Diversity in STK4 Deficiency and Review of the Literature.

Abstract: Background Serine-threonine kinase-4 (STK4) deficiency is an autosomal recessive (AR) combined immunodeficiency (CID). Objective We aimed to define characteristic clinical and laboratory features to aid the differential diagnosis and determine the most suitable therapy. Methods In addition to nine patients diagnosed, we reviewed 15 patients from medical literature. We compared B lymphocyte subgroups of our cohort with age-matched healthy controls. Results In our cohort, the median age at symptom onset and age of diagnosis are 6years-8months (mo)(6-248mo) and 7years-5mo (6-260mo), respectively. The main clinical findings were infections (9/9), autoimmune/inflammatory diseases (7/9), and atopy (4/9). CD4 lymphopenia (9/9), lymphopenia (7/9), intermittent eosinophilia (4/9), transient neutropenia (3/9), low immunoglobulin (Ig) M (4/9), and high IgE (4/9) were common. Decreased recent thymic emigrants, naive and central memory T cells, albeit increased effector memory T cells were present. The increase in plasmablasts (p=0.003) and the decrease in switched memory B cells (p=0.022) were significant. Out of a total of 24 patients, cutaneous viral infections (n=20), recurrent pneumonia (n=18), Epstein Barr Virus (EBV)-associated lymphoproliferation (n=11), atopic dermatitis (n=10), autoimmune cytopenia (n=7), and lymphoma (n=6) were frequently seen. Lymphopenia, CD4 lymphopenia, high Ig G, A, and E were the most common laboratory characteristics. Conclusion The differential diagnosis with AR-hyperimmunoglobulin E syndrome is crucial as atopy and CD4 lymphopenia are prominent in both diseases. Immunoglobulins and antibacterial/antiviral prophylaxis are the mainstays of treatment. Clinicians may use immunomodulatory therapies during inflammatory/autoimmune complications. However, more data is needed to recommend hematopoietic stem cell transplantation (HSCT) as a safe therapy.