Volume 11 • Number 3 • September 2024

Review

Vol. 11No. 3pp. 45–66
The COVID-19 pandemic, driven by SARS-CoV-2, has seen the emergence of multiple variants, complicating public health responses and vaccine development. Individuals with primary immunodeficiency (PID) are particularly vulnerable to severe COVID-19. This review examines the heightened risk and varied clinical outcomes in patients with PID, exploring the role of immunoglobulin replacement therapy which provides passive immunity through anti-SARS-CoV-2 antibodies. During the Omicron variant surge, this cohort of patients generally experienced less severe illness and higher survival rates compared to earlier waves. Yet, immunocompromised individuals and those with PID should continue to remain cautious to minimize exposure. The review underscores the importance of vigilant public health measures, targeted interventions, and tailored vaccination strategies to protect PID patients as COVID-19 transitions to an endemic phase. Ongoing research is essential to fully understand COVID-19's long-term impact on immunocompromised individuals and to refine their clinical management.

Original Article

Vol. 11No. 3pp. 67–72
Background: The human signal transducer and activator of transcription 1 (STAT1) is a latent cytoplasmic transcription factor and one of seven members of the STAT family. Autosomal dominant (AD) STAT1 gain-of-function (GOF), characterized by enhanced phosphorylation of the tyrosine-701 residue and STAT1 activation, is commonly associated with chronic mucocutaneous candidiasis (CMCC), immunodeficiency, aneurysms, malignancies, and autoimmune phenomena.The best management strategies for patients with STAT1 GOF remain unclear. Typically, the standard care includes supportive treatments such as antimicrobial prophylaxis, either alone or combined with immunoglobulin replacement therapy. Biological therapies such as JAK inhibitors have been shown to alleviate symptoms of infection and autoimmune disorders in patients with STAT1 GOF mutations. However, there is a lack of long-term outcome data for JAK inhibition. Hematopoietic stem cell transplantation (HSCT) is an alternative treatment option for a subset who experience a persistent disease course despite conventional therapy. However, the effectiveness of HSCT for this condition is not yet well established.Methods: Our patient’s medical records were analyzed retrospectively, including her medical history.Results: We present the outcome of HSCT performed on a 27-year-old female with STAT1 GOF, conducted as a treatment for acute myeloid leukemia (AML).Conclusion: HSCT may serve as an alternative and potentially curative treatment for certain STAT1 GOF patients with progressive, life-threatening conditions that do not respond to conventional therapies. Additional research is needed to improve the management of these patients.Statement of Novelty: We present a novel case study of HSCT as a treatment for AML in a 27-year-old patient with STAT1 GOF, highlighting the potential for curative outcomes in progressive, life-threatening conditions unresponsive to conventional therapies. This case contributes to the limited body of evidence supporting the efficacy and challenges of HSCT in STAT1 GOF patients.

Novel Mutation and VUS

Vol. 11No. 3pp. 73–77
Introduction: Agammaglobulinemia is a primary immunodeficiency characterized by absent B cells and originates from X-linked or autosomal mutations affecting B cell maturation. While the most common agammaglobulinemia is X-linked, one well-documented site of autosomal recessive agammaglobulinemia is within the immunoglobulin μ heavy chain protein, encoded by the IGHM gene. Such variants frequently result in clinical presentations of recurrent bacterial infections early in life.Aim: To describe a case of a five-year-old female with agammaglobulinemia resulting from a novel homozygous IGHM variant, presenting with pneumonia complicated by empyema and H. influenzae bacteremia.Methods: Case data was compiled retrospectively from the patient’s medical chart, including relevant laboratory testing for immunoglobulins, quantitative B cell subsets, and genetic testing using a primary immunodeficiency panel.Results: The proband is a 5-year-old female with a history of recurrent pneumonia, presenting with H. influenzae bacteremia in the context of pneumonia complicated by an empyema. Investigations revealed low immunoglobulin levels, absent vaccine responses, and undetectable B cells on flow cytometry. Genetic testing revealed a novel homozygous variant in the IGHM gene: c.775T>C, p.Trp259Arg.Conclusion: Autosomal recessive agammaglobulinemia is a rare but severe, treatable disorder of the immune system which typically presents in early childhood. Hypomorphic mutations, while less commonly reported in the literature, are an important consideration in atypical presentations of primary immunodeficiencies, such as in the case presented.Statement of Novelty: Herein, we report a case of agammaglobulinemia presenting with a novel homozygous variant in the IGHM gene leading to later onset agammaglobulinemia in a 5-year-old female.
List of Issues
Volume 11
Issue 3
September 2024
Volume 11
Issue 2
June 2024
Volume 11
Issue 1
March 2024
Volume 10
Issue 4
December 2023
Volume 10
Issue 3
September 2023
Volume 10
Issue 2
June 2023