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Hypertension

Poster Session 1

(131) Urinary Immune Complexome Profiling Allows for Clinical Subphenotype Differentiation in Preeclampsia (PE)

Tuesday, February 13, 2024

10:30 AM – 12:00 PM

Location: Prince George's Exhibit Hall CDE, Lower Atrium Level

Primary Author(s)

Hongwu Jing, PhD

University of Illinois at Chicago
Chicago, IL, United States

Coauthor(s)

Catalin S. Buhimschi, MBA, MD

Professor and Division Director Maternal Fetal Medicine
University of Illinois at Chicago
Chicago, IL, United States
GZ

Guomao Zhao, BS

Laboratory Manager, Perinatal Research
University of Illinois at Chicago
Chicago, IL, United States
William E. Ackerman, IV, MD

Research Associate Professor
University of Illinois at Chicago College of Medicine
Chicago, IL, United States

Presenting Author(s)

IB

Irina A. Buhimschi, MD

Professor and Director, Perinatal Research
University of Illinois at Chicago
Chicago, IL, United States

Objective: Urine of patients with PE harbors unique antigenic proteins in the form of conformational neoepitopes reactive with monoclonal antibodies raised against prototype pre-fibrillar amyloid proteins. The objectives of this study were to discover if 1) the counterpart conformational autoantibodies and immune complexes (ICs) binding to the amyloid neoepitopes are also present in PE urine and 2) if PE clinical subphenotypes are linked to specific antigenic neoepitopes peptides.

Study Design: In a cross-sectional study design we analyzed urine samples of 77 subjects as follows: 1) normotensive nonpregnant (NP-CRL, n=9) or 2) non-PE pregnant persons (P-CRL, n=17, GA: 28±1w); 3) early-onset severe features PE (sPE, n=28, GA: 29±1w) without and 4) with clinically manifest HELLP (sPE+HELLP, n=23, GA: 29±1w). Urine ICs were assayed by ELISA employing C1q (sub-component of ICs) and normalized to creatinine or total protein levels. Urine ICs of a subset of sPE, sPE+HELLP or spontaneous preterm birth (sPTB, n=5) patients were precipitated with polyethylene glycol (PEG), Protein A/G or the amyloidophilic dye Congo red and then subjected to LC/MSMS. Protein identities (IDs) were assigned to functional classes using Scaffold, g:Profiler, Cytoscape with STRING and ClueGO Apps for further analysis.

Results: Compared to CRLs, sPE and sPE+HELLP patients had significantly higher urine IC concentration (Figs. A&B). While quantitatively, there was no difference in IC output between sPE and sPE+HELLP, we observed that different IC enrichments captured distinct ID repertoires. Congo red identified the highest proportion of unique IDs in sPE+HELLP (Fig. C). Protein A/G captured the highest proportion of unique IDs in sPE (Fig. D). Compared to sPE and iPTB, the non-immunoglobulin ID repertoire in sPE+HELLP had higher representation of proteins involved in extracellular processes, hemostasis and protein-lipid interactions.

Conclusion: Our findings highlight the importance of the autoimmune response in PE pathogenesis and support the notion that sPE and HELLP may associate with different repertoires of autoantigens.