[Lymphoproliferative disorders and inborn errors of immunity]

Area of Science:

• Immunology
• Genetics
• Oncology

Background:

• Lymphoproliferative disease (LPD) is a spectrum of conditions from lymphadenopathy to lymphoma.
• LPD frequently associates with Epstein-Barr virus (EBV) infections, inborn errors of immunity (IEI), and post-transplant settings.
• Severe combined immunodeficiency and X-linked lymphoproliferative disease often manifest as LPD.

Purpose of the Study:

• To review the landscape of lymphoproliferative diseases (LPD).
• To highlight the association of LPD with Epstein-Barr virus (EBV) and inborn errors of immunity (IEI).
• To discuss genetic underpinnings of specific LPDs like Autoimmune Lymphoproliferative Syndrome (ALPS).

Main Methods:

• Literature review of lymphoproliferative disorders.
• Analysis of genetic mutations associated with LPD and EBV infection.
• Clinical condition assessment in patients with inborn errors of immunity.

Main Results:

• Autoimmune lymphoproliferative syndrome (ALPS) results from germline mutations in apoptosis pathway genes (FAS, FASL, CASP10, CASP8, FADD).
• ALPS is characterized by autoimmune diseases and LPD manifestations like hepatosplenomegaly and lymphadenopathy.
• Genetic defects in genes like SH2D1A, XIAP, and others predispose individuals to EBV-associated LPD in IEI patients.

Conclusions:

• LPD is a diverse group of diseases with significant ties to EBV and immune system dysfunction.
• Understanding the genetic basis of LPD, including ALPS and EBV-associated forms, is crucial for patient management.
• Prompt recognition of EBV-associated LPD in IEI patients is clinically important.