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Autoantibodies with high avidity and in high concentration are usually detected in sera of patients with Navitoclax cost systemic autoimmune diseases, and indicate tolerance breakdown. The strict association of some autoantibodies with certain diseases has granted them the reputation of specific biomarkers [1], [2], [3], [4]. The identification of a novel autoantibody associated with a given disease may contribute to the understanding of its pathophysiology and may enrich the array of diagnostic tests for that disease [2]. The standard method for autoantibody screening is the indirect immunofluorescence assay on HEp-2 cells (IIF-HEp-2), historically known as the antinuclear antibody ANA test.

However, a positive IIF-HEp-2 test is also observed in some patients with infectious and malignant diseases, as well as in up to 13% of healthy people [4], [5], [6]. A positive IIF-HEp-2 test has been reported in 7 to 50% of patients with HCV [7], [8], [9], [10], [11]. The few studies reporting on the immunofluorescence pattern of IIF-HEp-2 test in HCV patients have emphasized the nuclear fine speckled pattern and cytoplasmic fibrillar pattern [8], [9], [10], [12], [13]. Most IIF-HEp-2 reactivity in HCV patients is not associated with autoantibodies traditionally related to specific autoimmune diseases. However, a small fraction of HCV patients do present well characterized autoantibodies conventionally associated with autoimmune hepatitis, such as anti-LKM and anti-smooth muscle antibodies [14], [15], [16].

Anti-LKM antibody is classically associated with type 2 autoimmune hepatitis, but it has been observed in up to 10% of HCV patients, mostly males, and it appears to indicate mild liver histological and biochemical alterations in these patients [15], [17]. Anecdotal reports suggest that interferon-�� therapy may worsen inflammatory liver activity and increase serum enzyme in LKM-reactive HCV patients [17], [18]. Anti-smooth muscle antibodies are directed mostly to the polymerized form of actin and are traditionally associated with type 1 autoimmune hepatitis, but they can also be observed in a small fraction of HCV patients, usually at a lower titer than in autoimmune hepatitis [16].

HCV patients presenting anti-smooth muscle autoantibodies appear not to differ from those without these autoantibodies concerning clinical profile and response to treatment [15], [19]. Recently a novel IIF-HEp-2 cytoplasmic pattern has been reported in HCV patients [20], [21], [22], [23], [24], [25]. It is characterized by a variable number of 3�C10 ��m long rods and 2�C5 ��m diameter rings spread throughout the cytoplasm. Accordingly, the novel IIF-HEp-2 pattern has been designated the ��rods and rings�� (RR) pattern. Interestingly, not all commercial GSK-3 HEp-2 slides are appropriate for the observation of the RR pattern.