Lupus Nephritis Patient With Persistent Negative Antinuclear Antibody Hep-2 Test

Abstract

BACKGROUNDSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical course and multiple manifestations. Lupus nephritis (LN) is described in 25 to 50% of patients and is correlated with a worse prognosis. Antinuclear antibodies (ANA) are a hallmark of the disease and are detected in approximately 95% of SLE patients. The association of ANA (such as anti-DNA or antinucleosome) with active LN is well described. A positive immunofluorescence assay on HEp-2 cells (ANA HEp-2 test) is useful for diagnosis and according to the recent EULAR/ACR classification is mandatory for a correct classification of SLE. Besides that, some patients could present SLE including LN without a positive ANA HEp-2 test. CASE REPORTFemale, 38 years old, with diagnosis of SLE in 2015 with oral ulcers, nonscarring alopecia, arthritis, anemia of chronic disease, leukopenia, lymphopenia, complement consumption but with a negative ANA HEp-2 test. She was under treatment with hydroxychloroquine 400 mg/day and remained in clinical remission until February 2021, when she was referred to our service for investigation of lupus flare presenting lower limb edema, mild pericardial effusion, mild bilateral pleural effusion, moderate ascites, hypoalbuminemia, hematuria and proteinuria 10 g/24 h. We repeated ANA HEp-2 test that was also negative. In addition, anti-DNA, anti-Sm, anti-RNP, anti-La/SSB were negative but anti-Ro/SS-A was positive. Renal biopsy revealed diffuse proliferative lupus glomerulonephritis with expressive activity, class IV (A), which closes the hypothesis of nephrotic syndrome secondary to LN. After confirmation of LN, we performed pulse therapy with methylprednisolone 500 mg intravenously for 3 days and cyclophosphamide, with a partial response in decreasing in more than 50% the 24 h protein after a 3-month period. CONCLUSIONANA HEp-2 test presents a high sensitivity for SLE diagnosis with a high negative predictive value. In rare situations, SLE patients can present severe manifestations such as LN, even with a negative ANA HEp-2 test. The requirement of a positive ANA HEp-2 test may, under special conditions, fail to classify patients with a poor prognosis, as occurred in the case described by us.