Is it Autoimmune or NOT! Presented to AONP! October 2015!

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1 Is it Autoimmune or NOT! Presented to AONP! October 2015!

2 Four main jobs of immune system Detects Contains and eliminates Self regulates Protects

3 Innate Immune System! Epithelial cells, phagocytic cells and granulocytes, natural killer lymphocytes, complement proteins Pattern recognition receptors that allow them to recognize pathogens Activates the Adaptive immune system

4 Adaptive Immune system! T and B lymphocytes T cells = immunological memory due to antigen receptors on the lymphocyte surface B cells = secrete immunoglobulins which are major contributors to immune-mediated disease. Failure to resolve an initial immune response produces chronic inflammation, a state of continued innate cell activation and adaptive cell reaction.

5 Autoimmune disease! When the adaptive immune system causes pathology through T cell and B cell mediated effects = Autoimmune disease

6 Where to begin #1 H & P Problem regional or generalized, symmetric or asymmetric, peripheral or central? How did symptoms develop? Inflammation or weakness? Constitutional symptoms? Family history?

7 Labs ESR - sensitive for inflammation but does not distinguish underlying cause CRP - acute phase reactant, but not specific RF - not specific for just RA. Found in other diseases as well. Anti CCP - (anti-citrullinated peptide antibodies) - more specific for RA ANCA - (Antineutrophil Cytoplasmic Antibody) - antibodies that that react to cytoplasmic granules or neutrophils. (test for vasculitis although bx is gold standard) Complement - plasma proteins. In immune mediated diseases a decrease in C 3 and C4 correlate with increased consumption. Not specific for any particular disease.

8 ANA = Antinuclear Antibodies! Autoantibodies develop when T cells and B cells undergo dysregulation.! Most commonly associated disease is SLE. HOWEVER ANA s are found in many other diseases. They are not specific for just SLE.! 98% of people with an ANA may have SLE, but fewer than 10% -30% will fulfill the criteria for a diagnosis of SLE. (criteria in appendix 2)

9 Systemic Rheumatic diseases associated with a +ANA! Drug induced Lupus 100% Mixed connective tissue disease (RNP positivity) 100% SLE up to 100% Scelroderma 80% Pauciarticular juvenile RA 70% Inflammatory myositis 60% Sjorgen s syndrome 50% Rheumatoid arthritis 40%

10 Organ Specific diseases associated with a +ANA! Autoimmune hepatitis 60-90% Thyroid ds (Graves/Hashimoto s thyroiditis) 50% Idiopathic pulmonary hypertension 40% Primary biliary cirrhosis 10-40%

11 Non-autoimmune conditions associated with +ANA! Viral infections - HIV, Hepatitis B or C, EBV Bacterial infections - subacute bacterial endocarditis Myobacterial infection - TB Hematological malignancy - acute myelogenous leukemia Age - 20 to 40% of people over age 65 Healthy individuals - 10 to 30% of the general population Drugs - TNF inhibitors, chloropromazine, hydralazine, isoniazid, methydopa, minocycline, procainamide, quinidine and possibly diphenylhydantoin, penicillamine and gold salts.

12 ANA and beyond! Always order it with reflex. Since antinuclear antibodies react with antigens in the cell nucleus ANA s can be divided into pattern and the nuclear antigen it affects.

13 Extracted Nuclear Autoantibodies! Type! Description! Clinical Association! Anti-dsDNA! Ab to double-stranded DNA! Highly specific for SLE!!! Anti-histone Five types exist SLE, Drug induced SLE, other autoimmune ds.! Anti-ENA! Sm (Smith) RNP (ribonucleoprotein) RNA-protein complexes! Highly specific for SLE! Mixed connective tissue Higher prevalence in African American & Asian!!!! Anti-SSA (Ro)! RNP SLE, especially subacute cutaneous lupus, Neonatal SLE, Sjorgrens!!! Anti-SSB (La) RNP Sjorgren s, SLA, Neonatal SLE

14 Extracted nuclear autoantibodies cont d Type! Description! Clinical Association! Anti-centromere! Anti-Scl 70! Anti-Jo-1! Ab to centromere region of chromosome! Ab to DNA topoisomerase 1! Ab to histidyl trna synthetase! Limited scleroderma, pulmonary HTN, PBC! Diffuse scleroderma, risk of pulmonary fibrosis! Poly/dermatomyositis, Interstitial lung ds, Raynaud s Phenomenon, mechanic s hands, Arthritis. Typically resistant to treatment.!

15 Pharmacotherapy!!

16 !!!! DMARDS! Disease Modifying Anti-Rheumatic Drugs! NSAIDS Hydroxychloroquine Azathioprine Sulfasalazine

17 DMARDS! Corticosteroids Leflunomide Methotrexate

18 ! Biologics! Abatacept Rituximab

19 ! TNF inhibitors! Infliximab Enteracept Adalimumab Golimumab Certrolizumab

20 AND MORE! Tofacitinib Apremilast Usetekinumab Tocilizumab Anakinra

21 resources! Klippel J.H., Stone J.H., Crofford L. J, White P.H. 2008, Primer on rheumatic diseases 13 th ed. Springer: USA Coblyn J.S, Bermas B., Weinblatt M., Helfgott S. 2011, Brigham and women s expert s approach to rheumatology. Jones & Bartlett learning: USA

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