T-cell and autoantibody profiling for primary immune regulatory disorders.

Background: Limited clinical tools exist for characterizing primary immune regulatory disorders (PIRD). Increased CD4CXCR5PD1 circulating T follicular helper (cTfh) cell percentages have been identified as a marker of active disease in some, but not all, autoimmune disorders.

Objective: We sought to develop a diagnostic approach that combines measurements of cellular and serologic autoimmunity.

A GPVI-platelet-neutrophil-NET axis drives systemic sclerosis.

Systemic sclerosis (SSc) is characterized by progressive fibrosis of skin, lung, and other organs and retains among the highest rates of mortality among autoimmune diseases. We identified activation of circulating neutrophils from patients with diffuse SSc, together with concordant transcriptomic evidence of neutrophil activation in blood, skin, and lungs, and in mice with experimental SSc of skin and lung induced by hypochlorous acid or bleomycin. Neutrophil depletion abrogated experimental SSc, while adoptive transfer of SSc neutrophils induced skin and lung fibrosis in healthy mice, identifying neutrophils as both necessary and sufficient for disease.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls.

T cell and autoantibody profiling for primary immune regulatory disorders.

Background: Limited clinical tools exist for characterizing primary immune regulatory disorders (PIRD), which are often diagnoses of exclusion. Increased CD4CXCR5PD1 circulating T follicular helper (cTfh) cell percentages have been identified as a marker of active disease in some, but not all, autoimmune disorders.

Objective: To develop a diagnostic approach that combines measurements of cellular and serologic autoimmunity.