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The clinical implications of the unique glomerular complement deposition pattern in transplant glomerulopathy

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Abstract

The etiology and treatment of transplant glomerulopathy (TG) is not clear. TG is associated with donor-specific antibodies but the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. There is however, little information on C4d deposition in the glomerulus itself. We retrieved random frozen sections from 25 cases with well-established TG by light microscopy (LM) and 25 cases without TG as controls and reviewed the LM and immunofluorescence (nine biopsies were excluded due to inadequate samples). Glomerular complement deposition was assessed in all included biopsies. Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%). This pattern was not present in any NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a proximal complement-mediated process and therapies should focus on proximal complement inhibition.

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Abbreviations

AMR:

Antibody mediated rejection

DSA:

Donor specific antibody

EM:

Electron microscopy

ESRD:

End stage renal disease

GCW:

Glomerular capillary wall

HLA:

Human leucocyte antigen

IF:

Immunofluorescence

LM:

Light microscopy

MPGN:

Membranoproliferative glomerulonephritis

Ptc-C4d:

Peritubular capillary C4d

TG:

Transplant glomerulopathy

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Acknowledgements

We sincerely thank Erica Thomas for her tireless work in the IF lab and her thoughtful processing of all samples in above study as well as Sarah Kiminski who aided in data collection.

Author contributions

PSV participated in concept and research design, writing of the paper, performance of the research and data analysis. RCR participated in research design, performance of the research, approved final version of the paper. LB participated in research design, performance of the research, approved final version of the paper. AJM participated in research design and writing of the paper. YK participated in concept and research design, writing of the paper, performance of the research and data analysis.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, University of Minnesota, Minneapolis, USA

    Priya S. Verghese & Youngki Kim

  2. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA

    Robin C. Reed & Bu Lihong

  3. Department of Surgery, University of Minnesota, Minneapolis, USA

    Arthur J. Matas

Authors
  1. Priya S. Verghese
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  2. Robin C. Reed
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  3. Bu Lihong
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  4. Arthur J. Matas
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  5. Youngki Kim
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Corresponding author

Correspondence to Priya S. Verghese.

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The authors of this manuscript have no conflicts of interest to disclose as described by the Journal of Nephrology.

Research involving human and animal statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. Our study was approved by the University of Minnesota Institutional Review Board.

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Verghese, P.S., Reed, R.C., Lihong, B. et al. The clinical implications of the unique glomerular complement deposition pattern in transplant glomerulopathy. J Nephrol 31, 157–164 (2018). https://doi.org/10.1007/s40620-016-0365-7

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  • DOI: https://doi.org/10.1007/s40620-016-0365-7

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