Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

Table 1

Common immunosuppressive agents.

Number	Drugs	Mechanism of action	Effect	Reference(s)
1	Mycophenolate sodium, tacrolimus, and azathioprine	Inhibits signals transmitted by IL-2 binding to IL-2R (antiproliferating effect)	Blocks T-cell activation, decreases both cell-mediated and humoral immunities	[27, 133]
2	Glucocorticosteroids: prednisone	Anti-inflammatory	Decreases circulating T-cells and inflammatory cytokines	[27]
3	Polyclonal antithymocyte globulin (ATG) or antilymphocyte globulin (ALG)	Leucocyte depletion/depleting antibodies. Eliminates CD4+ T-cell and B-cell interaction causing B-cell toxicity/apoptosis	Modulation of alloantibody production	[27, 91]
4	Mycophenolate mofetil	Inhibits inosine monophosphate dehydrogenase (IMPDH), inhibits DNA synthesis and protein glycosylation, suppresses expression of CD25, 71, 154, 28	Decreases proliferation of B and T-cells	[27, 133]
5	Anti-CD3 monoclonal antibody	T-cell activation, opsonization, and depletion of antibodies		[27, 133]
6	Tacrolimus, cyclosporine A	Inhibits interleukin- (IL-) 2 production by T-cell calcineurin antagonist, gene transcription, calcineurin inhibitors; causes decrease in gene expression	Decreases both cell-mediated and humoral immunities	[27, 133]
7	Anti-CD 20 monoclonal antibody (chimaeric)	Targets B-cells, depletes B-cell aggregates within allografts	B-cell depletion	[27, 33, 69]
8	Anti-CD 25 monoclonal antibodies (IL-2R chain)	Inhibits IL-2 function		[27]
9	Plasmapheresis, mycophenolic acid	Reduction of antibody titers		[89]
10	Intravenous immunoglobulin (IVIG)	Reduces CD19, CD20, and CD40 expression by B-cells	Blocks the binding of donor-reactive antibodies to target Fc receptors. Regulation of T and B lymphocytes	[33, 89, 135]
11	Rituximab	B binds with CD20 antibody, inhibits B-cell proliferation, decreases the concentration of antibodies. Antibody-dependent cellular cytotoxicity, direct signaling, and antibody-mediated cytotoxicity	Decreases the population of CD20 B-cells.	[33, 77, 133]
12	Plasmapheresis	Removal of DSA in circulation (elimination of DSA)	Reducing the antibody load	[91, 110]
13	Immunoadsorption	Treatment of multiple plasma volumes		[69]
14	OKT3 (murine) anti-CD3/TCR monoclonal antibodies	TCR comodulates with CD3		[90]
15	Eculizumab (humanized monoclonal antibody)	Binds to the C5 protein with high affinity, thereby inhibiting conversion of C5 to C5b.	Preventing formation of the membrane attack complex (C5–9)	[110]