Current views on lupus in children

Abstract

Purpose of reviewThis manuscript provides an update on clinical and pathophysiological features of juvenile-onset systemic lupus erythematosis (jSLE), challenges applying adult-derived classification criteria, and recent advances in treatment and care.Recent findingsSignificant scientific advances have improved the understanding of genetic factors (both genetic causes and risk alleles) and associated phenotypic features. Panels of urine/blood biomarker candidates aid in diagnosing jSLE, monitoring disease activity and predicting treatment response. Available classification criteria have been extensively assessed, with differences in clinical and immunological phenotypes of patients across age groups and ethnicities affecting their performance in jSLE. Therapeutic options remain limited and are based on protocols for adult-onset SLE patients. International efforts to inform development of a treat-to-target (T2T) approach for jSLE have yielded cohort-level evidence that target attainment reduces the risk of severe flare and new damage, and treatment compliance.SummaryRecent studies have significantly improved our understanding of jSLE pathogenesis, highlighting important differences between jSLE and adult SLE, and providing the basis of biomarker development and target-directed individualized treatment and care. Future work focused on development of a T2T approach in jSLE is eagerly awaited.

Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement

“…To shed light on the role of NK cells in lupus clinical features, we related apoptosis protein expressions with the manifestations with higher risk of morbidity and mortality. Although nephritis is one of the most serious manifestations of jSLE, it still does not have an ideal biomarker to detect early renal flare ( 1 , 4 ). In this study, patients with jSLE with nephritis had reduced TRAIL, Bcl-2, TNFR1, and Fas expressions in NK cells when compared to healthy controls and to those without nephritis, confirming the great imbalance of the apoptosis process in patients with jSLE with nephritis, which favors disease development and maintenance.…”

“…A stronger genetic predisposition is observed in patients with early-onset (≤ 6 years of age) jSLE ( 1 – 4 , 37 ). Nonetheless, the three patients with early-onset jSLE and the 6 patients with prepubertal disease onset (≤ 8 years of age) had apoptosis-related protein expressions similar to the whole group (data not shown) precluding additional analyses.…”

“…There is evidence that jSLE has stronger genetic background and interferon (IFN) signature (1)(2)(3). Although self-reactive T and B lymphocytes are critically linked to lupus development, others cells as neutrophils, monocytes, and natural killer (NK) cells have also been implicated (1,(4)(5)(6). Lupus pathogenesis is mainly ascribed to increased production and/or inefficient removal of dead cell debris (1,4,(7)(8)(9)(10)(11)(12).…”

“…Although self-reactive T and B lymphocytes are critically linked to lupus development, others cells as neutrophils, monocytes, and natural killer (NK) cells have also been implicated (1,(4)(5)(6). Lupus pathogenesis is mainly ascribed to increased production and/or inefficient removal of dead cell debris (1,4,(7)(8)(9)(10)(11)(12). In this regard, our group demonstrated that patients with jSLE have altered expressions of the apoptosis-related proteins Fas and Bcl-2 in lymphocytes and monocytes, as well as altered sFas, sTRAIL, sFasL, and sMer levels, which related to disease activity and/or nephritis (13)(14)(15)(16)(17).…”

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus (jSLE)

“…Approximately 15–20% of patients develop SLE before their 16th birthday and are therefore diagnosed with juvenile-onset systemic lupus erythematosus (jSLE) [ 12 , 13 ]. Notably, when compared to disease-onset in adulthood, jSLE is associated with higher and more wide-spread organ involvement at diagnosis, increased organ damage, and increased need for anti-inflammatory/immune-modulating treatments including corticosteroids [ 1 , 2 , 4 , 8 , 14 – 16 ]. Among children (and adults), minority ethnicities are most frequently and severely affected, and preliminary studies linked a high number of risk alleles in an individual with early disease-onset, increased clinical disease activity and severity, as well as Black African ethnicity [ 5 , 9 , 17 ].…”