Abstract: SA-PO247

Eculizumab in Refractory Lupus Nephritis with Thrombotic Microangiopathy

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Nelson, Jessica M., Ohio State University, Columbus, Ohio, United States
  • Birmingham, Daniel J., Ohio State University, Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University, Columbus, Ohio, United States
  • Tumlin, James A., University of Tennessee College of Medicine, Chattanooga, Tennessee, United States
  • Rovin, Brad H., Ohio State University, Columbus, Ohio, United States
Background

A patient with refractory lupus nephritis (LN) developed thrombotic microangiopathy (TMA) and was treated with the anti-C5 monoclonal antibody eculizumab (ECU). The response to ECU was minimal, so we characterized C5 cleavage during ECU therapy.

Methods

Complement component C5 and the membrane attack complex (C5b-9) were measured by the complement laboratory at the University of Iowa. Urine C5a were measured by sandwich ELISA. The C5 cDNA was directly sequenced by Sanger methodology.

Results

A 38 year old Asian woman with SLE had an LN flare (class IV+V) and was treated with 6 months of pulse cyclophosphamide + methylprednisolone. Proteinuria and hematuria persisted and serum complement levels remained depressed. The patient developed Coomb’s negative hemolytic anemia and thrombocytopenia with elevated LDH, prothrombin fragments, and fibrin split products, and was diagnosed with TMA. ECU was started. Complement levels after 3 months of ECU are shown (Table). Although the patient’s platelets improved hemolysis continued, circulating C5b-9 was not suppressed and C5a levels were elevated in the urine. Paradoxically concurrent serum C5 levels were above normal. The C5 exons were sequenced but the single nucleotide polymorphisms (SNP) that alter arginine 885 and block ECU binding were not found. However 2 SNPs that affected the amino acid sequence (V802I and E1437D) were found.

Conclusion

ECU did not effectively block C5 cleavage in this patient, and may have caused elevated circulating C5. These findings may be due to genetic variants in the patient’s C5 gene.

Test

Pre-ECUDuring ECUReference Range
Serum Creatinine (mg/dL)0.70.50.5-1.2
Urine Protein:Creatinine 7.311<0.2
Hemoglobin (g/dL)6.811 (transfused)11.7-15.5
Platelets (k/uL)132196150-400
Haptoglobin (mg/dL)-<3044-215
C3 (mg/dL)265287-200
C4 (mg/dL)2undetc18-53
C5 (mg/dL)-3610-21
Urine C5a (ng/mg creatinine)-20<1
Soluble C5b-9 (mg/L)-0.4<0.3

Funding

  • Clinical Revenue Support