Arthritis Rheum

Arthritis Rheum. lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal antibody titers to SSA/Ro, SSB/La, or Ro52 were detected over the course of therapy or at delivery. There were no safety issues. Conclusions IVIG at doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers. Having established safety with this protocol and SF1126 feasibility of patient enrollment, subsequent preventative studies may be considered, perhaps to include higher doses of IVIG. cardiac pacing [10]. None have significantly altered mortality. Accordingly, strategies aimed at preventing disease before immutable scarring ensues, assume high priority. Although it is disappointing that animal models have not fulfilled Kochs postulates assuring an effect of the antibody per se, this is likely due to the fact that antibodies are necessary but insufficient. Our approach to prevention considered the necessity of maternal antibody as well as consequent fetal factors in the cascade to pathogenesis. Intravenous gamma globulin (IVIG) has been of benefit in a variety of immune-mediated and inflammatory diseases. Rationale for its use in CHB is based on our working SF1126 hypothesis of the pathogenesis of disease. Tissue injury in the SF1126 fetus is presumed to depend on FcRn-mediated transplacental passage of maternal IgG autoantibodies [11]. Anti-SSA/Ro-SSB/La antibodies, by binding to translocated antigen on the surface of apoptotic cardiocytes generated during remodeling of the conduction system and surrounding tissue, may inhibit the normal physiologic removal of these cells [12, 13]. Uncleared opsonized apoptotic cardiocytes may be subsequently efferocytosed by infiltrating macrophages with release of pro-inflammatory and profibrosing cytokines which transdifferentiate cardiac fibroblasts to a scarring phenotype [13, 14]. This scenario supports the consideration of prophylactic IVIG based on two presumed mechanisms of efficacy. The first exploits the saturation of FcRn by IVIG. This should decrease fetal exposure to anti-SSA/Ro-SSB/La by accelerating IgG catabolism in the maternal circulation EBI1 and decreasing placental transport [15, 16]. The second exploits the attenuation of anti-inflammatory responses by increasing the macrophage expression of FcRIIB [17]. This would represent a downstream effect in the targeted organ. Precedent for the use of IVIG is the encouraging report of only 1 1 recurrent case of CHB in 8 mothers with previously affected children [18] and murine data demonstrating a decrease in placental transport of human anti-SSA/Ro-SSB/La antibodies following IVIG [19]. Accordingly, a prospective US based multi-center open-label trial to determine the efficacy and safety of IVIG on the prevention of CHB in women with anti-SSA/Ro antibodies and a previous child with neonatal lupus was initiated. Treatment comprised IVIG at 400 mg/kg, dosed every 3 weeks from 12 to 24 weeks of gestation. The primary outcome was the development of 2nd or 3rd degree CHB. METHODS Subjects Subjects entered this prospective multi-center open label clinical trial between January 2007 and January 2009. A total of 17 women from centers across the US signed consent forms approved by the Institutional Review Board at the site of their infusion. Four mothers provided consent as participants of the Research Registry for Neonatal Lupus to release medical records and send blood specimens but received drug as prescribed by their treating physicians who elected to follow and adhere to the study protocol. Of the 21 women enrolled, there was one screen failure due to a spontaneous miscarriage at 9 weeks prior to initiation of the study protocol. Enrollment required all of the following inclusion criteria documentation of anti-SSA/Ro and/or anti-SSB/La antibodies a previous child with one of the following: CHB (any degree) documented by EKG if live birth and/or echocardiogram and/or histology if fetal demise; characteristic NL rash confirmed by photograph revealing annular lesions, dermatology note, and/or biopsy; CHB and rash; current intrauterine pregnancy 12 wk with normal heart beat and structure. A patient was excluded for any of the following: current dose of prednisone 20mg or any dose of dexamethasone level of Ig A below normal values for laboratory presence of any structural abnormalities of the fetal heart that could cause CHB, ie, L-transposition of the great arteries, AV septal defect, or heterotaxias. Mothers could be clinically asymptomatic or have symptoms of a rheumatic disease. Rheumatologic disease was classified on the basis of case report forms filled out by the participating rheumatologists, obstetricians and cardiologists performing the echocardiograms and verified by telephone interviews and review of medical records when available (by J.P.B., C.L. and P.M.I). The following categories were assigned asymptomatic.