ANA positivity and complement level in pleural fluid are potential diagnostic markers in discriminating lupus pleuritis from pleural effusion of other aetiologies

Abstract

Objective: Lupus pleuritis is the most common pulmonary manifestation of systemic lupus erythematosus (SLE). We aimed to compare various biomarkers in discriminating between pleural effusions due to lupus pleuritis and other aetiologies.

Methods: We determined in 59 patients (16 patients with SLE and 43 patients without SLE) pleural fluid levels of high-mobility group box 1, soluble receptor for advanced glycation end products (sRAGE), adenosine deaminase (ADA), interleukin (IL) 17A, tumour necrosis factor-α, antinuclear antibodies (ANA), and complements C3 and C4.

Results: We found significant differences in the pleural fluid level of sRAGE, ADA, IL-17A, C3 and C4, and in the proportion of ANA positivity, among lupus pleuritis and other groups with pleural effusion. Specifically, ANA positivity (titre ≥1: 80) achieved a high sensitivity of 91%, specificity of 83% and negative predictive value (NPV) of 97% in discriminating lupus pleuritis from non-lupus pleural effusion. A parallel combination of the level of C3 (<24 mg/dL) and C4 (<3 mg/dL) achieved a sensitivity of 82%, specificity of 89% and NPV of 93% in discriminating lupus pleuritis from non-lupus exudative pleural effusion.

Conclusions: In conclusion, ANA, C3 and C4 in pleural fluid are useful in discriminating lupus pleuritis from pleural effusion due to other aetiologies with high NPV.

Keywords: autoantibodies; autoimmune diseases; cytokines; inflammation; systemic lupus erythematosus.

Figure 1

Pleural fluid level of potential biomarkers, including (A) HMGB1, (B) sRAGE, (C) ADA activity, (D) IL-17A, (E) TNF-alpha, (F) C3, and (G) C4. ADA, adenosine deaminase; HMGB1, high-mobility group box 1; IL-17A, interleukin 17A; sRAGE, soluble receptor for advanced glycation end products; TNF-α, tumour necrosis factor-α.

Figure 2

Receiver operating characteristic curve for pleural fluid level of potential biomarkers with respect to (a) lupus pleuritis vs. infection-related pleural effusion, (b) lupus pleuritis vs. malignant pleural effusion, and (c) lupus pleuritis vs. fluid overload. One patient without SLE with malignant pleural effusion did not undergo C3 level determination. One patient without SLE and with malignant pleural effusion, and one without SLE and with fluid overload did not undergo C4 level examination. One patient without SLE and with infection-related pleural effusion did not undergo ADA activity examination. ADA, adenosine deaminase; AUC, area under the receiver operating characteristic curve; IL-17A, interleukin 17A; sRAGE, soluble receptor for advanced glycation end products.