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Anti-nuclear antibodies Significance and limitations of test By Hatem H. Eleishi Consultant Rheumatologist In this mini-lecture: What are ANAs How useful they are How unuseful they can be Conclusion What are antinuclear antibodies? Antibodies to nuclear proteins What are nuclear proteins? Nucleolar proteins Ro La dsDNA Smith Proteins that have been synthesized in the nucleus and thereafter where distributed to their respective sites in the cell RNP Jo-1 Scl-70 Ro Nucleosomes Nucleolar proteins Nucleolar Ro La dsDNA Smith Rim RNP Jo-1 Speckled Scl-70 Ro Homogenous Nucleosomes Importance of ANAs One: Serologic hallmarks of patients with systemic autoimmune disease (ANA diseases). Serologic hallmarks of patients with systemic autoimmune disease: • • • • • • • • • • SLE – sensitivity, 99 percent Scleroderma – 97 percent Mixed connective tissue disease – 93 percent Polymyositis/dermatomyositis – 61 percent Rheumatoid arthritis – 52 percent Rheumatoid vasculitis – 33 percent Sjögren's syndrome – 90 percent Drug-induced lupus –100 percent Discoid lupus – 15 percent Pauciarticular juvenile chronic arthritis – 71 percent Two Can provide further diagnostic and prognostic data concerning patients who have minimal symptoms or who have clinical features of more than one autoimmune disease. Examples A young female with: Polyarthralgias Fatigue Malar rash Positive ANA A lupus patient with: Anti-Ro antibodies Limitations of utility and reliability of ANA in diagnosis of systemic autoimmune diseases One: Can also be found in association with: Many autoimmune disorders that are not defined by these antibodies In In Autoimmune disorders that are not defined by and these certain infections otherantibodies: disorders Hashimoto's thyroiditis – 46 percent Chronic infectious diseases: Graves' disease – 50 percent Mononucleosis Autoimmune hepatitis – 71 percent patients receiving certain drugs too. Primary autoimmune cholangitis – 100 Subacute bacterial endocarditis In up to 50 percent of patients taking certain percent Tuberculosis drugs; however, mosthypertension of these patients do Primary pulmonary – 40 Other disorders: not percent develop drug-induced lupus. Some lymphoproliferative diseases. Two: Their presence does not mandate the presence of illness, since they can also be found in otherwise normal individuals. False positive ANAs (ie, ANAs in the absence of autoimmune disease or known antigenic stimuli) are more commonly seen in women and in elderly patients. They are invariably in low titer. Three: Accurate interpretation of different nuclear patterns is confounded several difficulties as: • The recognition of specific patterns is operatordependent, and does not produce a permanent record. The fluorescence fades in one to two days, so that one cannot compare a result with other samples without photographing each test result. • One nuclear pattern may obscure and prevent the recognition of another pattern if several antibodies are present simultaneously. As a result, A positive ANA, although useful and important, yet should be interpreted with caution and within the appropriate clinical setting As a result, A good history compounded with a thorough clinical examination remain to be the mainstay of diagnosis Thank you