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Identification of Germinal Centres in the Lymph Node of a Patient with Hyperimmunoglobulin M Syndrome Associated with Congenital Rubella

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Abstract

Background

The hyper immunoglobulin M syndrome (HIM) associated with congenital rubella infection (rHIM) is an extremely rare disorder, where patients have elevated serum IgM in association with reduced IgG and IgA. We have previously shown that in contrast to X-linked HIM (XHIM), a patient with well-characterised rHIM is able to express functional CD40 ligand, undergo immunoglobulin isotype switching and to generate memory B cells. Here we describe the ultrastructural features of an excised lymph node from this patient.

Methods

An inguinal lymph node was surgically removed and examined histologically as well as by immunohistochemistry. It was then stained with multiple fluorescent dyes to visualize the cellular interactions within the node. Flow cytometry was undertaken on a cellular suspension from the node.

Findings

Our patient has normal lymph node architecture by light microscopy. Immunohistochemistry studies showed the presence of scattered germinal centres. Polychromatic immunofluorescence staining showed disruption of the architecture with mostly abnormal germinal centres. A small number of relatively intact germinal centres were identified. Both IgM and IgG bearing cells were identified in germinal centres.

Interpretation

In contrast to XHIM where germinal centres are absent, the presence of small numbers of relatively normal germinal centres explain our previous identification of isotype switched memory B cells in rHIM.

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Abbreviations

CRS:

Congenital rubella syndrome

FDC:

Follicular dendritic cells

HIM:

Hyper Immunoglobulin M Syndrome

rHIM:

Hyper immunoglobulin M syndrome associated with congenital rubella infection

XHIM:

X-linked hyperimmunoglobulin M syndrome

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Acknowledgments

We are very grateful to the patient for consenting to publication of these diagnostic studies, for the benefit of others. We thank the A + Trust and LabPlus management for supporting immune deficiency research. We thank Drs Kitty Croxson, Richard Steele, Shannon Brothers, Bill Abbott and Anthony Jordan for helpful discussions. We thank Danny Lim for the B cell memory and lymph node flow cytometry studies.

Funding

This diagnostic study was internally funded.

Author information

Authors and Affiliations

  1. Departments of Virology and Immunology, LabPlus, Auckland Hospital, Park Rd, Auckland, New Zealand

    Rohan Ameratunga, Wikke Koopmans, Maia Brewerton & See-Tarn Woon

  2. Clinical Immunology, Auckland Hospital, Park Rd, Auckland, New Zealand

    Rohan Ameratunga

  3. Department of Histopathology, LabPlus, Auckland City Hospital, Park Rd, Auckland, New Zealand

    Richard Lloydd & Chris van Vliet

  4. Department of Molecular Medicine and Pathology, University of Auckland, Auckland, Park Rd, Auckland, New Zealand

    Rohan Ameratunga & Wikke Koopmans

  5. Maurice Wilkins Centre for Molecular Discovery, University of Auckland, Auckland, New Zealand

    Chun-Jen J. Chen, P. Rod Dunbar & Claudia J. Mansell

  6. School of Biological Sciences, University of Auckland, Auckland, New Zealand

    Chun-Jen J. Chen, P. Rod Dunbar & Claudia J. Mansell

Authors
  1. Rohan Ameratunga
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  2. Chun-Jen J. Chen
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  3. Wikke Koopmans
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  4. P. Rod Dunbar
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  5. Maia Brewerton
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  7. Claudia J. Mansell
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  8. Chris van Vliet
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  9. See-Tarn Woon
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Corresponding author

Correspondence to Rohan Ameratunga.

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Ameratunga, R., Chen, CJ.J., Koopmans, W. et al. Identification of Germinal Centres in the Lymph Node of a Patient with Hyperimmunoglobulin M Syndrome Associated with Congenital Rubella. J Clin Immunol 34, 796–803 (2014). https://doi.org/10.1007/s10875-014-0084-6

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  • DOI: https://doi.org/10.1007/s10875-014-0084-6

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