Molecular medicine (Cambridge, Mass.) · 2026
Serum vs. tissue cytokine dysregulation in SLE-associated myocarditis: a hypothesis from an African cohort perspective.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ollewagen Tracey, du Toit Riette, Karamchand Sumanth, Doubell Anton F, Herbst Philip G, Smith Carine
Аннотация
BACKGROUND: Clinical lupus myocarditis (LM) occurs in 5-10% of systemic lupus erythematosus (SLE) patients while sub-clinical presenting in approximately 40%. To date, an in-depth cytokine profile of cardiac tissue is lacking, yet vital to understanding disease mechanisms. This study aimed to correlate cardiac tissue inflammatory profile to standard of care (SOC) parameters (serum biomarkers and cardiac MRI (CMR)) in an African mixed-ancestry LM population.
METHODS: One control (n = 6) and two SLE cohorts, SLE (n = 13) and SLE with myocarditis (SLE-M; n = 14) were recruited. Serum cytokines were assessed using immunoassays. SLE patients underwent SOC clinical assessments (serology, CMR) and endomyocardial biopsy (EMB, LM only). EMB tissue was immunostained for inflammation, fibrosis and tissue damage.
RESULTS: Systemic inflammation in LM was confirmed with increased serum (s) sTNF-α (p < 0.05), sIL-18 (p < 0.05), sIL-6 (p < 0.01), sIL-10 (p < 0.01) and sVCAM-1 (p < 0.001). Higher sIL-10 (associated with disease activity) and sVCAM-1 (endothelial activation) were observed in SLE-M vs. SLE (p < 0.01). Matching serum and tissue parameters showed no correlation, suggesting a disconnect between circulation and tissue compartments. Functionally contradictory negative correlations between sTNF-α, sVCAM-1 and tissue (t) tIL-6 (both p < 0.05) implied a relative lower presence of tIL-6, which would limit conversion from a pro-inflammatory to an anti-inflammatory, reparative state (supported by accompanying low tIL-10). This limited tIL-6 presence was further implicated by negative correlations with CMR inflammation and necrosis/fibrosis (T1, T2). Anti-Ro/La correlated to TGF-β (p < 0.05), key in fibrosis development. Fibrosis markers did not correlate with CMR fibrosis suggesting a temporal lag before detectable CMR fibrosis.
CONCLUSIONS: Based on presented exploratory data, we hypothesize that inadequate activation of myocardial IL-6 and IL-10 may impair inflammatory regulation. Data suggest that myocardial pro-fibrotic signaling may be detectable at a time point preceding CMR-detectable fibrosis. Purpose-designed research to test this hypothesis of limited IL-6 presence is required to inform on future therapeutic strategies.
METHODS: One control (n = 6) and two SLE cohorts, SLE (n = 13) and SLE with myocarditis (SLE-M; n = 14) were recruited. Serum cytokines were assessed using immunoassays. SLE patients underwent SOC clinical assessments (serology, CMR) and endomyocardial biopsy (EMB, LM only). EMB tissue was immunostained for inflammation, fibrosis and tissue damage.
RESULTS: Systemic inflammation in LM was confirmed with increased serum (s) sTNF-α (p < 0.05), sIL-18 (p < 0.05), sIL-6 (p < 0.01), sIL-10 (p < 0.01) and sVCAM-1 (p < 0.001). Higher sIL-10 (associated with disease activity) and sVCAM-1 (endothelial activation) were observed in SLE-M vs. SLE (p < 0.01). Matching serum and tissue parameters showed no correlation, suggesting a disconnect between circulation and tissue compartments. Functionally contradictory negative correlations between sTNF-α, sVCAM-1 and tissue (t) tIL-6 (both p < 0.05) implied a relative lower presence of tIL-6, which would limit conversion from a pro-inflammatory to an anti-inflammatory, reparative state (supported by accompanying low tIL-10). This limited tIL-6 presence was further implicated by negative correlations with CMR inflammation and necrosis/fibrosis (T1, T2). Anti-Ro/La correlated to TGF-β (p < 0.05), key in fibrosis development. Fibrosis markers did not correlate with CMR fibrosis suggesting a temporal lag before detectable CMR fibrosis.
CONCLUSIONS: Based on presented exploratory data, we hypothesize that inadequate activation of myocardial IL-6 and IL-10 may impair inflammatory regulation. Data suggest that myocardial pro-fibrotic signaling may be detectable at a time point preceding CMR-detectable fibrosis. Purpose-designed research to test this hypothesis of limited IL-6 presence is required to inform on future therapeutic strategies.