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Adenotonsillar pathology in mucopolysaccharidoses – lysosomal storage predominates in paracortical CD63+ cells

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Abstract

Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63. Important, CD63+ storage vacuoles in these cells lacked the monocytes/macrophages lysosomal marker CD68. Such a distinct patterning of CD63 and CD68 was not present in a patient with infantile neurovisceral variant of acid sphingomyelinase deficiency. The CD63+ storage pathology was absent in two MPS I patients who either received enzyme-replacement therapy or underwent hematopoietic stem cells transplantation prior the adenoidectomy. Our study demonstrates novel features of lysosomal storage patterning and suggests diagnostic utility of CD63 detection in adenotonsillar lymphoid tissue of MPS patients.

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Acknowledgements

The authors would like to acknowledge Lenka Kryspinova, Irena Knesplova, and Marie Kolarova for technical assistance. Drs. Pavel Jesina and Stella Mazurova are acknowledged for coordination of tissue sample collection.

Funding

This work was supported by the National Institute for Neurological Research funded by the European Union – Next Generation EU (Program EXCELES, ID Project No. LX22NPO5107), Charles University in Prague (UNCE/MED/007, SVV260516 and Cooperatio), and Ministry of Health of the Czech Republic (RVO-VFN 64165/2012).

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Authors and Affiliations

  1. Department of Otorhinolaryngology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady in Prague, Prague, Czech Republic

    Lenka Murgasova

  2. Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 00, Prague 2, Czech Republic

    Lenka Murgasova, Helena Hulkova, Veronika Baresova, Martin Magner & Jakub Sikora

  3. Institute of Pathology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Helena Hulkova, Jan Stritesky & Jakub Sikora

  4. Department of ENT, 2nd Faculty of Medicine, Charles University and Motol University Hospital in Prague, Prague, Czech Republic

    Michal Jurovcik

  5. Department of Paediatrics, Faculty of Medicine, Comenius University in Bratislava and National Institute of Children‘s Diseases in Bratislava, Bratislava, Slovakia

    Katarina Jurickova

  6. Centre for Inborn Errors of Metabolism, National Institute of Children‘s Diseases in Bratislava, Bratislava, Slovakia

    Katarina Jurickova

Authors
  1. Lenka Murgasova
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  2. Helena Hulkova
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  3. Veronika Baresova
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  4. Michal Jurovcik
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  5. Jan Stritesky
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  6. Katarina Jurickova
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  7. Martin Magner
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  8. Jakub Sikora
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Contributions

LM, MM, and JSi designed the study. LM, HH, JSt, and JSi performed and evaluated morphological studies. LM, MM, KJ, and MJ collected the clinical data and/or performed the surgery. VB facilitated the confocal imaging analyses. LM, MM, and JSi drafted the manuscript and edited the final version of the manuscript. JSi submitted the manuscript. All authors agreed to the submission of the final version of the manuscript.

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Correspondence to Jakub Sikora.

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The authors declare no competing interests.

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Murgasova, L., Hulkova, H., Baresova, V. et al. Adenotonsillar pathology in mucopolysaccharidoses – lysosomal storage predominates in paracortical CD63+ cells. Virchows Arch 484, 135–140 (2024). https://doi.org/10.1007/s00428-023-03662-y

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  • DOI: https://doi.org/10.1007/s00428-023-03662-y

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