Kidney Week

Abstract: TH-PO0338

Characterization of IgA, IgA-Immune Complexes and Complement in IgAN Using Laser Microdissection and Mass Spectrometry

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Cara, Anila, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Anila Cara, MD

• Berti, Gian Marco, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Gian Marco Berti, MD, PhD

• Vargas-Brochero, Maria J., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Maria J. Vargas-Brochero, MD, MS

• Juanet, Cristián, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Cristián Juanet, MD

• Russo, Ilario, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Ilario Russo

• Madden, Benjamin J., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Benjamin J. Madden

• Palma, Lilian MP, Universidade Estadual de Campinas, Campinas, SP, Brazil

Lilian MP Palma, DrMed, PhD

• Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Samih H. Nasr, MD

• Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fernando C. Fervenza, MD, PhD, FASN

• Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Sanjeev Sethi, MD, PhD

Background

IgA nephropathy (IgAN) is defined by mesangial deposition of IgA-immune complexes that drive complement-mediated glomerular injury. However, the composition of IgA-immune complexes and complement proteins within glomeruli remains incompletely defined.

Methods

Laser microdissection and mass spectrometry (LMD/MS) were performed on glomeruli from 22 biopsy-proven IgAN cases to characterize Ig and complement proteins.

Results

LMD/MS detected IgA1 and IgA2 in 100% and 82% of cases, respectively. In addition, iBAQ values also showed higher abundance of IgA1 compared to IgA2. J chain was present in 91% of cases, supporting a predominance of mucosal dimeric/multimeric IgA. On the other hand polymeric Ig receptor (PIGR) was identified in only 9% cases suggesting that IgA in IgAN was not derived from secretory IgA. IgG1 was detected in 100% cases; IgG2, IgG3 and IgG4 were not detected (Fig 1A). Complement profiling revealed abundant C3 and terminal pathway components (C5–C9) with minimal C4, indicating predominant activation of the alternative and terminal pathways (Fig 1B). When stratified by histologic lesions (MESTC scoring), higher C3 and C9 abundance was observed in cases with endocapillary hypercellularity (E1) and crescentic (C1/C2) lesions, consistent with increased alternative and terminal pathway activation. Complement regulatory proteins (CFH, CFHR1/2, CD59) were also consistently detected supporting active complement regulation. CFHR1 was significantly increased in mesangial (M1) lesions in the absence of E1 or C1/C2 lesions.

Conclusion

IgAN immune complexes are composed of mucosal-type IgA1/IgA2-IgG1 and are associated with prominent alternative and terminal complement pathway activation.

Figure 1A showing IgA1, IgA2, J chain, PIGR, and IgG subclass on X axis and log2 normalized iBAQ values on the Y axis.
Figure 1B showing complement proteins and complement regulating proteins in 22 cases of IgA nephropathy. The figure shows complement proteins on the Y axis and log2 normalized iBAQ values on the X axis. C3 and C9 are most abundant complement proteins. CFH, CFHR1 and CFHR2 are the most abundant complement regulating proteins. Note the detection of CFB. Red stars indicate the outliers.