Complement inhibition has shown promise in various disorders, including COVID‐19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement‐related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID‐19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence‐based algorithm to predict disease outcome (ICU vs. non‐ICU admission). A recently introduced alpha‐index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha‐index in ranking a substantial number of genetic variants. This approach enables the implementation of well‐established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs.

Advancements in artificial intelligence (AI) predictive models have emerged as valuable tools for predicting survival outcomes in allogeneic haematopoietic stem cell transplantation (allo‐HSCT). These models primarily focus on pre‐transplant factors, while algorithms incorporating changes in patient's status post‐allo‐HSCT are lacking. The aim of this study was to develop a predictive soft computing model assessing survival outcomes in allo‐HSCT recipients. In this study, we assembled a comprehensive database comprising of 564 consecutive adult patients who underwent allo‐HSCT between 2015 and 2024. Our algorithm selectively considers critical parameters from the database, ranking and evaluating them based on their impact on patient outcomes. By utilising the Data Ensemble Refinement Greedy Algorithm, we developed an AI model with 93.26% accuracy in predicting survivorship status in allo‐HSCT recipients. Our model used only seven parameters, including age, disease, disease phase, creatinine levels at day 2 post‐allo‐HSCT, platelet engraftment, acute graft‐versus‐host disease (GvHD) and chronic GvHD. External validation of our AI model is considered essential. Machine learning algorithms have the potential to improve the prediction of long‐term survival outcomes for patients undergoing allo‐HSCT.

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII. Emerging evidence implicates CD4+ T cell activation in mediating this autoimmune response, with their involvement like that observed in congenital hemophilia A. Several genes such as HLA II DRB*16, DQB1*0502, and CTLA-4 + 49 are responsible for the pathogenesis of AHA. Epigenetic modifications and mainly long-coding RNAS (lncRNAs) are potentially contributing to the pathogenesis of AHA. The treatment approach of AHA includes the management of acute bleeding events and the administration of immunosuppressive medications. This review aimed to summarize the published data on the genetics and epigenetics of AHA. The severity and the mortality of this disease are creating an emerging need for further research in the field of the genetics and epigenetics of acquired hemorrhagic disorder.

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) is considered a rare manifestation of APS. The aim of our case series is to study patients with APS and AN. Methods: A retrospective study was performed on 80 patients diagnosed with APS. Results: AN was observed in 3 patients out of 80 diagnosed with APS. AN of the femoral head was observed in all cases. Case (1): A 54-year-old woman presented due to multiple ischemic infarctions in the brain, as detected in magnetic resonance imaging of the brain, Raynaud’s phenomenon, and AN of the femoral head. In laboratory testing, a prolongation of activated partial thromboplastin time was recorded. A heterozygous mutation was also found in the gene MTHFR C677T, and the patients was positive for lupus anticoagulant (LA). The patient was given clopidogrel and acenocoumarol. Case (2): A 52-year-old man was diagnosed with APS, based on the clinical presentation (stroke) and positivity for LA and anti-β2GPI (anti-β2 glycoprotein I antibody). In his medical history, episodes of vertigo and an episode of AN of the femoral head 2 years ago were described. Case (3): A woman aged 43 years presented due to AN of the femoral head. Due to suspected APS, immunological testing was performed, and positivity for LA and IgM anticardiolipin antibodies was detected. She was treated with acenocoumarol. Conclusions: AN is a rare clinical manifestation of APS, which may precede the diagnosis of APS for many years.