1.Mechanisms of allorecognition and xenorecognition in transplantation
Clinical Transplantation and Research 2024;38(4):273-293
Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.
2.Mechanisms of allorecognition and xenorecognition in transplantation
Clinical Transplantation and Research 2024;38(4):273-293
Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.
3.Mechanisms of allorecognition and xenorecognition in transplantation
Clinical Transplantation and Research 2024;38(4):273-293
Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.
4.Mechanisms of allorecognition and xenorecognition in transplantation
Clinical Transplantation and Research 2024;38(4):273-293
Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.
5.Unilateral testicular tuberculosis in a kidney transplant recipient: a case report
Jaeseok YANG ; Yaerim KIM ; Woo Yeong PARK ; Kyubok JIN ; Seungyeup HAN ; Byung Hoon KIM ; Misun CHOE ; Jin Hyuk PAEK
Clinical Transplantation and Research 2024;38(3):235-240
Tuberculosis (TB) of the genitourinary system is a rare form of extrapulmonary TB. Testicular TB is particularly uncommon among kidney transplantation (KT) recipients. Diagnosing testicular TB is challenging due to the nonspecific nature of clinical presentations and ambiguous imaging results. In this report, we describe a case involving a 36-year-old male KT recipient who presented with left scrotal pain. He had undergone a living donor KT 8 years prior and was receiving tacrolimus, mycophenolate mofetil, and prednisolone. Laboratory tests revealed anemia, leukocytosis, and elevated inflammatory markers. Computed tomography showed left scrotal wall thickening and enlargement, suggestive of a left testicular abscess. We discontinued mycophenolate mofetil and administered intravenous antibiotics. Additionally, we performed an incision and drainage of the abscess. However, there was no improvement in his clinical course. Consequently, we performed a radical left orchiectomy. The biopsy revealed extensive chronic granulomatous inflammation with caseous necrosis, consistent with tuberculous orchiepididymitis. A quadruple anti-TB regimen was administered, leading to an improvement in the patient's condition. To the best of our knowledge, this is the first reported case of testicular TB without other organ involvement in KT recipients. Including testicular TB in the differential diagnosis of testicular infections and masses is necessary to avoid unnecessary surgical procedures.
6.Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients:Guidelines by the Korean Society of Infectious Diseases and the Korean Society for Transplantation
Kyungmin HUH ; Sang-Oh LEE ; Jungok KIM ; Su Jin LEE ; Pyoeng Gyun CHOE ; Ji-Man KANG ; Jaeseok YANG ; Heungsup SUNG ; Si-Ho KIM ; Chisook MOON ; Hyeri SEOK ; Hye Jin SHI ; Yu Mi WI ; Su Jin JEONG ; Wan Beom PARK ; Youn Jeong KIM ; Jongman KIM ; Hyung Joon AHN ; Nam Joong KIM ; Kyong Ran PECK ; Myoung Soo KIM ; Sang Il KIM
Infection and Chemotherapy 2024;56(1):101-121
Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients.The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold.Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cellmediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.
7.The effect of periodontitis on recipient outcomes after kidney transplantation
Hyeon-Jin MIN ; Jung-Soo PARK ; Jaeseok YANG ; Jihyun YANG ; Se Won OH ; Sang-Kyung JO ; Won Yong CHO ; Jun Gyo GWON ; Cheol Woong JUNG ; Yang-Jo SEOL ; Shin-Young PARK ; Myung-Gyu KIM
Kidney Research and Clinical Practice 2022;41(1):114-123
Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. Methods: This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results: Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. Conclusion: Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed.
8.The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort
Hee Jung JEON ; Tai Yeon KOO ; Man Ki JU ; Dong-Wan CHAE ; Soo Jin Na CHOI ; Myoung Soo KIM ; Jung-Hwa RYU ; Jong Cheol JEON ; Curie AHN ; Jaeseok YANG ;
Kidney Research and Clinical Practice 2022;41(4):492-507
As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. Methods: The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. Results: From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy-proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. Conclusion: The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.
9.Antithymocyte globulin versus basiliximab induction for kidney transplantation in elderly patients: matchedanalysis within the Korean multicentric registry
Jun Young LEE ; Sung Hwa KIM ; Yeon Ho PARK ; Jae Berm PARK ; Su Hyung LEE ; Jaeseok YANG ; Myoung Soo KIM ; Deok Gie KIM ;
Kidney Research and Clinical Practice 2022;41(5):623-634
Basiliximab (BSX) and antithymocyte globulins (ATGs), are two major immunosuppressive agents commonly used as induction therapy for kidney transplant (KT) recipients. The superiority of ATG over BSX has not been well established, especially in elderly KT recipients with low immunological risk. Methods: A total of 847 elderly (≥60 years old), low-risk KT patients in the Korean Organ Transplantation Registry were propensity score-matched at a 1:2 ratio and compared according to ATG or BSX induction therapy. The primary outcome was patient and graft survival and biopsy-proven acute cellular rejection. The secondary outcome was graft function, BK virus nephropathy, infection, cancer, new-onset diabetes mellitus after transplantation (NODAT), and delayed graft function. Results: In total, 165 patients in the ATG group were matched with 298 patients in the BSX group with average ages of 64.3 and 64.2 years, respectively. During a follow-up of 28.5 ± 10.4 months, the cumulative probabilities of death-censored graft failure at 3 years posttransplantation were 1.3% and 1.4% in ATG and BSX groups, respectively, without a significant difference (p = 0.72). The cumulative probability of NODAT at 3 years posttransplantation was significantly higher in the BSX group (35.6% vs. 21.6%, p = 0.02). The median tacrolimus trough level was significantly lower at 6 months after KT in the ATG group (5.7 ng/mL vs. 6.4 ng/mL, p = 0.001). There were no differences in the other evaluated outcomes. Conclusion: Compared with BSX, in elderly, low-risk KT patients, ATG reduced tacrolimus and steroid requirements without differences in all-cause mortality, rejection, or infection, resulting in a reduced NODAT incidence.
10.Human B1 Cells are the Main Blood Group A-Specific B Cells That Have a Moderate Correlation With Anti-A Antibody Titer
Yixuan XU ; Jae Ghi LEE ; Ji Jing YAN ; Jung Hwa RYU ; Songji XU ; Jaeseok YANG
Annals of Laboratory Medicine 2020;40(1):48-56
BACKGROUND:
Anti-carbohydrate antibody responses, including those of anti-blood group ABO antibodies, are yet to be thoroughly studied in humans. Because anti-ABO antibody-mediated rejection is a key hurdle in ABO-incompatible transplantation, it is important to understand the cellular mechanism of anti-ABO responses. We aimed to identify the main human B cell subsets that produce anti-ABO antibodies by analyzing the correlation between B cell subsets and anti-ABO antibody titers.
METHODS:
Blood group A-binding B cells were analyzed in peritoneal fluid and peripheral blood samples from 43 patients undergoing peritoneal dialysis and 18 healthy volunteers with blood group B or O. The correlation between each blood group A-specific B cell subset and anti-A antibody titer was then analyzed using Pearson's correlation analysis.
RESULTS:
Blood group A-binding B cells were enriched in CD27âºCD43âºCD1c− B1, CD5⺠B1, CD11b⺠B1, and CD27âºCD43âºCD1c+ marginal zone-B1 cells in peripheral blood. Blood group A-specific B1 cells (P=0.029 and R=0.356 for IgM; P=0.049 and R=0.325 for IgG) and marginal zone-B1 cells (P=0.011 and R=0.410 for IgM) were positively correlated with anti-A antibody titer. Further analysis of peritoneal B cells confirmed B1 cell enrichment in the peritoneal cavity but showed no difference in blood group A-specific B1 cell enrichment between the peritoneal cavity and peripheral blood.
CONCLUSIONS
Human B1 cells are the key blood group A-specific B cells that have a moderate correlation with anti-A antibody titer and therefore constitute a potential therapeutic target for successful ABO-incompatible transplantation.

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