Abstract-We showed earlier that activating autoantibodies against the angiotensin II type 1 (AT 1 ) receptor (AT1-AA) circulate in preeclamptic women. They may be involved in the pathogenesis of preeclampsia. Protein alignment suggests that the binding site for AT1-AAs is highly homologous to the capsid protein VP2 of parvovirus B19. We performed a prospective, nested, case-control study of 30 gestational age-matched women with preeclampsia and 30 normotensive pregnant women. We measured AT1-AA, soluble fms-like tyrosine kinase 1 (sFlt-1), and serum immunoglobulin G against parvovirus B19 proteins. AT1-AAs were present in 70% of preeclamptic patients and absent in 80% of controls. Prediction by AT1-AA was improved in late-onset preeclampsia. The discrimination for sFlt-1 was 96%. We did not find an interaction between sFlt-1 and AT1-AA. A human monoclonal immunoglobulin G antibody against parvovirus B19 VP2-protein showed a positive reaction in the AT1-AA bioassay, which could be blocked by an AT 1 receptor blocker, as well as by the epitope amino acid sequence. Immunoglobulin G against parvovirus B19 proteins was similarly distributed between preeclamptic patients and controls and had no significant importance. We detected significantly more AT1-AA in women with an immune response corresponding with parvovirus B19 infection corresponding with a distant viral infection associated with virus elimination. We concluded that AT1-AAs were common in patients with preeclampsia in a prospective case-control study, although sFlt-1 was a superior biomarker. AT1-AA may represent a better marker for late disease, whereas sFlt1 is a better marker for early onset disease. Key Words: preeclampsia Ⅲ activating autoantibodies Ⅲ angiogenesis Ⅲ parvovirus B19 Ⅲ molecular mimicry P reeclampsia is defined as new-onset hypertension after 20 weeks' gestation accompanied by new-onset proteinuria; the condition causes acute morbidity and mortality. 1,2 The incidence is 2% to 5% worldwide and is associated with subsequent cardiovascular diseases in both mother and child. 3 The pathogenesis is unknown but is likely to be multifactorial. 4 We described circulating autoantibodies directed at the second extracellular loop of the angiotensin (Ang) II type 1 (AT 1 ) receptor (AT1-AA) in women with preeclampsia. 5 AT1-AAs induce reactive oxygen species, inhibit trophoblast migration, and occur in rat models. 6 -8 AT1-AAs induced preeclampsia-like symptoms in C57BL/6J mice by passive transfer. 9 However, AT1-AAs are not specific for preeclampsia and also occur in patients with humoral kidney transplant rejection. 10 An epitope on the second extracellular loop of the human AT 1 receptor (AFHYESQ) represents the binding site for AT1-AAs; the same sequence inhibits the AT1-AAmediated effects completely in vivo and in vitro. The epitope is highly homologous to the capsid protein VP2 from parvovirus B19 (AFHYETQ).Parvovirus B19 is a single-stranded DNA virus and can cause erythema infectiosum, a generally (but not always) mild childhood exanthem. 11,...
As bstract. Serum ionized calcium levels are lower and immunoreactive parathyroid hormone levels are higher in the spontaneously hypertensive (SH) rat than in the normotensive Wistar-Kyoto (WKy) control.We postulated that there is either a defect in the regulation ofvitamin D metabolism by parathyroid hormone or that the gut target organ for vitamin D in the SH rat is unresponsive. To test these hypotheses we measured serum concentrations of vitamin D metabolites and intestinal transport of calcium and sodium. Compared with that of WKy controls, in vitro calcium transport by duodenal sacs of the SH rat was decreased (P < 0.001) at 5 wk, before the development of hypertension, and at 12 wk, after hypertension was well established. When measured in vivo in the most proximal 20 cm of small intestine, maximum velocity (Vmax) for calcium transport was decreased (P < 0.05) and net absorption of sodium and water was increased (P < 0.05) in SH rats as compared with WKy rats. Vmax for calcium transport was also decreased (P < 0.05) in the most distal 20 cm of small intestine of SH rats, but net sodium and water transport were the same in SH and WKy rats. At 12 wk, serum concentration of 1 ,25-dihydroxycholecalciferol [1,2D3] was the same in both SH and Wry groups, but its precursor, 25-hydroxycholecalciferol, was increased (P < 0.05) in the SH rat. We conclude that in the SH rat: (a) the concentration of 1,25-(OH)2D3 is inappro-
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