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Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that plays a role in DNA repair and replication. Anti-PCNA antibodies are considered a rare but highly specific marker for systemic lupus erythematosus (SLE).1 Anti-PCNA antibodies are reported to occur in approximately 2–6% of patients with SLE.2 3 Given the rare occurrence, however, little is known about the clinical relevance of a positive anti-PCNA test.
To examine whether anti-PCNA antibodies are specifically associated with SLE, we retrospectively identified all patients with anti-PCNA antibodies at the University Hospitals Leuven over a 10-year period (January 1998–December 2007). Patient sera submitted for antinuclear antibody testing were tested by conventional immunofluorescence using Hep2 cells (Immuno Concepts, Sacramento, California, USA). Sera displaying the characteristic fine to coarse speckled nuclear staining of 30–60% interphase cells (fig 1) were considered positive when the titre was 1 : 80 or higher. Anti-PCNA was confirmed by dot blot using commercially available PCNA protein (Diarect, Freiburg, Germany) when enough serum was available (27/29 patients). If there were several anti-PCNA-positive sera from a single patient, only the first serum was included.
During the 10-year period, 51 586 individual patients were tested for the presence of antinuclear antibodies, and 7661 individual patients tested positive. We identified 29 patients with anti-PCNA antibodies (0.4% of antinuclear antibody-positive patients). After approval by the Institutional Review Board, the medical records of all 29 patients were reviewed. Only two patients had SLE (both with glomerulonephritis; meeting the American College of Rheumatology criteria). These patients were diagnosed with SLE 4 and 5 years earlier. Median follow-up for the 27 patients who were not diagnosed with SLE was 2 years. Autoimmune thyroiditis was the most common disorder associated with anti-PCNA antibodies (n = 6). Other immune disorders included polymyalgia rheumatica (n = 2), rheumatoid arthritis (n = 2), autoimmune hepatitis (n = 1), scleroderma (n = 1) and psoriatic arthritis (n = 1). There was one patient with a hepatitis C virus infection (table 1, patient 17), supporting previous reports describing anti-PCNA antibodies in patients infected with hepatitis B or C virus.3
In a second part, we determined the prevalence of anti-PCNA antibodies in an independent cohort of SLE patients followed at the University Hospitals Saint-Luc (Université Catholique de Louvain). Out of 275 patients who met the American College of Rheumatology criteria for the diagnosis of SLE (female/male ratio 92.7%; patients with nephritis 45%), only three (1.1%) had anti-PCNA antibodies (two at diagnosis). Two of them had a juvenile onset and nephritis (one patient had PCNA antibodies at diagnosis, whereas the other patient became positive during the first nephritis relapse). The third patient was PCNA positive at diagnosis but had no nephritis. All three patients had a titre of 1 : 1280 or greater in their first anti-PCNA-positive serum.
In conclusion, the presence of anti-PCNA antibodies has a poor sensitivity for the diagnosis of SLE. Specificity is low, unless high titres (⩾1 : 640) are considered. Positivity for anti-PCNA antibodies in SLE seems to be associated with severe renal involvement as four of the five PCNA-positive patients with SLE had nephritis.
Competing interests None.
Ethics approval Ethics approval was granted by the Institutional Review Board.
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