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Abstract: PO1451

Histopathologic Association of Lambda Light Chain Predominance in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Ravipati, Prasanth, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Royal, Virginie, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Bu, Lihong, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Freese, Rebecca L., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Rheault, Michelle N., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Nachman, Patrick H., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Group or Team Name

  • CureGN Investigators
Background

A relative predominance of lambda (λ) over kappa (κ) light chain deposition has long be recognized in IgA Nephropathy (IgAN), which is unlike any other glomerular disease. The reason for this predominance is unknown but may be related to a purported predominance of λ chain expression by gut associated lymphoid tissue B cells. There is limited information regarding the histopathologic findings, if any, associated with predominant λ light chain deposition. Utilizing the CureGN IgAN cohort, we evaluated if predominant λ chain deposition was associated with histologic markers of disease activity by examining MEST characteristics and other variables.

Methods

We divided the CureGN IgAN cohort into two groups based on the intensity of light chain deposition by immunofluorescence. The λ dominant group (LD) was defined by a difference in intensity score of staining of λ minus κ ≥ 1+, and the λ-κ codominant group (KL) by a difference of λ minus κ < 1+. Fisher’s exact test was used to compare the histopathologic changes between the groups with respect to M, E, S, T, scores, total crescents, percent (%) of globally sclerotic glomeruli, % of glomeruli with fibrinoid necrosis, degree of interstitial inflammation, and the intensity of IgG, C1q, and C3 staining.

Results

Among 695 IgAN patients, the kidney biopsy digital images of 269 patients were reviewed by CureGN pathologists and 234 patients had reported λ and κ staining intensity. Of these, 96 (41%) patients were classified as LD (including 7 patients (3%) with λ monotypic staining) and 138 (59%) classified as KL. The two groups did not differ significantly in age, sex, or race. Compared to the KL group, the LD group had a greater frequency of endocapillary hypercellularity (E1, 51.1% vs 36.3% , p=0.04) and IgG staining intensity ≥ 1+ (37.3% vs 21.9% ; p=0.01). There were no significant differences between groups with respect to any other histologic finding.

Conclusion

In IgAN, patients with predominantly λ mesangial deposition are more likely to have increased endocapillary hypercellularity and IgG deposition, two findings previously linked with greater histologic disease activity and possibly worse prognosis. Further studies are needed to elucidate if the predominance of λ chains represents a unique pathogenesis in a subset of patients, or if it imparts a more severe disease course.

Funding

  • NIDDK Support