Background: X-linked Moesin Associated Immunodeficiency (X-MAID) is a combined immunodeficiency caused by deficiency in the moesin protein. Moesin, which is encoded by the MSN gene, is part of the ezrin-radixin-moesin (ERM) family of transmembrane proteins that interact with the actin cytoskeleton and regulate the shape and migration of cells. Deficiency of moesin is associated with aberrant T cell migration and inadequate immune synapse formation, leading to significant immunodeficiency and recurrent infections. While the clinical presentation of XMAID is diverse, to date, no thymus histopathology findings have been reported. Aim: Describe the thymus histopathology of a patient with X-MAID. Results: Our patient is a 10-year-old male who presented early in life with recurrent infections, dysmorphic features, and severe pulmonary venous stenosis which required a double lung transplant at the age of 4 years. Prior to transplant, he was referred to Immunology for assessment and was subsequently found to harbour a hemizygous variant in the MSN gene (c.278dupT; L93FfsX21). Thymus histophathology findings showed significant cortical atrophy and dysplasia, and was accompanied by reduction in CD3+ cells in the cortex. Abnormally low numbers of suppressor T cells and T helper cells in the thymic cortex and medulla were noted. Conclusion: Thymic findings in X-MAID can include cortical atrophy, dysplasia, and decreased cellularity. This provides further evidence for the importance of moesin on T cell development and migration in the thymus. Statement of Novelty: Description of thymus histopathology in a patient with X-MAID

Background: Due to widespread vaccination efforts worldwide, the mortality rates linked to COVID-19 have been decreasing. Nevertheless, there persists a notable level of morbidity, marked by increased occurrences of post-COVID-19 conditions. This includes the development of new autoimmune and inflammatory diseases in individuals who have recovered from COVID-19. A more severe progression of COVID-19 has been correlated with an increased probability of newly diagnosed autoimmune disease, and among individuals with preexisting autoimmune conditions, COVID-19 increased the risk of developing another autoimmune disease by 23%. Methods: Our patients’ medical records were analyzed retrospectively, including their medical history. Results: We present two cases of primary immunodeficiency patients. One of them experienced the onset of new autoimmune symptoms, while the other had a worsening of her autoimmune condition following COVID-19 infection. Conclusion: Recognizing the potential connection between COVID-19 and autoimmune conditions is crucial for identifying symptoms promptly in primary immunodeficiency patients and ensuring timely treatment. Further research is required to comprehensively grasp the relationship between COVID-19 and the development of autoimmunity in this particular patient group. Statement of Novelty: In this paper, we present a novel exploration into the emergence of autoimmune manifestations in primary immunodeficiency patients subsequent to COVID-19 infection, through an analysis of two distinct case reports.

<b>Introduction: </b> Hyper IgM (HIGM) syndrome is an inborn error of immunity (IEI) that occurs due to defects in immunoglobulin class switch recombination (Ig-CSR). HIGM syndrome typically presents with recurrent infections in early childhood, and is often characterized on investigation with decreased IgG, IgA, and IgE titres, alongside normal or elevated IgM. A common cause of HIGM syndrome is a disruption to the CD40-CD40L interaction that triggers Ig-CSR, of which variants in CD40 are much rarer than in CD40L. We present a case of an 11-year-old female with HIGM syndrome caused by two novel variants of in <i>CD40</i>. <b>Aim:</b> To describe a case report of an eleven-year-old female with HIGM syndrome presenting with recurrent pneumonia. <b>Methods:</b> Data was collected retrospectively from the patient’s medical records. Laboratory investigations included quantitative immunoglobulins, quantitative B and T cell subsets, genetic testing using a primary immunodeficiency panel, and a functional assay for CD40 expression. <b>Results: </b>The proband is an 11-year-old female, who presented with recurrent pneumonia, otitis and septic arthritis. Investigations revealed neutropenia, low IgA, elevated IgM and normal IgG, along with absent vaccine responses. She was identified to harbour two novel variants in CD40: an intronic variant c.52-13A>G p.(?) and a missense variant c.466T>C p.(Ser156Pro). Functional assay indicated low expression of CD40 compared to healthy control, confirming the diagnosis of CD40 deficiency. <b>Conclusion:</b> Class switch defects, such as CD40 deficiency, are rare but significant diagnoses within the spectrum of IEI. This case demonstrates that despite the absence of some clinical red flags for immunodeficiency in infancy, IEIs remain an important consideration in pediatric patients regardless of age. Increasing clinical awareness of IEI will lead to earlier diagnoses, initiation of appropriate treatment, and prevention of potential complications. <b>Statement of Novelty:</b> We describe a patient with a late presentation of hyper IgM syndrome due to two novel variants in the CD40 gene, thus expanding the spectrum of CD40 gene variants.