Serological Marker Linked With Higher Ferritin, Macrophage Activation, in SLE

Anti-ribosomal P protein antibodies (anti-ribo P) are a risk factor for higher ferritin levels and may be directly associated with macrophage activation in patients with systemic lupus erythematosus (SLE), according to new research.

The findings could make it easier to diagnose SLE complications, and might also give clinicians better insights into which medications are most likely to be successful in individual patients, according to corresponding author Yoshiyuki Arinuma, MD, of Japan’s Kitasato University School of Medicine, and colleagues. Their report was published in the International Journal of Rheumatic Diseases.

SLE is typically identified by SLE-specific autoantibodies, Arinuma and colleagues explained, though innate immune hypersensitivity is also present in SLE. Innate immune hypersensitivity involves the hyperactivation of cells such as macrophages, neutrophils, dendritic cells, and others. Accordingly, macrophage activation syndrome (MAS) has been identified as a complication of SLE in some patients. Serum ferritin levels are a characteristic of MAS, indicative of disease activity.

Anti-ribo P antibodies have been associated with lupus severity, though it is not clear exactly what role, if any, it plays in SLE. However, anti-ribo P does appear to impact immune and neuronal cells, the authors said, and may affect systemic inflammation, which in turn can impact lupus activity.

Arinuma and colleagues wanted to better clarify what role, if any, anti-ribo P plays in patients with SLE. They also wanted to understand the relationship between anti-ribo P, clinical characteristics, and biomarkers like serum ferritin.

The investigators recruited 127 patients with active SLE, all of whom were patients at their hospital between 2007 and 2019. Patients were assessed for lupus disease activity and serum samples were taken prior to initial or reinforcement immunosuppressive therapy. They also looked at a control group of 140 patients with non-SLE autoimmune diseases in order to gain a better understanding of the association between anti-ribo P and SLE.

Arinuma and colleagues conducted a logistic regression analysis to see which SLE risk factors were affected by anti-ribo P and to identify correlations between anti-ribo P and clinical factors.

They found anti-ribo P was much higher among the patients with SLE compared to the control group. Patients with anti-ribo P had a more than eightfold increase in risk for elevated serum ferritin (odds ratio, 8.432), and patients who were positive for anti-ribo P had higher serum ferritin levels compared to patients who were negative for anti-ribo P.

Notably, while investigators found that anti-ribo P and serum ferritin levels were positively correlated in patients with SLE, the same was not true for serum interleukin 6 (IL-6).

“These results suggest that anti-ribo P is able to develop hyperferritinemia but not in a systemic inflammation fashion surrogated by IL-6,” the authors wrote. “The gap between anti-ribo P and IL-6 can be considered as a result of complex cytokine production in SLE.”

The investigators noted that their finding was in line with previous research that found patients with SLE and MAS did not have elevated levels of serum IL-6.

Arinuma and colleagues concluded that since anti-ribo P appears to activate innate immunity through macrophages independent of IL-6, the presence of anti-ribo P in patients with SLE could make it easier to diagnose MAS and more effectively treat SLE.

Reference

Arinuma Y, Hirohata S, Isayama T, et al. Anti-ribosomal P protein antibodies in patients with systemic lupus erythematosus is associated with hyperferritinemia. Int J Rheum Dis. Published online November 18, 2021. doi:10.1111/1756-185X.14245