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MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS

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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  1. MONOCYTE/MACROPHAGES AND C4d IN RENAL ALLOGRAFTS Alex Magil, MD

  2. 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

  3. 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

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

  5. 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

  6. Peritubular Capillary C4d

  7. Acute Cellular Rejection

  8. Suspicious for AHR(C4d +)

  9. Suspicious for AHR (C4d +)

  10. Glomerulitis

  11. Glomerular CD 68+ Cells

  12. Interstitial CD 68+ Cells

  13. 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

  14. Results – Banff 97 Grade

  15. Patient Characteristics

  16. General Histological Results

  17. Glomerular and Interstitial Monocytes 12.9 6.5 3.4 0.2 P < 0.0001 P = 0.0030

  18. Glomerular and PTC Neutrophils 0.9 0.8 0.4 0.3 P = 0.0003 P = 0.0035

  19. Glomerular MO and Outcome 57 21 13 8 P=0.0027 MO/GLOM≥0.5 MO/GLOM<0.5

  20. 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

  21. 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

  22. Acknowledgments Kathryn Tinckam Ognjenka Djurdjev David Landsberg Paul Keown

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