Expanding role of antibodies in kidney transplantation

Table 1 The main milestones in the history of role of antibodies in kidney transplantation

Period	Key discoveries	Researchers
Early 20th century	Discovery of blood group antigens	Karl Landsteiner
1950s	Identification of human leukocyte antigens (HLA)	Jean Dausset
1952	First kidney transplant between living donor (mother) and son	N. Oeconomas, J. Hamburger
1954	First successful kidney transplant between identical twins	J P Merrill, J Murray
1964	Development of microcytotoxicity assay for detecting anti-HLA antibodies	Paul Terasaki
1970s-1980s	Elucidation of antibody-mediated graft damage mechanisms	Fritz Bach, John D. Dingell
1983	Introduction of flow cytometry and solid-phase assays	Margaret R Garovoy
1990s	Use of C4d in kidney transplant biopsies	H E Feuchet
2005	Virtual cross-match in kidney transplantation

Table 2 Common examples of allo- and autoantibodies in kidney transplantation

Alloantibodies	ABO blood group antibodies
	Human leukocyte antigen antibodies
	MICA
Autoantibodies	Anti-AT1R
	Anti-ETAR
	Anti-perlecan
	Anti-agrin
	Anti-collagen type IV, III, and I
	Anti-fibronectin
	Anti-vimentin
	Anti-H-Y
	Anti-ARHGDIB
	Anti-PECR
	Anti-PRKCZ
	Anti-Phospholipid antibodies
	Anti-Phospholipase A2 receptors

ATIR: Angiotensin II type 1 receptor; ETAR: Endothelin A receptor; MICA: Major histocompatibility complex class I-related chain antigens; ARHGDIB: Rho guanine nucleotide exchange factor 2; PECR: Peroxisomal trans-2-enoyl-CoA reductase; PRKCZ: Protein kinase C zeta type.

Table 3 Main updates in the nomenclature and classification of antibody-mediated rejection in the Banff classification (1991 to 2019)

Banff meetings, years	Category 2 Antibody-mediated rejection1	Basis of diagnosis and classification
Banff ‘93	Hyperacute rejection	Clinical criteria only
Banff ‘97	Antibody-mediated rejection (AMR)
	Hyperacute
	Accelerated acute
Banff ’97 update (2001)	Diagnostic criteria for acute antibody-mediated rejection were developed	Histological criteria
	Three types were described as: Types I. ATN-like; II. Capillary; III. Arterial	Immunohistopathological criteria
		Serological criteria
Banff ‘05	Diagnostic criteria for chronic antibody-mediated rejection were developed
Banff ‘07	Antibody-mediated changes2
	C4d deposition without rejection
	Acute antibody-mediated rejection
	Chronic active antibody-mediated rejection
Banff ‘13	Antibody-mediated changes
	Acute/active antibody-mediated rejection	Histological
	Chronic active antibody-mediated rejection	Immunohistopathological
	C4d-negative antibody-mediated rejection	Serological
Banff ‘15	Antibody-mediated changes	Molecular criteria
	Acute/active antibody-mediated rejection
	Chronic active antibody-mediated rejection
	C4d staining without evidence of rejection
	Transplant arteriopathy may be seen in chronic
	AMR
Banff ‘17	Antibody-mediated changes
	Active AMR
	Chronic active AMR
	C4d staining without evidence of rejection
	3 criteria for AMR diagnosis remain but C4d
	can substitute for DSA
	DSA testing still advised
	Suspicious for AMR eliminated
Banff ‘19	Category 2: Antibody-mediated changes	Histological
	Active ABMR	Immunohistopathological
	Chronic active ABMR	Serological
	Chronic (inactive) ABMR	Molecular criteria
	C4d staining without evidence of rejection	Electron microscopy

¹May coincide with categories 3, 4 and 5 and 6.

²With the identification of C4d positivity without rejection, the category name was changed from rejection to changes.

Changes in the nomenclature or criteria are in bold face.

Table 4 Examples of some traditional and emerging therapies in kidney transplantation

Traditional therapies	Plasmapheresis
	Immunoadsorption
	Intravenous immunoglobulin
	Anti-CD20 monoclonal antibody rituximab
	Complement inhibitors: Eculizumab, C1 INH
	Proteasome inhibitors: Bortezomib
Emerging therapies	Carfilzomib
	Tocilizumab
	Clazakizumab
	Daratumumab
	Belimumab
	Imlifidase
	Ofatumumab
	Obinutuzumab
	Inebilizumab