Frontiers in Medicine (Nov 2022)

BLNK mutation associated with T-cell LGL leukemia and autoimmune diseases: Case report in hematology

  • Guillemette Fouquet,
  • Guillemette Fouquet,
  • Guillemette Fouquet,
  • Julien Rossignol,
  • Laure Ricard,
  • Flavia Guillem,
  • Flavia Guillem,
  • Lucile Couronné,
  • Vahid Asnafi,
  • Manon Vavasseur,
  • Mélanie Parisot,
  • Nicolas Garcelon,
  • Frédéric Rieux-Laucat,
  • Arsène Mekinian,
  • Arsène Mekinian,
  • Olivier Hermine,
  • Olivier Hermine,
  • Olivier Hermine

DOI
https://doi.org/10.3389/fmed.2022.997161
Journal volume & issue
Vol. 9

Abstract

Read online

We present the case of a female patient with a heterozygous somatic BLNK mutation, a T-cell LGL (large granular lymphocyte) leukemia, and multiple autoimmune diseases. Although this mutation seems uncommon especially in this kind of clinical observation, it could represent a new mechanism for autoimmune diseases associated with LGL leukemia. The patient developed several autoimmune diseases: pure red blood cell apalsia, thyroiditis, oophoritis, and alopecia areata. She also presented a T-cell LGL leukemia which required treatment with corticosteroids and cyclophosphamide, with good efficacy. Interestingly, she had no notable infectious history. The erythroblastopenia also resolved, the alopecia evolves by flare-ups, and the patient is still under hormonal supplementation for thyroiditis and oophoritis. We wanted to try to understand the unusual clinical picture presented by this patient. We therefore performed whole-genome sequencing, identifying a heterozygous somatic BLNK mutation. Her total gamma globulin level was slightly decreased. Regarding the lymphocyte subpopulations, she presented a B-cell deficiency with increased autoreactive B-cells and a CD4+ and Treg deficiency. This B-cell deficiency persisted after complete remission of erythroblastopenia and LGL leukemia. We propose that the persistent B-cell deficiency linked to the BLNK mutation can explain her clinical phenotype.

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