Anti-DFS70 Antibodies: A Useful Biomarker in a Pediatric Case With Suspected Autoimmune Disease

Abstract

Antidense fine speckles 70 (anti-DFS70) antibodies, a peculiar antinuclear antibody (ANA) pattern by indirect immunofluorescence, is frequently observed in ANA-positive individuals with no evidence of systemic autoimmune rheumatic disease. They may be found in many different inflammatory conditions and in healthy individuals. We herein report a case of an 8-year-old girl presenting with generalized edema, hypertension, hepatomegaly, and a history of pharyngitis, which occurred 3 weeks earlier. Laboratory analysis revealed low complement C3 (6 mg/dL), microhematuria, and proteinuria. A diagnosis of acute glomerulonephritis was made. Anti-dsDNA, antiextractable nuclear antigens, and antineutrophil cytoplasmic antibodies were negative. However, a highly positive (1:640) ANA immunofluorescence test with dense fine speckles pattern was found. The presence of anti-DFS70 immunoglobulin G antibodies was confirmed by a specific immunoassay. In conclusion, the presence of isolated anti-DFS70 antibodies may be useful to exclude an autoimmune pathogenesis in those children with a positive ANA test and a clinical picture possibly attributable to systemic autoimmune rheumatic disease. This will avoid further unnecessary investigation with the potential for incorrect diagnosis and possibly harmful treatment.

Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: Preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2

“…This has led to the hypothesis that when they are the sole ANA specificity in the patient's serum, these autoantibodies could be used as exclusion biomarkers of AARD diagnosis in ANA-positive individuals [5,6,11]. This was illustrated in a recent case report of a child with respiratory distress who presented high-titer anti-DFS70/LEDGFp75 autoantibodies as the sole ANA specificity and with no clinical evidence of SARD [50]. In that particular case, these antibodies were used to rule out suspected autoimmune disease, guiding the clinicians to the proper therapeutic intervention [50].…”

“…This was illustrated in a recent case report of a child with respiratory distress who presented high-titer anti-DFS70/LEDGFp75 autoantibodies as the sole ANA specificity and with no clinical evidence of SARD [50]. In that particular case, these antibodies were used to rule out suspected autoimmune disease, guiding the clinicians to the proper therapeutic intervention [50]. …”

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

“…However, a distinctive feature of these antibodies in HI individuals is their relatively elevated frequencies as monospecific antibodies (only ANA detectable in the serum by HEp-2 IIFA), in contrast to patients with SARD in which these antibodies tend to appear concomitantly with other diseaseassociated ANAs [111][112][113]. These observations have led to the hypothesis that monospecific anti-DFS70/LEDGF autoantibodies may be considered as negative biomarkers to exclude a SARD diagnosis [100][101][102][103][104][105][106][107][110][111][112][113][114][115].…”

Rapid onset of systemic lupus erythematosus with rarely observed cutaneous lesions

“…Presence of DFS70 antibodies that appeared at the same time as lupus-specific anti-dsDNA antibodies, requires a separate discussion. Although their presence rises controversies, it is commonly agreed that if they are present alone, the autoimmune background of a disease may be usually excluded [36]. But in case of their simultaneous presence with specific antibodies -as it was in the presented case -they do not negate the diagnosis of SLE.…”

“…Odrębnego omówienia wymaga obecność przeciwciał DFS70, które stwierdzono równolegle ze swoistymi dla tocznia przeciwciałami skierowanymi przeciwko dsDNA. Ich obecność wzbudza szereg kontrowersji, jednak powszechna jest teza, że jeśli występują jako jedyne, to zwykle można wykluczyć autoimmunologiczne tło choroby [36]. Ich jednoczesna obecność z przeciwciałami swoistymi, jak w przedstawionym przypadku, nie wyklucza diagnozy SLE.…”