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Is the ANA test in indirect immunofluorescence (IIF) always positive in the workup of systemic rheumatic disease?

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Is the ANA test in indirect immunofluorescence (IIF) always positive in the workup of systemic rheumatic disease?

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IIF on HEp-2 cells is a preferred screening method for detecting autoantibodies in human sera due to its high sensitivity. However, given the apparent low levels of some autoantigens in the cell substrate, such as the SSA/Ro and Jo-1, the test may show a negative result even when these antibodies are present. Therefore, if clinical findings are highly suggestive for polymyositis, Sjögren’s syndrome or congenital heart block, search for specific autoantibodies by ordering an ENA profile is recommended even if the ANA result was negative.

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