Antihuman leukocyte antigen antibody-induced autoimmunity: role in chronic rejection

Nath, Dilip S.; Basha, Haseeb Illias; Mohanakumar, Thalachallour

doi:10.1097/mot.0b013e3283342780

Cited by 65 publications

(55 citation statements)

References 39 publications

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“…A lthough kidney rejection following allotransplantation had been considered to be largely a T-cell mediated phenomenon (1,2), there is growing evidence that B cells and antibodies may play a role in the process (3)(4)(5). In this regard, the nature of the lymphoid cells that infiltrate into the transplanted kidney is of special interest (6,7).…”

Section: Transplantation | Combinatorial Antibody Libraries | Next-gementioning

confidence: 99%

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

Cheng

Torkamani²,

Grover³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.

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Section: Transplantation | Combinatorial Antibody Libraries | Next-gementioning

confidence: 99%

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

Cheng

Torkamani²,

Grover³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…While the mechanism of chronic kidney rejection is far from certain, recent studies have suggested that a large set of genes that encode proteins of the innate and adaptive immune system are expressed in the host during rejection (2). Another interesting immunological feature of transplanted kidneys is the appearance of highly organized ectopic B-cell clusters in the transplant (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys

Grover

Cheng²,

Peng³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The mechanism of chronic rejection of transplanted human kidneys is unknown. An understanding of this process is important because, chronic rejection ultimately leads to loss of the kidney allograft in most transplants. One feature of chronic rejection is the infiltration of ectopic B-cell clusters that are clonal into the transplanted kidney. We now show that the antibodies produced by these B-cells react strongly with the core carbohydrate region of LPS. Since LPS is a costimulatory immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4), these results suggest a mechanism for the selective pressure that leads to clonality of these B-cell clusters and opens the possibility that infection and the attendant exposure to LPS plays a role in the chronic rejection of human kidney transplants. If confirmed by clinical studies, these results suggest that treating patients with signs of chronic rejection with antibiotics may improve kidney allograft survival.

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“…High levels of circulating anti-HLA antibodies are associated with poor intermediate and long term survival. Presence of anti-endothelial antibodies is a strong determinant of CAV progression [6,58,[62][63][64][65][66][67][68]. Presence of non-HLA antibodies against cardiac myosin and vimentin has also been associated with pathogenesis of CAV.…”

Section: Immunobiology and Pathogenesis Of Coronary Allograft Vasculomentioning

confidence: 99%

“…Antibody mediated rejection (AMR) or vascular rejection is associated with anti HLA and antiendothelial antibody formation and has been linked to pathogenesis of CAV [6,[62][63][64]. Anti HLA antibodies can exert effects on allograft through complement dependent and independent pathways.…”

Section: Immunobiology and Pathogenesis Of Coronary Allograft Vasculomentioning

confidence: 99%

“…CAV is multifactorial in origin and is considered to be a form of chronic rejection previously due to the crucial role played by various alloimmune and autoimmune mechanisms in the pathogenesis of CAV [6][7][8]. Although immune mediated factors play a major role, several studies have demonstrated the role of traditional risk factors of coronary artery disease (CAD) in the progression of CAV [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Munagala¹,

Phancao²

2018

obm.transplant

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Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one-year mortality after heart transplantation. Nonetheless, longterm graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Remarkable progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology. Nevertheless, significant knowledge gaps persist in scientific understanding of risk factors, pathogenesis, prevention and treatment of CAV. Further research is warranted to fill these gaps, develop diagnostic modalities to facilitate early detection of CAV, and management strategies to Improve graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.

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Antihuman leukocyte antigen antibody-induced autoimmunity: role in chronic rejection

Cited by 65 publications

References 39 publications

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

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