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Abstract: SA-PO943

Familial Anti-GBM Disease in Zero Human Leukocyte Antigen Mismatch Siblings

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Lepori, Nicola, Mayo Clinic, Rochester, United States
  • Angioi, Andrea, Mayo Clinic, Rochester, United States
  • Cheungpasitporn, Wisit, Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
  • De Vriese, An S., AZ Sint-Jan, Bruges, Belgium
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
Background

Familial anti-GBM disease is extremely rare. The single gene mutations that may play a role in the development of familial anti-GBM disease are currently unidentified.

Methods

A 65-year-old woman presented to our institution with hemoptysis, gross hematuria and oliguria. Physical examination revealed bilateral diffuse wheezes and edema of the lower extremities. The patient was a smoker and had a family history positive for serologic and renal biopsy-proven anti-GBM disease in 2 of her 15 siblings; morover she had been exposed to kerosene during her childhood. Laboratory testing showed hemoglobin (Hb) of 10.2 mg/dL and serum creatinine (sCr) of 12.0 mg/dL. Urinalysis showed 1+proteinuria and hematuria. Serology demonstrated positive anti-GBM IgG antibody test at 2.1 units and negative ANCA. Kidney biopsy showed a crescentic and necrotizing glomerulonephritis, with linear staining of IgG (3+) along the glomerular basement membranes on the IF, consistent with anti-GBM disease. Patient was started on IV metilprednisolone and daily plasmapheresis sessions, followed by oral cyclophosphamide plus prednisone. Nevertheless, due to uremic symptoms, hemodialysis was started. 3 weeks after treatment, anti-GBM IgG antibody became negative and at 3-month follow-up visit renal function had improved and hemodialysis was discontinued. The patient continued to do well with negative anti-GBM antibodies at 15-month follow-up visit with sCr of 1.4 mg/dL without significant proteinuria.
HLA typing from the patient and one of her affected brothers showed they had identical HLA typing (0 of 6 HLA mismatch) and were homozygous for HLA-DR15.

Conclusion

HLA-DR15 is associated with an increased risk of anti-GBM disease, but HLA types in familial anti-GBM disease cases have never been reported. We present the first case of familial anti-GBM disease involving 3 siblings in the same family with a potential link of HLA-DR15 in the development of familial anti-GBM disease.