Clinicopathological correlation and the role of comple- ment C3 deposition in renal diseases associated with monoclonal immunoglobulin

Creative Commons License

Kiki Z., Üner M., Ayhan E. A.

38th European Congress of Pathology, Stockholm, İsveç, 12 - 16 Eylül 2026, (Özet Bildiri)

Özet

Background & Objectives: Renal diseases associated with monoclonal immunoglobulin/paraprotein deposition are heterogeneous, and diagnostic classification and treatment decisions—particularly within the MGRS spectrum—can be challenging. This study aimed to characterize the mor- phologic spectrum of monoclonal gammopathy–associated renal lesions and evaluate the impact of complement C3 deposition on clinical course and treatment response.

Methods: We retrospectively reviewed 104 kidney biopsies from 102 patients (2014-2024). Histology, histochemistry, and immunofluorescence (IgG/IgA/IgM, C3, C1q, kappa/ lambda) were re-evaluated. Clinical data and treatment protocols (clone-directed vs. classical immunosuppression) were retrieved from hospital records and analysed using appropriate statistical tests.

Results: The most frequent diagnostic patterns were pro- liferative glomerulonephritis with monoclonal Ig deposits (PGNMID; 33.7%) and light chain amyloidosis (24%). Complement deposition was identified in 44.2% of biop- sies, being most prevalent in PGNMID (71.4%) and mono-clonal immunoglobulin deposition disease (MIDD; 53.3%). We observed a significant interaction between C3 status and treatment response: in C3-negative cases, clone-directed therapy was significantly more effective in slowing renal functional decline compared to classical immunosuppres- sive/immunomodulatory therapy (p=0.018). Conversely, no significant difference in renal progression was found between treatment groups in C3-positive cases (p=0.582).

Conclusion: Complement C3 deposition is a frequent find- ing in monoclonal gammopathy–associated renal diseases and is strongly associated with specific patterns like PGN- MID and MIDD. Our findings suggest that C3 status in renal biopsies may serve as a crucial biomarker to individualize treatment strategies, as the benefit of clone-directed therapy was primarily evident in patients without C3 deposition.