Antibody Deficiency in Patients with Biallelic KARS1 Mutations
Francesco Saettini1, Fabiola Guerra2,3, Grazia Fazio4
1Centro Tettamanti, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy. f.saettini@gmail.com.
Journal of Clinical Immunology
|September 28, 2023
Summary
Biallelic KARS1 mutations cause rare KARS-related diseases affecting the nervous system and organs. This study reveals impaired B cell metabolism and frequent immune deficiencies in affected patients.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- KARS1 mutations cause rare KARS-related diseases with multi-systemic manifestations.
- KARS1 encodes lysine-tRNA synthetase, crucial for various cellular functions.
- Immune-hematological abnormalities in KARS-related diseases are under-documented, with no prior functional studies on B cells.
Purpose of the Study:
- To describe a patient with KARS-related disease and immune deficiency.
- To investigate the impact of KARS1 mutations on B cell metabolism.
- To collate and analyze clinical and immunological data from all reported KARS-related disease cases.
Main Methods:
- Clinical and genetic analysis of a novel patient.
- Functional assessment of B cell mitochondrial function.
- Systematic literature review and data collection from published KARS-related disease cases.
Main Results:
- A patient presented with developmental delay, deafness, encephalomyelitis, hypogammaglobulinemia, and recurrent infections due to biallelic KARS1 variants (Phe291Val/Pro499Leu).
- Impaired B cell metabolism, including reduced mitochondrial activity, was observed.
- Analysis of 17 KARS-related disease patients revealed frequent recurrent infections (9/17) and B cell abnormalities (3/9 B cell lymphopenia, 6/15 hypogammaglobulinemia, 4/7 impaired vaccine response).
Conclusions:
- KARS1 mutations are associated with significant immune deficiencies, particularly affecting B cells.
- Comprehensive immunological assessment is crucial for patients with KARS-related diseases.
- These patients may benefit from specific supportive treatments, including immunoglobulin replacement therapy.
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