Monocyte macrophages and c4d in renal allografts
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MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS. Alex Magil, MD. 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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MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS

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Monocyte macrophages and c4d in renal allografts

MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS

Alex Magil, MD


Background

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


Background cont d

BACKGROUND Cont’d

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


Hypothesis

Hypothesis

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


Study design

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


Peritubular capillary c4d

Peritubular Capillary C4d


Acute cellular rejection

Acute Cellular Rejection


Suspicious for ahr c4d

Suspicious for AHR(C4d +)


Suspicious for ahr c4d1

Suspicious for AHR (C4d +)


Glomerulitis

Glomerulitis


Glomerular cd 68 cells

Glomerular CD 68+ Cells


Interstitial cd 68 cells

Interstitial CD 68+ Cells


Pathological criteria for ahr

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 13:234-241, 2002


Results banff 97 grade

Results – Banff 97 Grade


Patient characteristics

Patient Characteristics


General histological results

General Histological Results


Glomerular and interstitial monocytes

Glomerular and Interstitial Monocytes

12.9

6.5

3.4

0.2

P < 0.0001

P = 0.0030


Glomerular and ptc neutrophils

Glomerular and PTC Neutrophils

0.9

0.8

0.4

0.3

P = 0.0003

P = 0.0035


Glomerular mo and outcome

Glomerular MO and Outcome

57

21

13

8

P=0.0027

MO/GLOM≥0.5

MO/GLOM<0.5


Association of glomerular mo and c4d with outcome

Association of Glomerular MO and C4d with Outcome

51

12

9

8

0

8

6

5

P=0.0109

MO<0.5

MO≥0.5

MO<0.5

MO≥0.5


Conclusions

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


Acknowledgments

Acknowledgments

Kathryn Tinckam

Ognjenka Djurdjev

David Landsberg

Paul Keown


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