Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practices regarding immune monitoring of KT among transplant clinicians and clinical pathologists in Korea and eventually provide a basis for the establishment of harmonized immune monitoring guidelines in KT were administered as part of a Korean Society for Transplantation Sponsored Research Project. The survey results revealed significant variations in IM protocols and interpretation of tests affecting treatment decisions between institutes. Moreover, the results revealed a need to expand the histocompatibility tests into high resolution HLA typing in multiple loci and non-HLA antibody tests that facilitate the epitope analysis and eventually virtual crossmatching. The results of the questionnaire survey from clinical pathologists are addressing the urgent need for the standardization of interpretation and harmonization of results reporting in single antigen bead based HLA antibody identification. Finally, communication between clinicians and clinical pathologists to meet the clinical expectations regarding various immune monitoring tests is needed.
Academies and Institutes ; Consensus ; Decision Making ; Histocompatibility ; Histocompatibility Testing ; Kidney Transplantation ; Korea* ; Monitoring, Immunologic* ; Transplants

Vitamins are micronutrients which are essential for the maintenance of biological responses including immune system. Hence, vitamin deficiency increases a risk of infectious, allergic, and inflammatory diseases. Accumulating evidence has recently revealed the molecular and cellular mechanisms of vitamin-mediated regulation in the active and quiescent immune responses. In this review, we focus on the immunologic roles of vitamins in the regulation of homeostasis and surveillance in the gut.
Avitaminosis ; Energy Metabolism ; Homeostasis* ; Immune System ; Immunoglobulin A ; Inflammation ; Micronutrients ; Monitoring, Immunologic* ; Vitamins*

We consecutively enrolled 82 kidney transplant recipients (KTRs) with stable renal function and 24 KTRs who underwent indication biopsy to compare the histological grading of renal allografts with the activity of circulating T lymphocyte subsets and monocytes determined by flow cytometry, which were obtained at 2 weeks after kidney transplantation (KT) and at the time of indication biopsy, respectively. The sum of the scores of glomerulitis (g) + peritubular capillaritis (ptc), inflammation (i) + tubulitis (t), interstitial fibrosis (ci) + tubular atrophy (ct), and fibrointimal thickening (cv) + arteriolar hyaline thickening (ah) was used to assign a histological grade to the renal allograft samples. The frequencies of CD4⁺HLA-DR⁺/CD4⁺ T cells and CD8⁺HLA-DR⁺/CD8⁺ T cells were significantly increased in KTRs with a microcirculation inflammation (MI) sum score ≥ 1 when compared with KTRs with an MI sum score = 0 as well as stable KTRs. In these 2 subsets, only CD4⁺HLA-DR⁺/CD4⁺ T cells were positively correlated with MI sum scores. Analysis using the receiver operating characteristic (ROC) curve showed that antibody-mediated rejection (AMR) could be predicted with a sensitivity of 80.0% and a specificity of 94.7%, using a cutoff value of 29.6% frequency of CD4⁺HLA-DR⁺/CD4⁺ T cells. MI was significantly associated with an increased frequency of activated T lymphocytes expressing human leukocyte antigen-antigen D related (HLA-DR). Further studies should focus on validating the utility of circulating CD4⁺HLA-DR⁺/CD4⁺ T cells as a noninvasive, immunologic monitoring tool for the prediction of AMR.
Allografts ; Atrophy ; Biopsy ; Fibrosis ; Flow Cytometry ; HLA-DR Antigens* ; Humans ; Hyalin ; Inflammation* ; Kidney Transplantation ; Kidney* ; Leukocytes ; Microcirculation* ; Monitoring, Immunologic ; Monocytes ; ROC Curve ; Sensitivity and Specificity ; T-Lymphocyte Subsets ; T-Lymphocytes* ; Transplant Recipients*

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications.
Antibodies, Monoclonal ; Cytomegalovirus* ; Enzyme-Linked Immunospot Assay ; Flow Cytometry ; Graft Survival ; Immunity, Cellular ; Immunophenotyping ; Major Histocompatibility Complex ; Methods ; Monitoring, Immunologic ; Organ Transplantation* ; Transplants*

Sepsis induced by burns, trauma, and surgical stress, remains a major cause of death of patients in ICUs. A growing number of evidence shows that sepsis may result in dysfunction of innate and adaptive immune system, including the abnormal disorder of immune response of T lymphocytes, regulatory T lymphocytes, and dendritic cells, resulting in a state of immune depression. It is of great significance that dynamic monitoring of immune function and the related indicators might help to assess the risk of secondary infection, the prognosis of septic patients, and to guide the treatment of severe sepsis.
Burns ; immunology ; Dendritic Cells ; immunology ; Humans ; Intensive Care Units ; Monitoring, Immunologic ; Prognosis ; Sepsis ; immunology ; T-Lymphocytes, Regulatory ; immunology

BACKGROUND/AIMS: Advanced human immunodeficiency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression. METHODS: A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA < 50 copies/mL maintained for 4 years or longer and who were receiving HAART. Advanced HIV infection was defined as a baseline CD4 T cell count < 200/mm3. Immunologic responders were defined as patients showing immunologic recovery (CD4 T cell counts > or = 500/mm3 at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation. RESULTS: Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes (cells/mm3 per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope > or = 20 during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery. CONCLUSIONS: The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients.
Adult ; Anti-HIV Agents/therapeutic use ; Antiretroviral Therapy, Highly Active ; Biomarkers/blood ; *CD4 Lymphocyte Count ; Case-Control Studies ; Chi-Square Distribution ; Female ; HIV Infections/*diagnosis/drug therapy/*immunology/virology ; HIV-1/drug effects/genetics/*immunology ; Humans ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Monitoring, Immunologic/*methods ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; RNA, Viral/blood ; Time Factors ; Treatment Outcome ; Viral Load

We report on the usefulness of the ImmuKnow assay in a case of suspected acute cellular rejection after liver transplantation. A 58-year-old male with hepatocellular carcinoma and liver cirrhosis caused by chronic hepatitis C had undergone tumorectomy 2 months previously. Following surgery, the underlying cirrhosis and hepatic encephalopathy were aggravated. The patient had been listed for liver transplantation and underwent cadaveric donor liver transplantation. Approximately 11 days after discharge, the patient developed mild fever and diarrhea and was rehospitalized. A liver biopsy showed histologic features associated with cellular rejection. According to the histopathologic diagnosis, the dosage of tacrolimus was increased from 5 to 7 mg twice daily. After changing the dose, aspartate aminotransferase and alanine aminotransferase were elevated, findings not corresponding to the former diagnosis. Hepatitis C virus (HCV) quantitative assay and ImmuKnow assay were performed for further evaluation. High HCV viral load and a very low ATP level detected using the ImmuKnow assay were suggestive of recurrent HCV rather than acute cellular rejection. Two weeks after reducing the immunosuppressant dosage and treating with antiviral therapy using ribavirin, the patient showed clinical improvement with a decrease in HCV viral load and a normal ATP level. Due to overlapping histologic features, acute cellular rejection can be difficult to distinguish from recurrent HCV. As in this case, the ATP level detected using the ImmuKnow assay is considered a reliable marker of cellular immune status. Immune monitoring of transplant patients may assist in making a differential diagnosis and in minimizing the adverse events of immunosuppression.
Adenosine Triphosphate ; Alanine Transaminase ; Aspartate Aminotransferases ; Biopsy ; Cadaver ; Carcinoma, Hepatocellular ; Diagnosis ; Diagnosis, Differential ; Diarrhea ; Fever ; Fibrosis ; Hepacivirus ; Hepatic Encephalopathy ; Hepatitis C ; Hepatitis C, Chronic ; Humans ; Immunosuppression ; Liver Cirrhosis ; Liver Transplantation* ; Liver* ; Male ; Middle Aged ; Monitoring, Immunologic ; Ribavirin ; Tacrolimus ; Tissue Donors ; Viral Load

One of the hallmarks of the adaptive immune system is the specificity of B and T cell receptors. Thanks to somatic recombination, a large repertoire of receptors can be generated within an individual that guarantee the recognition of a vast number of antigens. Monoclonal antibodies have limited applicability, given the high degree of diversity among these receptors, in BCR and TCR monitoring. Furthermore, with regard to cancer, better characterization of complex genomes and the ability to monitor tumor-specific cryptic mutations or translocations are needed to develop better tailored therapies. Novel technologies, by enhancing the ability of BCR and TCR monitoring, can help in the search for minimal residual disease during hematological malignancy diagnosis and follow-up, and can aid in improving bone marrow transplantation techniques. Recently, a novel technology known as next generation sequencing has been developed; this allows the recognition of unique sequences and provides depth of coverage, heterogeneity, and accuracy of sequencing. This provides a powerful tool that, along with microarray analysis for gene expression, may become integral in resolving the remaining key problems in hematology. This review describes the state of the art of this novel technology, its application in the immunological and hematological fields, and the possible benefits it will provide for the hematology and immunology community.
Allergy and Immunology* ; Antibodies, Monoclonal ; Bone Marrow Transplantation ; Diagnosis ; Gene Expression ; Genome ; Hematologic Neoplasms ; Hematology* ; Immune System ; Microarray Analysis ; Monitoring, Immunologic ; Neoplasm, Residual ; Population Characteristics ; Receptors, Antigen, T-Cell ; Recombination, Genetic ; Sensitivity and Specificity

Through consensus, establish a post-marketing scheme and the technical processes to evaluate Chinese medicine's immunotoxicity on a population, as well as its beneficial influences on the immune system. Provide regulations on the collection, storage and transportation of serum samples. This article applies to the post-marketing scientific evaluation of the immunotoxicity of parenterally administered, and for other ways of taking Chinese medicine.
Consensus ; Drug Hypersensitivity ; etiology ; immunology ; Drug Monitoring ; adverse effects ; methods ; standards ; Drugs, Chinese Herbal ; adverse effects ; Expert Testimony ; Humans ; Immunologic Techniques ; methods ; standards ; Product Surveillance, Postmarketing ; methods ; standards ; Th1 Cells ; immunology ; Th2 Cells ; immunology

Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work-up of renal allograft dysfunction-an update. Curr Opin Nephrol Hypertens 8:723-728, 1999). A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the "drug level" era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients.
Biopsy ; Kidney ; Monitoring, Immunologic ; Organothiophosphorus Compounds ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants