MONOCYTEMACROPHAGES AND C4d IN RENAL ALLOGRAFTS

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MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS

• Alex Magil, MD

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BACKGROUND

• ACUTE HUMORAL REJECTION (AHR)
• C split factor C4d generated by Ag-Ab reaction
• C4d binds covalently to PTC endothelium BM
• PTC C4d is a putative marker for AHR
• Associated with poor outcome

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BACKGROUND Contd

• MONOCYTE/MACROPHAGE (MO)
• Component of the inflammatory infiltrate in
  acute rejection
• Prominent numbers associated with poor outcome
• C split factor C5a is chemotactic for MO
• Uncertain whether MO has a role in AHR

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Hypothesis

• There is a significant association between PTC
  C4d deposition and MO infiltration in acute
  allograft rejection

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Study Design

• Compare glomerular interstitial MO PMN
  infiltration in C4d and C4d biopsies
• All biopsies showing strong diffuse PTC C4d
  staining done between Jan. 1, 1999 and June 30,
  2002 C4d Group
• All biopsies showing ACR negative for C4d done
  between Jan. 1, 1999 and Dec. 31, 1999 C4d-
  Group
• For each biopsy - mean no. MO/glomerulus
• - mean no. PMN/glomerulus
• - mean no. CI MO/hpf
• - mean no. PTC PMN/hpf
• All biopsies graded according to Banff 97
  criteria

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Peritubular Capillary C4d
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Acute Cellular Rejection
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Suspicious for AHR (C4d )
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Suspicious for AHR (C4d )
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Glomerulitis
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Glomerular CD 68 Cells
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Interstitial CD 68 Cells
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Pathological Criteria for AHR

• C4d deposition in peritubular capillaries (PTC)
• At least one of the following
• 2.0 PTC neutrophils per hpf
• arterial fibrinoid necrosis
• acute tubular injury
• Circulating donor-specific antibodies
• Mauiyeddi et al JASN 13234-241, 2002

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Results Banff 97 Grade
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Patient Characteristics
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General Histological Results
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Glomerular and Interstitial Monocytes
12.9
6.5
3.4
0.2
P lt 0.0001
P 0.0030
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Glomerular and PTC Neutrophils
0.9
0.8
0.4
0.3
P 0.0003
P 0.0035
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Glomerular MO and Outcome
57
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13
8
P0.0027
MO/GLOM0.5
MO/GLOMlt0.5
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Association of Glomerular MO and C4d with Outcome
51
12
9
8
8
0
6
5
P0.0109
MOlt0.5
MO0.5
MOlt0.5
MO0.5
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Conclusions

• There is a strong association of glomerular and
  interstitial MO infiltration with PTC C4d
• The sensitivity (91) and specificity (93) of
  glomerular MO infiltration (mean MO/GLOM 1.0)
  for the C4d group suggest that glomerular MO be
  added to the current criteria for AHR

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Acknowledgments

• Kathryn Tinckam
• Ognjenka Djurdjev
• David Landsberg
• Paul Keown