The sum of the effects of all negative factors on the human body is manifested, including in the form of an imbalance in the work of the immune system, which leads to a violation of the recognition and elimination of foreign substances of the most diverse origin. This is manifested in an increase in the frequency of development of inflammatory processes, the risk of their chronicity and the development of complications, the identification of opportunistic or conditionally pathogenic flora as a pathogen, including those with atypical biological properties and antibiotic resistance. The use of etiotropic chemotherapy alone in the treatment does not allow achieving sufficient control over many infectious diseases. The purpose of this review was to investigate additional, alternative approaches to influencing anti-infective immunity. An analysis of the strategy based on the use of modulation of the immune response in the treatment of patients was carried out and its advantages over traditional antimicrobial treatment were determined. The concept of «immunotherapy» is discussed, which implies a variety of effects on the immune system in order to stop the pathological process. The review highlights the main types of immunotherapy - local, general, combined and monoimmunotherapy, as well as active and passive, specific and nonspecific. The review provides convincing data on the need for immunomodulators to meet a number of requirements, analyzes various ways of classifying them and their areas of application. The necessity of using immunotropic drugs on the basis of a comprehensive examination is emphasized, taking into account the correspondence between the nature of clinical manifestations and the severity of changes in immunological parameters. The analyzed data allow us to conclude that immunomodulatory therapy can be used to restore the function of the immune system to the physiological norm after a severe inflammatory process at the stage of immunorehabilitation.
We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellсept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient’s condition, he resumed taking the prescribed immunosuppressants.
The aim of our study was to specify the features of the HLA system in patients registered on the waiting list for kidney transplantation in the Republic of Bashkortostan. HLA-A, HLA-B, and HLA-DR phenotypes were assayed by polymerase chain reaction using PROTRANS and OLERUP SSP kits. The frequency of antigen occurence was determined as the percentage of individuals with the given antigen to the total number of examined individuals. To determine the patterns of distinct antigens within various HLA combinations, we determined maximal percentage of the antigen frequency in combination with other HLA. The largest number of patients on the waiting list suffered from chronic glomerulonephritis, followed by diabetes mellitus, chronic interstitial nephritis, chronic pyelonephritis and polycystic kidney disease. The occurrence frequency of various HLA and their combinations was established both among all the patients suffering from stage 5 chronic kidney disease, and among patients with regard to each nosological category, and the patterns of various HLA combinations were established. The data obtained have been compared with the study results of patients from the waiting lists for organ transplantation in other regions. HLA-A02 (similar to Brazil, Great Britain), HLA-DR07, HLA-DR04 (like as in Nepal, European population of Kazakhstan, Southern China), HLA-A24 (as in Nepal, Southern China), and combinations of HLA-A02-A03, HLA-A02-DR04, HLA-A02-DR01, HLA-A02-B07, HLA-A03-DR01, HLA-B35-DR01 were most common in the patients with chronic kidney disease which can be considered as risk factor for severe nephropathy. HLA-B15, HLA-B40, HLA-vA30, HLA-A32, HLA-B56, HLA-B60, HLA-DR10 were found at minimal frequency; as well as the following combinations: HLA-A01-A24-B08-DR17, HLA-A01-A68-DR07, HLAA24-B07-B13, HLA-A01-B08-B13, HLA-A02-B35-B38-DR01, HLA-A02-B50-B61-DR07, HLA-A01-B55-DR04, HLA-A02-B55-DR03, HLA-A24-B55-DR13, HLA-A01-A02-B08-DR03, HLA-A02-DR01-DR13. The following antigens were absent among our patients: HLA-A28 (similar to Kuwait); HLA-A11, HLA-A23, HLA-A28, HLA-A33, HLA-B46, HLA-B62;-DR03, HLA-DR14 (as in Kazakhstan); HLAA19, HLA-A43, HLA-B16, HLA-B21, HLA-B22, HLA-B83 and HLA-DR05 (as in Great Britain); HLAB14 (as in Brazil). The results obtained were either similar, or different from the literature data, both in terms of the most common HLA and their combinations with regard of special nephropathy types. The revealed differences can be explained by presence of population-specifical HLA features in the patients from different ethnic groups and living in different geographical areas. The found stable associative links between the disorders and HLA may contribute to better understanding of pathogenesis of the disorders, their early preclinical detection, evaluating risk for development of pathological conditions, thus allowing timely justification of preventive measures.
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