Biology subjects

Fussner, L. A.

Publications and source records attributed to Fussner, L. A..

2 recordsLinked to original sources

bioRxiv2026

Heterogeneous causes of acute respiratory distress syndrome correlate with distinct peripheral polyunsaturated fatty acid metabolites

Acute Respiratory Distress Syndrome (ARDS), a heterogeneous syndrome of hypoxic respiratory failure secondary to dysregulated pulmonary inflammation, is caused by diverse insults. Because of this heterogeneity, mechanisms and treatments are difficult to study. As a treatment, n-3 polyunsaturated fatty acid (PUFA) supplementation has had mixed results. PUFAs and downstream oxylipins are important to pulmonary inflammation but are not well defined in ARDS. We hypothesized that differences in fatty acid metabolism, as measured by levels of n-3 and n-6 PUFAs and oxylipins, are associated with differences in ARDS outcomes, ARDS causes, and inflammation. To test this, PUFAs/oxylipins were measured by LC MS/MS in plasma samples from 90 patients with ARDS. Inflammatory cytokines (IL-6, IL-8) were measured by ELISA. Multivariate linear regressions modeled the relationship between PUFAs/oxylipins, inflammation, and ARDS mortality, severity and cause. Multiple n-3 and n-6 PUFA derived oxylipins were decreased in severe ARDS. We did not detect differences in PUFAs/oxylipins by mortality. PUFAs/oxylipins varied by cause of ARDS, especially between patients with sepsis and those with trauma. Furthermore, specific oxylipins were associated with IL-6 and IL-8. Based on our identification of oxylipins that vary by disease severity and injury, these metabolites should be considered as potential biomarkers and mechanisms of lung repair biomarkers. Furthermore, differences in PUFAs did not directly correlate with changes in oxylipins, suggesting differences in lipid metabolism by etiology of injury. Further consideration of differences in lipid metabolism in ARDS could identify potential subgroups that could benefit from n-3 PUFA supplementation or other therapies.

molecular biology↗

bioRxiv2019

Preferential Binding of Anti-Neutrophil Cytoplasmic Antibodies to an Unexpected Epitope of a Chimeric Proteinase 3 Mutant

ObjectiveProteinase 3 (PR3) is the major antigen for anti-neutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3 anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) recognize different epitopes on PR3. We aimed to study the effect of mutations on PR3 antigenicity. MethodsThe recombinant PR3 variants, iPR3 which is clinically used to detect PR3-ANCAs and iHm5 which contains three point mutations in Epitope 1 and 5 generated for epitope mapping studies, immunoassays and serum samples from patients enrolled in ANCA-associated vasculitis (AAV) clinical trials were used to screen the differential PR3-ANCA binding. Selective binding was determined by inhibition experiments. ResultsRather than a reduced binding of PR3-ANCAs to iHm5, we found substantially increased binding of the majority of PR3-ANCAs to iHm5 compared with iPR3. A monoclonal ANCA (moANCA518) from a patient with GPA was found to selectively bind to iHm5 within the mutation-free Epitope 3 and distant from the point mutations of iHm5 contained in Epitope 1 and 5. Binding of iPR3 to monoclonal antibody MCPR3-2 also induced recognition by moANCA518. ConclusionThe preferential binding of PR3-ANCAs from patients like the selective binding of moANCA518 to iHm5 is conferred by increased antigenicity of Epitope 3 on iHm5. This can also be induced on iPR3 when it is captured by monoclonal antibody MCPR-2. This previously unrecognized characteristic of PR3-ANCA interactions with its target antigen has implications for studying antibody-mediated autoimmune diseases, understanding of variable performance characteristics of immunoassays and design of potential novel treatment approaches.

immunology↗