Presentation and diagnosis of autoimmune lymphoproliferative syndrome (ALPS)

ABSTRACT

Introduction

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of immune dysregulation characterized by derangements in first apoptosis signal-mediated apoptosis and elevations in CD3⁺TCRαβ⁺CD4⁻CD8⁻ ‘double negative’ T cells. As our understanding of this pleomorphic disorder expands, the importance of molecular diagnosis is ever more apparent due to the growing number of disorders that may present with overlapping initial symptoms, but for which there is an ever-increasing list of therapeutic options.

Areas covered

This review will cover the current understanding of the molecular biology and pathophysiology of ALPS as well as describe some of the overlapping syndromes in order to better demonstrate the importance of establishing the correct diagnosis.

Expert opinion

Going forward, international, multicenter collaboration to fully characterize ALPS and the ALPS-like disorders, including with particular focus on defining the defects for those patients with undefined ALPS, is important to both continue to improve our understanding of this disorder and to drive patient care forward to provide the best outcomes. Additionally, it is probably time to re-convene an international expert panel to re-define diagnostic criteria taking into consideration the most recent available data in order to optimize patient care.

KEYWORDS:

• ALPS
• autoimmune lymphoproliferative syndrome
• DNTs
• ALPS-like disorders

Article highlights

• Autoimmune lymphoproliferative syndrome presents in symptomatic individuals in early childhood, although diagnosis is often delayed due to the non-specific nature of the presentation.

• Targeted therapy with mTOR inhibitors corrects the underlying pathobiology in most patients with ALPS but may have intolerable side effects.

• ALPS is a cancer predisposition with increased risk of Hodgkin and non-Hodgkin lymphoma.

• Long-term follow up of treated patients is needed to see if treatment of patients with immunomodulation alters risk of malignancy.

• Molecular diagnosis is critical for patients with suspected ALPS because of the many clinical syndromes with overlapping features that may require different therapeutic approaches.

Disclosure statement

M. Lambert is an advisory board member for Octapharma and Shionogi, a consultant for Amgen, Novartis, Shionogi, Dova, Principia, Argenx, Rigel and Bayer, and has received research funding from Sysmex, Novartis, Rigel, and Astra Zeneca. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.