Details

Autor(en) / Beteiligte

• Frans, Glynis, MPharm
• Moens, Leen, PhD
• Schaballie, Heidi, MD
• Wuyts, Greet, BSc
• Liston, Adrian, PhD
• Poesen, Koen, MPharm, PhD
• Janssens, Ann, MD, PhD
• Rice, Gillian I., PhD
• Crow, Yanick J., MD, PhD
• Meyts, Isabelle, MD, PhD
• Bossuyt, Xavier, MD, PhD

Titel

Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood

Ist Teil von

• Journal of allergy and clinical immunology, 2017-01, Vol.139 (1), p.360-363.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Allogenic hematopoietic stem cell transplantation was curative in 1 patient.1,2 TRNT1 is an enzyme necessary for tRNA aminoacylation by adding 2 cytosine-and 1 adenosine-residues (CCA) to the 3' end of mitochondrial and cytosolic tRNA molecules.3 Disease-causing mutations lead to a reduction in CCA-adding activity, defective mitochondrial translation, and impaired clearance of tRNAs with backbone damage.4 The loss of TRNT1-dependent quality-control mechanisms leads to an impaired intracellular stress response.3 Here, we report a patient with a homozygous TRNT1 mutation and progressive B-cell immunodeficiency. Laboratory parameter Sample Normal values Patient Mother Father 18 y 22 y 23 y 51 y 52 y Immunoglobulins[low *] IgG (g/L) 9.15 11.20 9.91 9.16 11.3 7.51-15.60 IgG1 (g/L) 5.42 6.60 -- -- -- 4.90-11.40 IgG2 (g/L) 3.41 3.58 -- -- -- 1.50-6.40 IgG3 (g/L) 0.24 0.11 -- -- -- 0.20-1.10 IgG4 (g/L) 0.45 0.12 -- -- -- 0.08-1.40 IgA (g/L) 0.14 0.09 0.09 0.81 2.27 0.82-4.53 IgM (g/L) 0.78 0.40 0.35 1.12 0.80 0.46-3.04 IgE (kU/L) 4 <2 <2 -- -- <=114 Total lymphocytes (109 cells/L) 1.169 1.221 1.142 2.830 1.940 1.208-3.586 CD19+ (109 cells/L) 0.094 0.067 0.055 0.394 0.196 0.082- 0.476 B-cell memory subsets (% of CD19+) CD27+IgM+IgD+ -- 13.4 -- 15.9 2.8 7.4-13.9[dagger] CD27+IgM-IgD- -- 10.1 -- 26.7 30.9 7.2-12.7[dagger] CD27-IgM+IgD+ -- 63.3 -- 48.7 40.5 65.6-79.6[dagger] CD24++CD38++ -- -- 1.5 4.6 4.2 3.0-5.9[dagger] CD24-CD38++ -- -- 0.1 0.3 1.3 0.6-1.6[dagger] Total CD3+ (109 cells/L) 0.904 1.145 1.072 2.056 1.177 0.798-2.823 CD3+CD4+ (109 cells/L) 0.617 0.836 0.774 1.609 0.781 0.455-1.885 CD3+CD8+ (109 cells/L) 0.298 0.296 0.277 0.384 0.360 0.219-1.124 T-cell subsets (% of CD3+ cells) Treg CD4+CD24+CD127- 8.1 -- 9.6 -- -- 5.0-12.0 αβ-TCR cells 98.4 99.3 99.2 -- -- >=90.0 γδ-TCR cells 1.2 0.5 0.6 -- -- <=10.0 CD4+ T-cell subsets (% of CD4+) CD45RA+ 63.1 64.3 57.9 -- -- 32.0-73.0 CD3+CD4+CD45RO+CXCR5+[double dagger] -- -- 4.56 -- -- 2.31-7.54 CD4+ T-cell subsets (% of CD4+CD45RA-) TH1 (IFN-γ) -- -- 5.77 -- -- 1.01-7.27 TH17 (IL-17A) -- -- 0.56 -- -- 0.38-0.81 CD3-CD16+/CD56+ 109 cells/L 0.109 0.004 0.013 0.370 0.559 0.066-0.745 CD56dim (% of CD3-CD56+) -- -- 27.7 96.2 98.3 61.7-98.3§ CD56bright (% of CD3-CD56+) -- -- 72.2 3.8 1.6 0.6-38.3§ Isohemagglutinin titers Anti-A IgG 1/8 -- -- -- -- >1/16 Anti-A IgM 1/8 -- -- -- -- >1/16 Anti-B IgG 1/8 -- -- -- -- >1/16 Anti-B IgM 1/16 -- -- -- -- >1/16 Lymphocyte proliferative response index Tetanus toxoid 200.58 -- 148.33 -- -- >=8.71 PHA 250.40 -- -- -- -- >=45.71 Concanavalin A 379.47 -- -- -- -- >=89.13 Table E1 Laboratory evaluation of immunoglobulin levels, lymphocyte subsets, and lymphoproliferation Abnormal values are indicated in boldface.