed in a significant proportion of PIRD patients.
• PIRD patients exhibited a higher diversity and number of high-titer IgG and IgA autoantibodies compared to controls.
• An integrated approach combining T cell phenotyping and autoantibody burden achieved 71.4% sensitivity and 85% specificity for PIRD diagnosis.

Conclusions:

• Integrating CD4+ T cell phenotyping with autoantibody profiling offers a promising strategy for diagnosing PIRD.
• This combined approach provides valuable tools for identifying PIRD, particularly in cases lacking clear clinical diagnostic criteria.
• Further research can refine this multi-biomarker strategy for improved PIRD characterization and management.