Autoimmune lymphoproliferative syndrome pathophysiology

Editor-In-Chief: David Teachey, MD [1] Sharmi Biswas, M.B.B.S

Autoimmune lymphoproliferative syndrome(ALPS) is the first disease in human beings which are caused by apoptosis defect. Defect in FAS signaling cause benign chronic lymphoproliferation followed by accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. FAS also prevent the mailgnant proliferation of lymphocytes , so ALPS patients are at higher risk of developing lymphoma.There is an identified genetic defect in 2/3 rd of the total cases of ALPS. Germline mutation is the most common type. Somatic mutation, mutations in the proteins of FAS ligand(FASL) and caspase are also responsible in some cases.The pathogenesis of ALPS is still not very clear and research is ongoing.

• Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic.^[1]
  • Autoimmune Hemolytic Anemia
  • Autoimmune Neutropenia
  • Autoimmune Thrombocytopenia
• Other: Can affect any organ system similar to systemic lupus erythematosis (most rare affecting <5% of patients)
  • Nervous: Autoimmune cerebellar ataxia; Guillain-Barre; Transverse myelitis
  • GI: Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis
  • Derm: Urticaria
  • Pulmonary: Bronchiolitis obliterans
  • Renal: Autoimmune glomerulonephritis, nephrotic syndrome
• Cancer: Secondary neoplasms affect approximately 10% of patients. True prevalence unknown as <20 reported cases of cancer. Most common EBER+ Non-Hodgkin’s and Hodgkin’s lymphoma

Histopathological study findings can be helpful to diagnose Autoimmune lymphoproliferative syndrome. The findings are

• Paracortical expansion with infiltration of polyclonal TCR α/β+ DNT cells.^[2]
• DNT cells express TIA-1 and CD57, CD45RO negative
• Follicular hyperplasia
• Polyclonal plasmacytosis
• Spleen has expanded T cell areas dominated by DNT cells.