Infusion of anti-DFS70 antibodies prolonged survival of lupus-prone mice

Abstract

Background Systemic-lupus-nephritis is a chronic autoimmune disease characterized by immune complex deposition and a flare of autoantibodies and leading to renal injury. Objectives To expose anti-Dense-Fine-Speckled-70 (DFS70)-antibodies to genetically-prone-lupus-mice. Methods NZBXW/F1 female mice were monitored for the onset of glomerulonephritis by proteinuria upon infusion of anti-DFS70 (40 μg/mouse), commercial-human-IgG (cIgG) or phosphate-buffered-saline (PBS) as controls. The survival time was detected by mice death. Circulating anti-dsDNA were tested by ELISA. Proteinuria, was defined by a standard semi-quantitative-Bayer-Multistix-dipstick. Kidney histology was analyzed by periodic-acid–Schiff-PAS staining. Results A significantly higher percentage of anti-DFS70-infused mice exhibited prolonged survival time as compared with cIgG and PBS-subjected mice (p < 0.022). One mouse out of 10 mice injected with anti-DFS70-antibodies died at week 36, whereas, 6 out of 10 mice subjected with PBS found dead at this time. Eighty percent of anti-DFS70 injected mice did not show severe glomerulonephritis by histology. Conclusions anti-DFS70 attenuated the progression of glomerulonephritis and prolonged the survival time. Circulating anti-DFS70-autoantibodies may confer a protective role against renal injury in murine-lupus-nephritis. Our data may propose a novel therapy approach for lupus patients.

Anti-DFS70 Antibodies Are Associated With Proliferative Lupus Nephritis and Renal Pathological Activity

“…Although the treatment strategies (Supplemental Table 1) and disease duration of our LN and NLN-SLE patients were different, which was almost inevitable in clinical settings, a similar prevalence of anti-DFS70 antibodies in our newly onset LN and NLN-SLE patients was also be observed. Murine studies have demonstrated the protective effects of anti-DFS70 antibodies purified from HI in attenuating LN development in lupus-prone mice (11). However, our clinical observations do not support the protective role of anti-DFS70 antibodies in SLE patients.…”

“…To date, no defined autoantibodies or clinical manifestations have been found to be associated with anti-DFS70 antibodies (7). In a recent paper, Aljadeff et al (11) reported that anti-DFS70 antibodies purified from HI tempered renal progression in lupus-prone mice. They inferred that anti-DFS70 antibodies potentially could protect against renal injury in SLE patients (11).…”

“…In a recent paper, Aljadeff et al (11) reported that anti-DFS70 antibodies purified from HI tempered renal progression in lupus-prone mice. They inferred that anti-DFS70 antibodies potentially could protect against renal injury in SLE patients (11). However, clinical studies (5,6,10) did not find an association of anti-DFS70 antibodies with LN in SLE patients.…”

Do anti-DFS70 antibodies temper disease activity and progression in SLE?

“…In addition, a hypothesis suggesting that anti-DFS70 are protective was previously considered. 5 In summary, the findings of Aldajeff et al in a murine model of SLE exposed to anti-DFS70 1 need further clarification but are nevertheless interesting and might be supported by earlier studies of human SLE. However, longitudinal studies are needed to clarify the longer-term importance or protective effects of anti-DFS70 in SLE.…”

“…Sir, We read with great interest the recently published study by Aljadeff et al 1 reporting that weekly infusions of affinity-purified human anti-DFS70 antibodies into NZBxW/F1 mice resulted in improved survival rates, which might be attributed to the observation that 80% of the anti-DFS70 injected mice did not exhibit histological evidence of glomerulonephritis (GN). It is not clear if the remaining 20% had severe GN.…”