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| ==Laboratory Findings== | | ==Laboratory Findings== |
| * Elevated peripheral blood Double Negative T cells (DNTs)<ref name="pmid12139944">{{cite journal| author=Bleesing JJ, Brown MR, Novicio C, Guarraia D, Dale JK, Straus SE et al.| title=A composite picture of TcR alpha/beta(+) CD4(-)CD8(-) T Cells (alpha/beta-DNTCs) in humans with autoimmune lymphoproliferative syndrome. | journal=Clin Immunol | year= 2002 | volume= 104 | issue= 1 | pages= 21-30 | pmid=12139944 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12139944 }} </ref>
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| ** Required for diagnosis
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| ** Immunophenotype: CD3+/CD4-/CD8-/TCRalpha/beta+
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| ** Measured by [[flow cytometry]]: Normal values <2.5% total T cells; <1% of total lymphocytes in peripheral blood
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| ** Marked elevations >5% virtually pathognomic for ALPS
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| ** Mild elevations also found in other autoimmune diseases
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| ** Thought to be cytotoxic T lymphocytes that have lost CD8 expression
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| ** ?Unknown if driver of disease or epiphenomenon
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| ** May be falsely elevated in setting of lymphopenia or falsely decreased with immunosuppressive treatment
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| * Defective in vitro Fas mediated apoptosis
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| ** Required for diagnosis under old definition. Now can be used to make diagnosis; however, not required to make diagnosis.
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| ** Time and labor intensive assay.
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| ** T cells from patient and normal control supported in culture for >10 days with mitogen stimulation and IL-2 expansion and then exposed to anti-Fas IgM monoclonal antibody
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| ** ALPS patient T cells: Do not die with anti-Fas monoclonal antibody exposure. Normal T cells from unaffected patient do.
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| ** False negative in somatic Fas variant ALPS and FasL variant ALPS
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| * Genetic mutations in ALPS causative genes (see below)
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| * Biomarkers<ref name="pmid19176318">{{cite journal| author=Magerus-Chatinet A, Stolzenberg MC, Loffredo MS, Neven B, Schaffner C, Ducrot N et al.| title=FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function. | journal=Blood | year= 2009 | volume= 113 | issue= 13 | pages= 3027-30 | pmid=19176318 | doi=10.1182/blood-2008-09-179630 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19176318 }} </ref> <ref name="pmid20227752">{{cite journal| author=Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S et al.| title=Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. | journal=J Allergy Clin Immunol | year= 2010 | volume= 125 | issue= 4 | pages= 946-949.e6 | pmid=20227752 | doi=10.1016/j.jaci.2009.12.983 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20227752 }} </ref>
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| ** Polyclonal [[hypergammaglobulinemia]]<ref name="pmid20068224">{{cite journal| author=Seif AE, Manno CS, Sheen C, Grupp SA, Teachey DT| title=Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study. | journal=Blood | year= 2010 | volume= 115 | issue= 11 | pages= 2142-5 | pmid=20068224 | doi=10.1182/blood-2009-08-239525 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20068224 }} </ref>
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| ** Elevated serum FASL
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| ** Elevated plasma [[IL-10]] and/or IL-18
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| ** Elevated plasma or serum [[vitamin B12]]
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| * [[Autoantibodies]]: Non-specific. Can have antibodies to blood cells (DAT, anti-neutrophil, anti-platelet). Also, can have positive [[ANA]], [[RF]], [[ANCA]].
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
Editor-In-Chief: Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] David Teachey, MD [2] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S
Overview
An elevated concentration of serum double negative α/β T cells comprising more than 1.5% of the total lymphocytes or at least 2.5% of total T cells along with chronic lymphadenopathy or splenomegaly for more than 6 months are the two required testing for clinical diagnosis of Autoimmune lymphoproliferative syndrome which leads to ancillary testing. Confirmatory testing for ALPS is the testing for the ALPS-related mutations or functional testing of patient T cells are requires according to the 2010 guidelines.
Laboratory Findings
References