Endothelium and the brain in CNS lupus.
Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is common and results in different clinical manifestations. Several pathogenic mechanisms have been suggested to play a role in determining such a variety of clinical symptoms. The thrombophilic state associated to the presence of antiphospholipid antibodies has been suggested to be responsible for a noninflammatory vasculopathy which causes clear ischaemic events as well as alterations of the cerebral microcirculation that are likely associated to seizures, cognitive dysfunction or psychosis. Although less frequent, a true vasculitic process affecting cerebral circulation has also been reported. In both cases, brain endothelium does represent the target of the pathogenic mechanisms. Brain endothelial cells display peculiar functional and phenotypical characteristics in comparison with endothelial cells from other anatomical districts, raising the possibility that this might be the reason for its susceptibility in lupus disease. We review and present data suggesting that a higher and firmer expression of beta 2 glycoprotein I on endothelial cell membranes can be responsible for a selective damage/activation by circulating anti-beta 2 glycoprotein I, and that antiendothelial cell antibodies crossreact with brain endothelium and in some cases, specifically bind brain endothelial cells only in lupus patients with central nervous involvement.
Meroni
P L
PL
Allergy and Clinical Immunology Unit, Department of Internal Medicine, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy. pierluigi.meroni@unimit.it
Tincani
A
A
Sepp
N
N
Raschi
E
E
Testoni
C
C
Corsini
E
E
Cavazzana
I
I
Pellegrini
S
S
Salmaggi
A
A
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000032:analysis / Q000276:immunology*; D001666:Binding Sites, Antibody; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology*; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I