Abstract
In addition to cellular immune responses, humoral immune responses, mediated by natural antibodies, autoantibodies, and alloantibodies, have increasingly been recognized as causes of organ transplant rejection. In our previous studies, we have demonstrated the induction of antinuclear antibodies against histone H1 and high-mobility group box 1 (HMGB1), in both experimental and clinical liver transplant tolerance. The active induction of antinuclear antibodies is usually an undesirable phenomenon, but it is often observed after liver transplantation. However, the release of nuclear antigens and its suppression by neutralizing antibodies are proposed to be important in the initiation and regulation of immune responses. In this review article, we summarize the current understanding of nuclear antigens and corresponding antinuclear regulatory antibodies (Abregs) on infection, injury, inflammation, transplant rejection, and tolerance induction and discuss the significance of nuclear antigens as diagnostic and therapeutic targets.
Highlights
Transplantation of cells, tissues, or organs is widely used to cure patients with life-threatening diseases or traumatic injuries
Since the early days of experimental and clinical liver transplantation, it has been known that this organ does not always obey the normal rules of transplant rejection (Medawar’s rule of transplantation); for example, all grafts are rejected between unrelated individuals, and the survival rate following liver transplantation is higher than that following the transplantation of other organs [7, 8]
In Dark Agouti (DA) donor livers transplanted into Piebald Virol Glaxo (PVG) recipients, allograft rejection is spontaneously overcome after orthotopic liver transplantation (OLT), resulting in a state of long-lasting and donor-specific tolerance without pharmacological immunosuppression, PVG recipients acutely reject skin, heart, and renal grafts from DA rats [9]
Summary
Transplantation of cells, tissues, or organs is widely used to cure patients with life-threatening diseases or traumatic injuries. Several humoral factors in the serum of a rat tolerogenic OLT model have been identified as immunosuppressive factors, including donorsoluble MHC class I molecules [14], antidonor MHC class II antibodies [15], liver suppressor factor-1 (LSF-1; 40 kDa) [16, 17], LSF-2 (87 kDa), and LSF-3 (10 kDa) [18]. Most of these humoral factors are found only in the experimental OLT model, and it is hard to translate the findings of this animal study to clinical practice. We summarize the current understanding of nuclear antigens and corresponding antinuclear regulatory antibodies (Abregs) on infection, injury, inflammation, transplant rejection, and tolerance induction and discuss the significance of nuclear antigens as diagnostic and therapeutic targets
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