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Lab Tests (ANA)

ANA 

  1. Nuclear 
    1. Chromatin associated 
        1. (Chromatin is the native histone-DNA complex found in the nucleus of eukaryotic cells, and it is organized into a repeating series of nucleosomes. So, Anti-chromatin ab are also called anti-nucleosome antibody. Anti-DNA antibody are the subset of anti-chromatin antibody Ann Rheum Dis 2003;62:431–434). 
        2. Anti-chromatin (nucleosome) autoantibodies were one of the first autoantibodies ever detected since they make up the majority of antibodies causing LE Cell formation  
        3. Chromatin is composed of 40% DNA, 40% histones and 20% non-histone proteins. Paper has a good diagram 
          1. Reference for 2, 3, Autoimmunity Reviews Volume 7, Issue 8, September 2008, Pages 606-611
      1. DNA
      2. Histone
      3. Centromere (Kinetochore)
      4. Ku
      5. PCNA
      6. DEK
      7. DenseFineSpeckle 70 (DFS70)
    2. Splisosome components
      1. Sm
      2. RNP
    3. Other Ribonuclear proteins 
      1. SSA
      2. SSB
      3. RNA Helicase
      4. TiA 1
      5. Mi 2
      6. p-80 Colin
      7. MA -I
    4. Nucleolar 
      1. RNA Polymerase
      2. Ribosomal RNP
      3. Topoisomerase I (Scl 70)
      4. Topoisomerase II
      5. PM Scl
  2. Cytoplasmic
    1. t-RNA synthetase
      1. Jo1
      2. EJ
      3. OJ
      4. PL7
      5. PL12
      6. KS
      7. MAS
      8. Fodrin
ANA  reflex with comprehensive profile tests10 antibodies highlighted above. It is a  Solid-phase assay  that allows high volume tests. However, will lack the sensitivity of Indirect IFA using Hep-2 cell substrate. While most solid phase assays do not contain antigens found in the nucleolus, the ANA reflex to comprehensive profile used in MCW does test for two nucleolar antibodies as noted above. Because of the lack of sensitivity, ACR recommended that indirect immunofluorescence, using the HEp-2 cell substrate. 

Application: 
High suspicion for CTD or SLE: Order Hep2 cells 
Low suspicion for SLE: Order ANA reflex with comprehensive profile 



Diagram of a nucleosome model
Basically, DNA coils around the histone core


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