Abstract: FR-PO727

Autoimmune and Genetic Workup in Post-Transplant C3 Glomerulopathy

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Kumar, Ashwani, Postgraduate Institute of Medical Education & Research, Chandigarh, India
  • Nada, Ritambhra, Postgraduate Institute of Medical Education & Research, Chandigarh, India
  • Ramachandran, Raja, Nehru Hospital, Chandigarh, India
  • Rayat, Charan Singh, Postgraduate Institute of Medical Education & Research, Chandigarh, India
  • Gupta, Krishan Lal L., Nehru Hospital, Chandigarh, India
Background

Post-transplant C3 glomerulopathy (Tx-C3GP) is associated with alternate complement pathway (ACP) dysregulation and the literature is scanty. Hence, serological and genetic workup for Tx-C3GP was performed.

Methods

We performed Tx-C3GP workup in all patients reported during 2010-16. Tests included ACP functional assay (APFA), C3, C4 levels, complement factors H (CFH) and B (CFB) estimation. Paraproteins and autoantibodies to CFH (ab-CFH), CFB (ab-CFB), C3 convertase (C3Nef), PCR for CFH and complement factor H-related 5 (CFHR5) genes were done followed by Sanger sequencing. Clinical outcome of the patients was also recorded.

Results

Twenty-six cases of Tx-C3GP included 11 cases of dense deposit disease (DDD), 10 C3 glomerulonephritis (C3GN) and 5 C3GP (EM not available). Mean age was 31.88 years. Two-thirds presented with graft dysfunction (Mean time; <1 week-C3GN, 8 Months-DDD). Nephrotic syndrome and asymptomatic urine abnormality were present in 17%. Basic disease was known in 50% (DDD-4, C3GN-3, C3GP-5, & Diabetic nephropathy-2) cases. Native kidney histology ranged from normal to membranoproliferative (MP) morphology, whereas in early post-transplant recurrences, it was focal segmental proliferative and MP in late recurrences. We observed low APFA and C3 in all cases. Positive findings in DDD included, low CFH levels, ab-CFH, low CFB levels in 56, 25 and 11%, respectively.

Low CFH levels (22%) and ab-CFH were present in 15% of C3GN. In contrast to DDD, 22% patients of C3GN had low CFB levels and ab-CFB (22%). C3NeF was positive in 44% DDD and 33% of C3GN. We found CFH SNP rs800292 (Val62Ile) in 44% and -18TT insertion in 22% cases of DDD and both SNPs were seen in 11% cases of tx-C3GN. SNP rs1061147 (p.Ala243Ala) and rs1061170 (p.His402Tyr) of CFH were more frequent in tx-C3GN (56% & 45%) and seen lesser in tx-DDD (33% and 11%). SNP rs2274700 (p.Ala473Ala) was equally present (22%) in both the groups. No variant of CFHR5 was present in any tx-C3GP case. 43% of the patients experienced graft loss.

Conclusion

Both DDD and C3GN reccur post-transplant. C3GN has an early recurrence compared to DDD. Low CFH and ab-CFH were evident in DDD, whereas low CFB and ab-CFB are seen in C3GN. Genetic findings for CFH gene revealed difference among variants for these two entities.

Funding

  • Government Support - Non-U.S.