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A. Introduction [1,2] navigator

  1. Also called Autoimmune Lymphadenopathy Syndrome (AILD)
  2. Originally called "Canale-Smith Syndrome"
  3. Original description in 1967 in children with severe lymphadenopathy
  4. Mouse strains called "lpr" (Lymphoproliferative) mimic human syndrome

B. Pathogenesis navigator

  1. Most types due to mutations in the apoptosis inducing gene Fas (CD95, Apo1) [2,3]
  2. Classification of APLS [5]
    1. Type 0: homozygous Fas mutations lead to complete deficiency of Fas protein; severe form
    2. Type Ia: heterozygous Fas mutations, partial apoptosis defects
    3. Type Ib: heterozygous Fas ligand mutations, partial apoptosis defects
    4. Type II: resistance to Fas-mediated apoptosis, due to caspase 10 mutations
    5. Type III: normal apoptosis in vitro; most cases due to somatic heterozygous Fas mutations [5]
  3. Abnormalities in apoptosis causes non-malignant accumulation of lymphocytes
  4. These are atypical T lymphocytes (CD3+ but CD4- and CD8-) and may be inert
  5. B cell dysregulation is very common but cell numbers only slightly increased
  6. Most Fas mutations appear to affect the Fas-"Death Domain" [4]
  7. Combined Fas and perforin mutations in patient with APLS and non-Hodgkin lymphoma [6]

C. Lymph Node Analysis navigator

  1. Massive lymphadenopathy
  2. Preserved architecture; follicular hyperplasia paracortical expansion
  3. May be confused with immunoblastic lyphoma
  4. Many paracortical cells express Ki-67 proliferation associated antigen
  5. Frank lymphoma may be present

D. Common Symptomsnavigator

  1. Lymphadenopathy is major symptom
  2. Hypergammaglobulinemia
  3. Splenomegaly / Hepatomegaly
  4. Autoimmune disease is very common, increasing over time
  5. May have increased risk for infection
  6. Overall associated with increased lymphoma risk [6]

E. Autoimmune Hematologic Diseasesnavigator

  1. Not uncommon
  2. Autoimmune neutropenia
    1. Infectious risk may increase substantially
    2. Recombinant G-CSF may be useful (though counterintuitive)
  3. Autoimmune hemolytic anemia
  4. Autoimmune thrombocytopenia
    1. Glucocorticoids usually effective
    2. Intravenous immune globulin usually transiently effective
    3. Cyclosporine may add benefit

References navigator

  1. Straus SE, Sneller M, Lenardo MJ, et al. 1999. Ann Intern Med. 130(7):591 abstract
  2. Rieux-Laucat F, Le Diest F, Hivrost C, et al. 1995. Science. 268:1347 abstract
  3. Le Diest, F., Emile JF, Rieux-Laucat F, et al. 1996. Lancet. 348:719 abstract
  4. Drappa J, Vaishnaw AK, Sullivan KE, et al. 1996. NEJM. 335(22):1643 abstract
  5. Holzelova E, Vonarbourg C, Stolzenberg MC, et al. 2004. NEJM. 351(14):1409 abstract
  6. Clementi R, Dagna L, Dianzani U, et al. 2004. NEJM. 351(14):1419 abstract