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Abstract: TH-PO1097

Clinicopathologic Features of CRIM1-Associated Membranous Nephropathy: A Report of Three Cases

Session Information

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States
  • Storey, Aaron J., Arkana Laboratories, Little Rock, Arkansas, United States
  • Stephens, Owen W., Arkana Laboratories, Little Rock, Arkansas, United States
  • Santini, Jose, Nephrology Associates of Central Florida, Orlando, Florida, United States
  • Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
Background

Cysteine rich motor neuron protein-1 (CRIM1) was recently identified as an antigen in membranous nephropathy (MN) by laser capture microdissection and mass spectrometry (MS), but no cases have been described to date. Here, we describe three cases of CRIM1-associated MN and associated clinicopathologic characteristics.

Methods

Protein A/G immunoprecipitation, followed by mass spectrometry (MS) was performed on 158 PLA2R/THSD7A/NELL1/EXT-quadruple negative MN biopsies and 66 cases of membranous lupus nephritis (MLN) for antigen identification. CRIM1 status was confirmed by paraffin immunofluorescence. Histopathologic and clinical characteristics were examined by review of biopsy reports and medical records.

Results

Three patients were identified to be CRIM1 positive, comprising 1.3% of quadruple-negative MN and 1.5% of MLN biopsies. CRIM1 patients had a mean age of 70 ± 12.1 years. All patients had renal dysfunction at presentation, with a mean serum creatinine of 2.2 ± 0.4 mg/dL, mean proteinuria of 5.3 ± 6.7 g/day, and a mean albumin of 3.4 ± 0.5 mg/dL (Table 1). All patients were ANA positive (1:160-1:1280), two of which met criteria for lupus. At follow-up, one of the patients was deceased, one had a transplant, and one had CKD stage IV.

Kidney biopsies demonstrated advanced chronic changes with a mean global glomerulosclerosis of 46.8 ± 7.7%, segmental sclerosis in all cases, and moderate to severe interstitial fibrosis and tubular atrophy in all cases. Immunofluorescence demonstrated 1+ or greater IgG staining in all cases and C3 in 2 of 3 cases. There was no positivity for other immune reactants or extraglomerular staining.

Conclusion

CRIM1 positive MN has a low antigen frequency. This type of MN may be enriched in patients with autoimmune disease and may be associated with a poor prognosis, although data from a larger cohort is required.

Funding

  • NIDDK Support