Journal-Based CME: T- and B-cell Abnormalities, Pneumocystis Pneumonia and Chronic Lymphocytic Leukemia Associated with an AIOLOS Defect in Patients

This Journal-Based CME activity consists of a full-text article that is free to read, a multiple-choice question test, and an evaluation/self-assessment. Learners are tested on their comprehension of the key concepts, with the objective of enriching their clinical practice and patient care through better understanding of scientific advances and new techniques in the fields covered by Journal of Experimental Medicine (JEM).

Questions for this complimentary, online-only activity have been designed by JEM editors in collaboration with the article authors. Each CME activity should take approximately 1 hour to complete.

The article selected for this activity is T- and B-cell abnormalities, pneumocystis pneumonia and chronic lymphocytic leukemia associated with an AIOLOS defect in patients by Sergio D. Rosenzweig, Chief of the Immunology Service at the Clinical Center in the National Institutes of Health, and colleagues.

Article Abstract

AIOLOS/IKZF3 is a member of the IKAROS family of transcription factors. IKAROS/IKZF1 mutations have been previously associated with different forms of primary immunodeficiency. Here we describe a novel combined immunodeficiency due to an IKZF3 mutation in a family presenting with T and B cell involvement, Pneumocystis jirovecii pneumonia, and/or chronic lymphocytic leukemia. Patients carrying the AIOLOS p.N160S heterozygous variant displayed impaired humoral responses, abnormal B cell development (high percentage of CD21low B cells and negative CD23 expression), and abrogated CD40 responses. Naive T cells were increased, T cell differentiation was abnormal, and CD40L expression was dysregulated. In vitro studies demonstrated that the mutant protein failed DNA binding and pericentromeric targeting. The mutant was fully penetrant and had a dominant-negative effect over WT AIOLOS but not WT IKAROS. The human immunophenotype was recapitulated in a murine model carrying the corresponding human mutation. As demonstrated here, AIOLOS plays a key role in T and B cell development in humans, and the particular gene variant described is strongly associated with immunodeficiency and likely malignancy.

About Journal of Experimental Medicine (JEM) and CME Activities

JEM publishes peer-reviewed papers within the field of medical biology, providing novel conceptual insights into immunology, cancer biology, neuroscience, inflammation, vascular biology, microbial pathogenesis, and stem cell biology. These studies range from original findings on all aspects of disease pathogenesis to novel therapeutic approaches. Articles designated for Journal-Based CME have been selected by JEM editors for their clinical relevance and ability to address practice-based gaps.

Select the 'Course Content' tab at the top of this page in order to access the full article and claim CME credit.

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Memorial Sloan Kettering Cancer Center, the Journal of Experimental Medicine (JEM) and Rockefeller University Press. Memorial Sloan Kettering Cancer Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

AMA Credit Designation Statement

Memorial Sloan Kettering Cancer Center designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Recorded/Review Date: October 24, 2024 | Original Release Date: October 25, 2021 | Termination Date: October 25, 2027