A case of aberrant CD8 T cell–restricted IL-7 signaling with a Janus kinase 3 defect–associated atypical severe combined immunodeficiency

Khanolkar, Aaruni; Wilks, Jeffrey D.; Liu, Guorong; Simpson, B.; Caparelli, Edward; Kirschmann, Dawn A.; Bergerson, Jenna; Fuleihan, Ramsay

doi:10.1007/s12026-020-09123-x

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Its role in maintaining a CD8 + T-cell population has been shown as crucial, potentially contributing to the patient’s CD8 negative status [ 24 – 26 ]. Impaired IL-7 signalling has been linked to atypical JAK3-SCID with preserved NK cell production and impaired T cell function [ 12 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Omenn Syndrome in Two Infants with Different Hypomorphic Variants in Janus Kinase 3

Tsilifis,

Spegarova,

Good

et al. 2024

J Clin Immunol

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Biallelic null or hypomorphic variants in JAK3 cause SCID and less frequently Omenn syndrome. We investigated homozygous hypomorphic JAK3 mutations in two patients, and expression and function of a novel JAK3R431P variant in Omenn syndrome. Immunophenotyping of PBMC from the patient with the novel JAK3R431P variant was undertaken, by flow cytometry and Phosflow after stimulation with IL-2, IL-7, and IL-15. JAK3 expression was investigated by Western blotting. We report two patients with homozygous hypomorphic JAK3 variants and clinical features of Omenn syndrome. One patient had a previously described JAK3R775H variant, and the second had a novel JAK3R431P variant. One patient with a novel JAK3R431P variant had normal expression of JAK3 in immortalised EBV-LCL cells but reduced phosphorylation of STAT5 after stimulation with IL-2, IL-7, and IL-15 consistent with impaired kinase activity. These results suggest the JAK3R431P variant to be hypomorphic. Both patients are alive and well after allogeneic haematopoietic stem cell transplantation. They have full donor chimerism, restitution of thymopoiesis and development of appropriate antibody responses following vaccination. We expand the phenotype of hypomorphic JAK3 deficiency and demonstrate the importance of functional testing of novel variants in disease-causing genes.

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Section: Discussionmentioning

confidence: 99%

Omenn Syndrome in Two Infants with Different Hypomorphic Variants in Janus Kinase 3

Tsilifis,

Spegarova,

Good

et al. 2024

J Clin Immunol

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Diplomate in Medical Laboratory Immunology Certification Examination: A New Chapter for Medical Laboratory Immunology

Khanolkar,

Spiczka,

Bonfield

et al. 2023

ImmunoHorizons

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It is indeed a privilege to be an immunologist in what is arguably the golden age of immunology. From astounding advances in fundamental knowledge to groundbreaking immunotherapeutic offerings, immunology has carved out an enviable niche for itself in basic science and clinical medicine. The need and the vital importance of appropriate education, training, and certification in clinical immunology was recognized by the World Health Organization as far back as 1972. In the United States, Ph.D. scientists with board certification in medical laboratory immunology have served as directors of high-complexity Clinical Laboratory Improvement Amendments– and College of American Pathologists–certified clinical immunology laboratories since 1977. From 1977 to 2017, board certification for medical laboratory immunology was administered by the American Society for Microbiology through the American Board of Medical Laboratory Immunology examination. The American Board of Medical Laboratory Immunology examination was phased out in 2017, and in the fall of 2019, the American Society for Clinical Pathology (ASCP) Board of Certification (BOC) examination committee took on the responsibility of developing a new doctoral-level certification examination for medical laboratory immunology. This transition to the ASCP BOC represents a well-deserved and much-needed recognition of the rapid advances in and the highly specialized nature of medical laboratory immunology and its ever-increasing relevance to patient care. This new ASCP BOC certification is called the Diplomate in Medical Laboratory Immunology, and, as of April 1, 2023, it is now available to potential examinees. In this report, we describe the examination, eligibility routes, and potential career pathways for successful diplomates.

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A case of aberrant CD8 T cell–restricted IL-7 signaling with a Janus kinase 3 defect–associated atypical severe combined immunodeficiency

Cited by 2 publications

References 28 publications

Omenn Syndrome in Two Infants with Different Hypomorphic Variants in Janus Kinase 3

Omenn Syndrome in Two Infants with Different Hypomorphic Variants in Janus Kinase 3

Diplomate in Medical Laboratory Immunology Certification Examination: A New Chapter for Medical Laboratory Immunology

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