Abdesselem, H. B. | Search bioRxiv

bioRxiv2025

A New Serological Autoantibody Signature Associated with Multiple Sclerosis

The role of autoantibodies in the pathogenesis of Multiple Sclerosis (MS) remains incompletely understood. In this study, we analyzed serum samples from a cohort of MS patients in Qatar using high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Compared to healthy controls, MS patients showed significantly altered autoantibody responses to 129 proteins, with a notable enrichment in autoantibodies targeting antiviral immune response-related proteins. Machine learning analysis identified a distinct molecular signature comprising 17 differentially expressed autoantibodies, including those against MX1, ISG20, MAX, SUFU, NR1H2, HMGN5, and EPHA10. Among these, autoantibodies against MX1-a key effector in the interferon-alpha/beta signaling pathway-showed the most pronounced increase, with nearly a threefold elevation in MS patients. While MX1 has previously been implicated in MS, this is the first report of autoantibody reactivity against the protein, suggesting a potential role in disease onset and progression. These findings support a link between antiviral immune responses and MS pathophysiology and offer a promising blood-based autoantibody signature that could inform future diagnostic and therapeutic strategies.

neuroscience↗

bioRxiv2022

Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System

The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P [≤] 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research. Significance StatementCoronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, has emerged as a global pandemic with a high morbidity rate and multiorgan complications. It is observed that the host immune system contributes to the varied responses to COVID-19 pathogenesis. Autoantibodies, immune system proteins that mistakenly target the bodys own tissue, may underlie some of this variation. We screened total IgG autoantibody responses against 1,318 human proteins in two COVID-19 patient cohorts. We observed several novel markers in COVID-19 patients that are associated with male fertility, such as sperm protein SPANXN4, STK25, and the apoptotic factor ATF4. Particularly, elevated levels of autoantibodies against the testicular tissue-specific protein SPANXN4 offer significant evidence of anticipating the protein role in COVID-19 associated male reproductive complications.

immunology↗