Role of HLA Antibodies (Class –I & II) and Infections among Renal Transplantion

Abstract

Chronic kidney disease is iceberg in the world, particularly in developing countries. Progressive chronic kidney disease leads to end-stage renal disease. The end-stage renal disease occurs when the kidneys are no longer able to function at a level that is necessary for day-to-day life. Either dialysis or kidney transplant is the mode of treatment. There is an acute need to increase kidney transplant to offer a better life to end-stage renal disease patients. Access to dialysis and kidney transplant in the developing world is limited because of a shortage of organ, affordability and very expensive treatment for a lifetime. Hence, optimizing renal allograft survival is essential. Health care between urban and rural populations is different due to disparities in wealth and literacy. The most common causes of kidney disease in India in both men and women are diabetes and hypertension. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant at the institute of kidney diseases and research center (IKDRC), Ahmedabad. Antibody-mediated and viral infections lead to rejection. The rationale of the present study was to understand the different mechanisms involved in the molecular pathways of rejections. The study was designed with two main objectives in mind to understand the causes of rejections in spite of best HLA matching. Also, there is a need to address problems involved in kidney transplants like morbidity, rejections, infections and long term survival of the graft 1) To correlate the presence of class-I and class-II antibodies with rejection episodes. 2) To correlate viral infection with rejections. It has been pointed out that the presence of donor-specific antibodies (DSA) in ESRD cases are seen in high-risk patients. Inadequate immunosuppression and non-adherence lead to graft rejection. Denovo DSAs are predominantly directed to donor HLA (human leukocyte antigen) class II mismatches and usually occur during the first year of a kidney transplant, but they can appear anytime, even after several years. To achieve the above objectives the study was planned to monitor pre and post-transplant patients included in our study. Different tests were used to know the immunological status of the patient in the pre and post-transplant period. HLA Typing of patient and donor to know there HLA antigens and matching. Complement mediated Lymphocyte cross-matching for detection of auto and donor-specific IgM and IgG cytotoxic antibody. Flow cytometry cross matches for detection of IgG donor-specific antibodies against T & B cells. The third test used was HLA antibody specificity and titer detection by the Luminex platform. All three test is carried out iv before the transplant. If the screening test was positive then single antigen bead test was advised. These tests were also used in post-transplant monitoring for HLA DSA antibody. Presence of DSA HLA antibody leads to rejection and then graft lost if not treated. Testing of infections like viral, bacterial and fungal was carried out as and when required in pre and post-transplant period. Culture and sensitivity for bacterial and fungal infections and for viral infection detection real-time PCR techniques used. Our study it has been shown that DQ antibodies are associated with significantly reduced graft survival. Importantly, antibody-mediated rejection and graft loss did not occur in patients with low levels of DQ-only antibodies. This report details the DQ DSA incidence and actual 5-year post graft outcomes. The mean serum creatinine and proteinuria were significantly higher in patients who developed HLA-DQ antibodies. The 5-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies. This study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Overall antibody-mediated rejections are an important aspect to deal under the organ transplant outcome. Along with the presence of HLA antibodies, other important causes of rejection are viral infections like CMV (4.5%), BKV (3.7%) HBsAg (1.8%), HCV (3.7%), Ebstain-Bar viruses’ leads to immunomodulation followed rejection.