Kidney Week

Abstract: TH-PO1078

Strong Association of C3 Staining Intensity by Immunofluorescence with Inflammatory Lesions in the Oxford MEST-C Classification in an IgAN Cohort

Session Information

• Pathology and Lab Medicine
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1700 Pathology and Lab Medicine

Authors

• Herlitz, Leal C., Cleveland Clinic Department of Pathology, Cleveland, Ohio, United States

Leal C. Herlitz, MD

• Fatica, Richard A., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States

Richard A. Fatica, MD

• Jiang, Yong Guang, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States

Yong Guang Jiang

• Subahi, Ahmed E., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States

Ahmed E. Subahi, MD

• Moradi, Hamid, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Hamid Moradi

• Ndife, Briana C., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Briana C. Ndife, MPH

• Srinivas, Srini, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Srini Srinivas, MD

• Cavanaugh, Corey J., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States

Corey J. Cavanaugh, DO

Background

The Oxford MEST-C classification of IgAN is widely used to assess activity and chronicity in IgAN but immunofluorescence staining intensity for C3 is not part of the classification. The alternative complement pathway is an important mediator of renal injury in IgAN and complement targeted therapy is now available. We examined the relationship between MEST-C lesions and C3 staining in a contemporaneous IgAN cohort.

Methods

Cases of IgAN were identified from a large U.S. health system which includes a multicenter, multistate kidney biopsy database. MEST-C scores and C3 staining intensities were extracted from pathology reports and clinical data was obtained from the electronic medical record. C3 staining was reported on a 0 to 3+ scale and was analyzed as dichotomous variable, either weak (0-1+) or strong (2-3+). Association between C3 staining and various clinical and pathologic characteristics was evaluated using parametric and non parametric methods. A p-value < 0.05 was considered statistically significant.

Results

A total of 376 IgAN biopsies were examined, 63.3% from male patients with a mean age of 43.1 years and a mean follow-up of 2.0 years. Strong C3 staining (2-3+) was significantly associated with the presence of E, S and C lesions. M and T lesions showed a trend to association with C3 staining, albeit insignificant (Table 1). Further investigation into clinical outcomes is ongoing.

Conclusion

Complement C3 staining shows a strong association with E, S and C lesions in IgAN. While S lesions are often considered chronic, our data suggests that at least a subset of S lesions may be actively inflammatory. Re-evaluation of the MEST-C classification to determine whether C3 staining intensity may help identify active disease at a higher risk of progression is warranted.

Funding

• Commercial Support – Novartis