Slide 1PUBLICATIONS Racusen/Solez meeting report for AJT. Racusen/Solez meeting report for AJT. Manuscript on antibody-mediated rejection. Manuscript on antibody-mediated rejection. Manuscript on recurrent autoimmune hepatitis. Manuscript on recurrent autoimmune hepatitis. The editor of the Journal of Heart and Lung Transplantation (Dr. James Kirklin) requested a written set of suggestions from the Banff working group to be forwarded to the council of the International Society of Heart and Lung Transplantation The editor of the Journal of Heart and Lung Transplantation (Dr. James Kirklin) requested a written set of suggestions from the Banff working group to be forwarded to the council of the International Society of Heart and Lung Transplantation

Slide 2 Criteria for Acute Antibody Mediated Rejection (Provisional - Need 1, 2, and 3) 1. Morphologic evidence of acute tissue injury, such as: a. acute tubular injury b. neutrophils and/or monos in PTC and/or glomeruli, or c. fibrinoid necrosis and transmural inflammation in arteries 1. Morphologic evidence of acute tissue injury, such as: a. acute tubular injury b. neutrophils and/or monos in PTC and/or glomeruli, or c. fibrinoid necrosis and transmural inflammation in arteries 2. Immunopathologic evidence for antibody action, such as : a. C4d in PTC or b. Immunoglobulin and complement in fibrinoid necrosis 2. Immunopathologic evidence for antibody action, such as : a. C4d in PTC or b. Immunoglobulin and complement in fibrinoid necrosis 3. Serologic evidence of anti-HLA or other anti- donor antibodies. 3. Serologic evidence of anti-HLA or other anti- donor antibodies. Comb. cellular and humoral rejection (see next) Comb. cellular and humoral rejection (see next)

Slide 3 Criteria for Acute Antibody Mediated Rejection Samples that meet the criteria for acute cellular rejection (Banff I and II) and have the criterion 2 and 3 above are classified as combined cellular and humoral rejection. Samples that meet the criteria for acute cellular rejection (Banff I and II) and have the criterion 2 and 3 above are classified as combined cellular and humoral rejection.

Slide 4 Chronic Rejection Classification - Current Banff ‘97 Chronic/Scleros. Allograft Nephropathy¤ Chronic/Scleros. Allograft Nephropathy¤ Grade I (mild) Mild interstitial fibrosis and tubular atrophy without (a) or with (b) specific changes suggesting chronic rejection Grade I (mild) Mild interstitial fibrosis and tubular atrophy without (a) or with (b) specific changes suggesting chronic rejection Grade II Moderate interstitial fibrosis and tubular atrophy (moderate) (a) or (b) Grade II Moderate interstitial fibrosis and tubular atrophy (moderate) (a) or (b) Grade III Severe interstitial fibrosis and tubular atrophy and tubular loss(severe) (a) or (b) Grade III Severe interstitial fibrosis and tubular atrophy and tubular loss(severe) (a) or (b)

Slide 5 Chronic Rejection Classification - Current Banff ‘97 cont. ¤ Glomerular and vascular lesions help define type of chronic nephropathy; chronic/recurrent rejection can be diagnosed if typical vascular lesions are seen. ¤ Glomerular and vascular lesions help define type of chronic nephropathy; chronic/recurrent rejection can be diagnosed if typical vascular lesions are seen. (Activity. - Immunologic and fibrotic activity indicators - C4D staining, and presence of mononuclear inflammatory cells in the fibrous arterial intima. PTC splitting and lamination have a significance similar to chronic transplant glomerulopathy. ? Role of collagen subtypes, smooth muscle cell actin,elastic tissue stains, molecular markers. Dan paragraph to come.) (Activity. - Immunologic and fibrotic activity indicators - C4D staining, and presence of mononuclear inflammatory cells in the fibrous arterial intima. PTC splitting and lamination have a significance similar to chronic transplant glomerulopathy. ? Role of collagen subtypes, smooth muscle cell actin,elastic tissue stains, molecular markers. Dan paragraph to come.)

Slide 6 Chronic Rejection Classification - Current Banff ‘97 cont. For studies at least two biopsies, more quantitation For studies at least two biopsies, more quantitation

Slide 7 Chronic Rejection Classification - Hope for the Future after Studies Completed Chronic Allograft Dysfunction Classification 1. No biopsy. Otherwise unexplained chronic progressive dysfunction. 2. Biopsy. Uninstructive/Instructive specific - Acute rejection, recurrent disease, cyclosporine or FK toxicity, hypertensive vasc. disease or: CAN (IF TA, FIT)(1-3) Nonimmunologic. Immunologic Changes - C4d, PTC splitting, Mihatsch light microscopic criteria Chronic Allograft Dysfunction Classification 1. No biopsy. Otherwise unexplained chronic progressive dysfunction. 2. Biopsy. Uninstructive/Instructive specific - Acute rejection, recurrent disease, cyclosporine or FK toxicity, hypertensive vasc. disease or: CAN (IF TA, FIT)(1-3) Nonimmunologic. Immunologic Changes - C4d, PTC splitting, Mihatsch light microscopic criteria