What is the role of lab tests in the workup of autoimmune lymphoproliferative syndrome (ALPS)?

Updated: Jul 29, 2019
  • Author: Akaluck Thatayatikom, MD, RhMSUS; Chief Editor: Harumi Jyonouchi, MD  more...
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Answer

Although no single laboratory study is diagnostic of ALPS, several laboratory tests should be obtained.

Autoantibodies are frequently found in patients with ALPS. A study of 79 ALPS patients detected autoantibodies in 81%. [15] The common autoantibodies detected in patients with ALPS is a positive Coombs direct antiglobulin test (DAT) and antiplatelet antibodies. Autoimmune neutropenia with antineutrophil antibody is less common. [42]

A CBC with differential may reveal lymphocytosis, reticulocytosis, thrombocytopenia, anemia, neutropenia, monocytosis, or eosinophilia. A quantitative immunoglobulin panel should be obtained if a diagnosis of ALPS is suspected or confirmed. Hypergammaglobulinemia with high IgG and IgA is a common feature in ALPS. Low IgM can be seen resulting from exacerbated class switching. [1]   

Patients with ALPS characteristically demonstrate elevated DNT cells in the peripheral circulation, bone marrow, spleen, or lymphoid tissues. These lymphocytes may be detected by flow cytometric immunophenotyping of samples from any of these sites. [41]

Most patients with ALPS exhibit defective lymphocyte apoptosis. Although the defect of lymphocyte apoptosis in vitro is one of accessory criteria, the test is not routinely used since it is available at specialized laboratories and somatic FAS mutations can have normal result. [40]

Other abnormal laboratory findings that are commonly found in ALPS patients include elevated soluble FasL levels, elevated transaminases (in the subset of patients with autoimmune hepatitis), elevated plasma IL-10 or IL-18 levels, proteinuria (in patients with glomerulonephritis), and elevated serum levels of vitamin B-12. [43]

Molecular genetic testing should also be obtained in patients with clinical or laboratory features consistent with a diagnosis of ALPS. Specifically, genetic analysis of the FAS receptor gene (TNFRSF6), the FasL gene (TNFSF6) and the caspase 10 gene (CASP-10) is warranted. Mutations of the FAS gene have been identified as the cause of most cases of ALPS. If mutation of FAS is not detected, an analysis of the other genes of ALPS or ALPS-like disorders mutations should be considered. 

This genetic testing is important for the following 2 reasons:

  • If a mutation is identified, genetic counseling must be provided to the family, and other family members must be invited for screening evaluations.
  • The location of the specific gene mutation is important for the prognosis because certain mutation loci are associated with a higher risk of complications, including lymphoma; patients with a mutation of the intracellular domain of FAS have a 14-fold higher risk of non-Hodgkin lymphoma and a 51-fold higher risk of Hodgkin lymphoma. [41]

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