Abstract: TH-PO1263
Molecular Profiling of Antinephrin Autoantibodies Reveals IgG3/IgG4 Predominance and Shared Immunodominant Epitopes in Recurrent FSGS
Session Information
- Late-Breaking Research Posters
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Lafargue, Marie-Camille, Mass General Brigham Inc, Boston, Massachusetts, United States
- Santarine Laureano, Ana Flavia, Mass General Brigham Inc, Boston, Massachusetts, United States
- Hullekes, Frank E., Mass General Brigham Inc, Boston, Massachusetts, United States
- Verhoeff, Rucháma, Mass General Brigham Inc, Boston, Massachusetts, United States
- Leguern, Christian, Mass General Brigham Inc, Boston, Massachusetts, United States
- Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Riella, Leonardo V., Mass General Brigham Inc, Boston, Massachusetts, United States
Group or Team Name
- On behalf of the TANGO Consortium.
Background
Anti-nephrin autoantibodies have been implicated in FSGS recurrence after kidney transplantation, but the molecular characteristics of the antibody response remain poorly defined. We sought to characterize circulating anti-nephrin antibodies by integrating IgG subclass profiling with epitope mapping in patients with FSGS undergoing kidney transplantation.
Methods
We tested 156 pre-transplant serum samples from patients with FSGS across 23 centers for anti-nephrin IgG by ELISA (positivity cutoff 98 RU/mL). In confirmed positive samples, IgG1-4 subclasses were quantified by ELISA and expressed as percentage of summed subclass signal per patient. Linear epitopes spanning the extracellular domain of nephrin were evaluated to define patterns of antibody recognition and identify shared immunodominant regions.
Results
Of 156 samples, 12 (7.7%) were anti-nephrin IgG positive (130-2168 RU/mL); all 12 developed post-transplant FSGS recurrence. IgG3 predominated in 4 patients (46-73%) and IgG4 in 4 others (59-85%), with 2 co-dominant IgG3/IgG4 responses (Figure 1). One patient (highest IgG, 2168 RU/mL) showed a mixed IgG2/IgG3/IgG4 profile. The 3 lowest-titer patients (130-230 RU/mL) showed flat subclass distributions, likely reflecting greater assay background at low titers. Epitope mapping revealed heterogeneous recognition with striking convergence on shared nephrin regions: epitope 7 was the dominant hotspot (87% of positive patients), followed by epitope 4 (60%). No epitope reactivity was detected in disease controls.
Conclusion
Anti-nephrin autoantibodies associated with recurrent FSGS exhibit a distinct molecular architecture characterized by IgG3/IgG4 subclass predominance and convergence on shared immunodominant nephrin epitopes. Integrated anti-nephrin profiling may improve risk stratification and provide mechanistic insight into FSGS recurrence.
Funding
- Other U.S. Government Support