Neuropathological spectrum in systemic lupus erythematosus: A single institute autopsy experience

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by circulating autoantibodies and immune complexes involving virtually every organ of the body. However, with respect to central nervous system (CNS), the mechanism of injury is still debated as complement mediated or thrombo-ischemic in nature. We studied the spectrum of neuropathological changes in twelve autopsy cases of SLE and evaluated the role of immune-complexes and complement activation in contributing to the thrombo-ischemic injury and correlated these features with clinical profile.

Autopsy records of all cases of SLE over a period of 20 years (2000-2019) were reviewed. Clinical history including neuropsychiatric symptoms and detailed histopathological analysis was performed. Direct immunofluorescence for IgM, IgG, IgA, C1q, C3, C4d, Kappa, Lambda and immunohistochemistry for C5b-9 was performed on lesional areas in paraffin embedded brain sections. Control tissue from brain was taken from two patients who died of sudden cardiac event.

Our cohort comprised of 12 cases with age range from 12 to 40 years and all were female patients. Microinfarction and vasculopathy seen in eight cases were the commonest findings. Four cases with microinfarcts had non-bacterial thrombotic endocarditis in heart. Microthrombi adjacent to microinfarcts were seen in 4 cases. Variable deposition of immunoglobulins (predominantly IgG) and complements (C1q, C3, C4d) was evident in cortical arterioles (2 cases) and small capillaries (1 case). Neurological symptoms were seen in four cases, of which, three had associated invasive fungal infection with secondary vasculitis. Active lupus vasculitis was identified in a single case. C5b-9 immunoexpression was not detected in any of the cases.

Our study adds observational data to the existing literature that the predominant neuropathological features of SLE are related to thrombo-ischemic injury and small vasculopathic changes. Only in a minor subset (25%), it is mediated by immune-complexes and complements. Immune-complex deposition on immunofluorescence in cortical vessels (cerebral lupus vasculopathy) is a novel finding which has not been reported earlier.