Idiotype, anti-idiotype network of autoantibodies. Pathogenetic considerations and clinical application

A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic network exists in these diseases, regulating the production of autoantibodies (idiotypic response). The anti-idiotypic antibodies can be monitored using complementary epitopes, designed according to the "molecular recognition" theory. The role of anti-idiotypic antibodies in neonatal lupus and type 1 diabetes are discussed. In neonatal lupus, mothers with high antiidiotypic antibody activity against anti-La autoantibodies are at lower risk of giving birth to a healthy child, as compared with mothers without anti-idiotypic antibodies. Similarly, the lack of particular anti-idiotypic antibodies, against anti-GAD65 autoantibodies predispose in type 1 diabetes. These findings imply that anti-idiotypic antibodies may confer protection from the harmful effect of autoantibodies in certain autoimmune diseases. A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic network exists in these diseases, regulating the production of autoantibodies (idiotypic response). The anti-idiotypic antibodies can be monitored using complementary epitopes, designed according to the "molecular recognition" theory. The role of antiidiotypic antibodies in neonatal lupus and type 1 diabetes are discussed. In neonatal lupus, mothers with high anti-idiotypic antibody activity against anti-La autoantibodies are at lower risk of giving birth to a healthy child, as compared with mothers without anti-idiotypic antibodies. Similarly, the lack of particular anti-idiotypic antibodies, against anti-GAD65 autoantibodies predispose in type 1 diabetes. These findings imply that anti-idiotypic antibodies may confer protection from the harmful effect of autoantibodies in certain autoimmune diseases

Diagnostic performance of rapid antigen tests (RATs) for SARS-CoV-2 and their efficacy in monitoring the infectiousness of COVID-19 patients

The most widely used test for the diagnosis of SARS-CoV-2 infection is a PCR test. PCR has very high sensitivity and is able to detect very low amounts of RNA. However, many individuals receiving a positive test result in a context of a PCR-based surveillance might be infected with SARS-CoV-2, but they are not contagious at the time of the test. The question arises regards if the cost effective, portable rapid antigen tests (RATs) have a better performance than PCR in identification of infectious individuals. In this direction, we examined the diagnostic performance of RATs from 14 different manufacturers in 400 clinical samples with known rRT-PCR cycles threshold (cT) and 50 control samples. Substantial variability was observed in the limit of detection (LOD) of different RATs (cT = 26.8-34.7). The fluorescence-based RAT exhibited a LOD of cT = 34.7. The use of the most effective RATs leads to true positive rates (sensitivities) of 99.1% and 90.9% for samples with cT <= 30 and cT <= 33, respectively, percentages that can guarantee a sensitivity high enough to identify contagious patients. RAT testing may also substantially reduce the quarantine period for infected individuals without compromising personal or public safety

Investigating the Role of Anti-TPO Antibodies in HIV-Associated Thrombocytopenia before and after Initiation of HAART: A Case-Control Longitudinal Study

This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p p p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750–199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia

Anti-La/SSB antiidiotypic antibodies in maternal serum - A marker of low risk for neonatal lupus in an offspring

Objective. The anti-La/SSB response to major B cell epitopes of La/SSB can be blocked by an active idiotypic/antiidiotypic network, which can be identified using synthetic complementary epitopes deduced from the sequence of the major B cell epitopes of the molecule. This study evaluated the role of this network in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies in the development of neonatal lupus syndrome (NLS). Methods. Sixty-three serum samples collected from anti-Ro/anti-La-positive women during pregnancy or within 6 months after delivery were obtained from the Research Registry for Neonatal Lupus and the PR Interval Dexamethasone Evaluation study. These samples, as well as 30 sera from healthy individuals, were tested in a blinded manner by enzyme-linked immunosorbent assay against, synthetic peptides corresponding to major B cell epitopes and complementary epitopes of La/SSB. Results. Sera from mothers giving birth to a healthy child and having no history of a child with NLS exhibited higher antiidiotypic antibody activity compared with mothers carrying a child with NLS (P < 0.0001) or mothers giving birth to a healthy child but who previously gave birth to a child with NLS (P 0.0151). Sera from mothers of healthy children, which exhibited no apparent epitope activity against amino acids 349-364, revealed a significantly greater frequency of hidden anti-349-364aa epitope responses, blocked by antiidiotypic antibodies, as compared with sera from women pregnant with an affected child (P = 0.0094). Conclusion. The presence of antiidiotypic antibodies to autoantibodies against La/SSB may protect the fetus by blocking pathogenic maternal autoantibodies. Testing for these antiidiotypic responses may be useful in predicting a decreased risk of NLS

Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants.

BACKGROUND: Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). In this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. MATERIALS AND METHODS: Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308 aa and 349-364 aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. RESULTS: All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2 )bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. CONCLUSIONS: Autoimmune sera from patients with pSS and SLE contain anti-idiotypic antibodies targeting a common anti-La/SSB idiotype. These antibodies can be detected using complementary peptides of La/SSB epitopes. The antiidiotypic antibodies mask the anti-La/SSB response. Hidden anti-La/SSB antibodies can be released and detected using complementary epitope analogs