Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease, has extremely varied clinical manifestations and complex pathogenesis. 

A recent review by Zucchi et al summarizes the most relevant data about SLE that emerged during 2021 concerning its pathogenetic pathways, biomarkers, clinical manifestations, new drugs and new therapeutic strategies.

Regarding pathogenesis, new evidence favors the association between sex bias in SLE and epigenetically-induced modifications in X-linked immunity genes expression, especially in B cells-driven autoimmunity. The evidence also confirms the role of interleukin (IL)-18 in SLE disease progression and activity. Also, the T helper 17 pathway may be involved in several aspects of SLE disease pathogenesis.

The review also described the role of tRF-His-GTG-1, IgG2 isotype antibody panel and anti-human endogenous retrovirus K envelope autoantibodies as the potential diagnostic biomarkers for SLE. Additionally, it described neurotrophic factors, IL-33, soluble ST2 and soluble CD14 as the potential biomarkers for disease monitoring. The study found seric syndecan-1, hyaluronan and thrombomodulin; urinary epidermal growth factor; a combination of urinary lipocalin-like prostaglandin D synthase, transferrin, ceruloplasmin, monocyte chemoattractant protein-1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as the potential biomarkers for active lupus nephritis. Further, biomarkers like apolipoprotein C3 and amylin are beneficial for determining insulin resistance and anti-protein C antibodies to detect increased thromboembolic risk.

Regarding clinical manifestations and comorbidities, the review briefed that neuropsychiatric (NP) events due to SLE have a higher resolution rate contrasting those not attributed to SLE. The resolution is more common in Asians and central/focal NP manifestations. In lupus nephritis, the occurrence of acute renal dysfunction, arterial hypertension and corticosteroid dose independently predict damage increase over time. It highlighted the association of SLE with a 1.8-fold increased mortality rate for all-cause mortality. Further, it underlined the increase in hospitalized infection rates over time in patients with SLE, with sepsis being the commonest. 

For new potential therapeutic targets, the review declared combination therapy with rituximab and belimumab as promising treatments for refractory patients with good safety profiles. It explained that in the extension of phase II studies, both anifrolumab and atacicept have also demonstrated acceptable safety for extended treatment periods.

The review also discussed the new therapies and therapeutic strategies. It mentioned that glucocorticoid tapering and withdrawal could be safe in patients with clinically quiescent SLE. Belimumab may be an effective add-on therapy for adult patients with active lupus nephritis, and calcineurin inhibitors (voclosporin and tacrolimus) may show promising results in renal involvement. In patients with lupus nephritis, maintenance therapy with cyclosporine, mycophenolate mofetil or azathioprine possess similar efficacy in achieving and maintaining complete renal remission at 1 and 8 years. 

Regarding treat-to-target remission, lupus low disease activity state (LLDAS) and patient-reported outcomes, the study regarded no treatment as an ideal target for SLE, quoting the 2021 DORIS definition of remission in SLE. It mentioned that the patients and physicians might have different expectations of remission and low disease activity states, with the improvement of fatigue, joint pain and quality of life as the ideal treatment goals from the patient’s perspective.

Furthermore, in SLE patients suffering from coronavirus disease 2019 (COVID-19), only lupus nephritis could cause severe to critical COVID-19; and none of the medications used to treat SLE are significantly associated with the severity of the COVID-19 infection. Most patients with SLE and confirmed COVID-19 could produce and maintain a serological response despite the use of immunosuppressants. Furthermore, these patients can tolerate the COVID-19 vaccination well. 

This study very meaningfully and briefly explains many exciting data about SLE and news regarding pathogenesis, clinical manifestations, therapeutic strategies and patients reported outcomes. These data also underline the growing interest of researchers in this complex disease. 

Source: Zucchi D, Elefante E, Schilirò D, et al. One year in review 2022: systemic lupus erythematosus. Clin Exp Rheumatol. 2022;40(1):4-14.