Biology subjects

Rabant, M.

Publications and source records attributed to Rabant, M..

3 recordsLinked to original sources

bioRxiv2026

Non-HLA antibodies worsen the histological phenotype and prognosis of antibody mediated rejection in kidney allografts

IntroductionAntibody-mediated rejection (AMR) remains a leading cause of kidney allograft failure, with both HLA and non-HLA antibodies implicated in its pathogenesis. The contribution of non-HLA antibodies (non-HLA Abs) to microvascular inflammation (MVI) and graft outcome, particularly in cases lacking donor-specific anti-HLA antibodies (HLA-DSAs), remains incompletely understood. MethodsWe analyzed 571 post-transplant serum samples from 326 patients with histological features of AMR (AMRh) and 164 stable controls. Non-HLA Abs were detected using the previously developed Non-HLA Antibody Detection Immunoassay (NHADIA), and associations were examined with histological lesions, AMRh persistence, and graft outcomes. Biopsies were scored according to Banff 2022 criteria, and patients were stratified by HLA-DSA and NHADIA status. ResultsNHADIA values were significantly higher in AMRh patients compared to controls (P=0.0001), regardless of HLA-DSA status. NHADIA values correlated with the severity of glomerulitis, peritubular capillaritis and global MVI scores. In AMRh patients with HLA-DSAs, non-HLA Abs remained independently associated with MVI severity. Follow-up biopsies revealed persistent AMR lesions in patients with both HLA-DSAs and non-HLA Abs. Allograft survival was lowest in double-positive patients, and NHADIA positivity independently predicted graft loss (HR=2.25, 95% CI: 1.03-4.92, P=0.042). Incorporating NHADIA into the Banff classification reclassified 61% of AMRh cases as "double-positive AMRh," and identified new subgroups with significant prognostic differences. ConclusionPost-transplant detection of non-HLA antibodies identifies a distinct subset of AMR with more severe histology and worse graft prognosis, particularly when coexisting with HLA-DSAs. Integrating non-HLA Ab testing into current diagnostic frameworks may refine AMR classification and improve risk stratification. TRANSLATIONAL STATEMENTThis study highlights the clinical relevance of non-HLA antibodies, identified using our innovative endothelial cell-based assay (NHADIA), in kidney transplant recipients. Their presence is associated with more severe antibody-mediated rejection (AMR) and poorer graft outcomes, even in the absence of donor-specific HLA antibodies. Incorporating non-HLA antibody detection into routine post-transplant evaluation may allow clinicians to better identify high-risk patients, including those previously classified as DSA-negative AMR. This expanded immunological profiling refines AMR diagnosis, improves risk stratification, and opens new avenues for personalized immunosuppressive strategies, ultimately enhancing long-term graft survival and patient care.

pathology↗

bioRxiv2021

Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize viral RNA directly in infected cells are critical to analyze its replication cycle, screen for therapeutic molecules or study infections in human tissue. Here, we report the design, validation and initial application of fluorescence in situ hybridization (FISH) probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy (EM). We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening and diagnostics.

microbiology↗

bioRxiv2020

Heterozygous RELA mutations cause early-onset systemic lupus erythematosus by hijacking the NF-κB pathway towards transcriptional activation of type-I Interferon genes

Systemic Lupus Erythematosus (SLE) is an autoimmune and inflammatory disease characterized by uncontrolled production of autoantibodies and inflammatory cytokines such as the type-I interferons. Due to the lack of precise pathophysiological mechanisms, treatments are based on broad unspecific immunossupression. To identify genetic factors associated with SLE we performed whole exome sequencing and identified two RELA heterozygous activating mutations in 3 early-onset and familial SLE cases. The corresponding RELA/p65 mutant were abundant in the nucleus but poorly activate transcription of genes controlled by NF-{kappa}B consensus sequences. The co-expression of the mutant and wild-type RELA/p65 strongly activated the expression of genes controlled by the IFN-consensus sequences. These molecular mechanisms lead to the overproduction of type-I IFN in the patients cells. Our findings highlight a novel mechanism of autoimmunity where these new RELA mutants are transactivating the type-I IFN genes and are thus promoting type-I interferon production and early-onset SLE, thereby paving the way to the identification of new and specific therapeutic targets. SummaryHeterozygous RELA mutations are associated with Systemic Lupus Erythematosus, with increased expression of genes controlled by the IFN-consensus sequences.

immunology↗