DOUBLE POSITIVE BULGARIAN PATIENTS FOR ANTIBODIES PHOSPHOLIPASE A2 RECEPTOR AND THOMBOSPONDIN TYPE-1 DOMAIN CONTAINING 7A - YES OR NO?

Abstract

According to Jiang et al., disease membranous nephropathy (MN) is with autoimmune origin and that affects renal glomeruli (2024). It presents with the clinical features of nephrotic syndrome and one the leading causes of its development. Disease progresses to end-stage renal failure, which is accompanied by a high mortality rate. The reasons for this are the complications of infections, cardiovascular or malignant diseases. In the etiology of primary membranous nephropathy (PMN), role of serum autoantibodies that bind an antigen that expressed by podocytes in the kidneys is indicated. According to Liu et al., PMN is based on immune dysregulation processes with loss of immune tolerance to self-podocytes and leading in formation of immune complexes (2024). All these mechanisms determine the characteristics of a typical autoimmune disease. In recent years, thrombospondin type-1 domain-containing 7A protein (THSD7A) has emerged as a novel antigen in PMN (Nu et al., 2024). That is why the scientific literature on the pathogenesis of PMN discusses the role of autoantibodies directed against these two antigens - phospholipase A2 receptor (PLA2R) and against THSD7A. According to Liu et al., however, despite the progress made in identifying autoantigens in PMN, pathogenetic mechanisms by which glomeruli are damaged still incompletely understood and controversial (2024). It is known that a standard method for diagnosing MH involves performing renal biopsy. In the etiology of secondary membranous nephropathy (SMN), causes such as various infectious and malignant diseases, damage caused by toxins or drugs, etc. are reported. In our study, we aimed to conduct on the following two tasks: 1) tо determine the positive results in MH for anti-phospholipase A2 receptor antibodies (anti-PLA2R) and anti-thrombospondin type-1 domain-containing 7A protein antibodies (anti-THSD7A) antibodies presented in percentages 2) to determine the presence of results that are simultaneously positive for both serum antibodies in the groups we are studying. In study a total of 113 patients from different groups: with PMN (n = 52), with SMN (n = 12) and other nephropathies (ON) (n = 49). Serum concentration antibodie anti-PLA2R was determined in all patients. For this purpose, we used an ELISA kit from EUROIMMUN, and the values were read on an ELISA reader. We used limit value ≥ 20 RU/ml, which is recommended from test kit manufacture. In this way, we distinguished positive from negative results for anti-PLA2R antibodies. To determine of anti-THSD7A antibodies titer, was used an indirect immunofluorescence assay, also from the company EUROIMMUN. Our data showed that 23 of patients with PMN were negative and 29 from the same group were positive for anti-PLA2R. All patients in the SMN and ON groups were negative from them. The data from group of PMN who were anti-PLA2R negative revealed two positive for anti-THSD7A (8.7%). For the total PMN group, they represent 3.9%. The remaining groups of patients with SMN and ON were also examined for this indicator, but the results obtained were negative. In our study, the results we obtained do not show presence of patients who were simultaneously positive for a two studied indicators in different groups. We found it appropriate to determine the anti-THSD7A index in patients with a negative result for anti-PLA2R.