Prevalence of antiphospholipid and antinuclear antibodies in children with epilepsy.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous thrombosis or arterial occlusive events and fetal losses associated with elevated levels of antiphospholipid antibodies (aPLs). MATERIAL/METHODS: The presence of antinuclear, anti-beta2-glycoprotein I, and anticardiolipin antibodies were investigated in 60 consecutive children with epilepsy who were followed up in a single Hungarian center. RESULTS: Almost 50% (28/60) of the patients were ANA positive. Twelve (20%) patients had moderate titer (1:160) of ANA. Anti-C1q antibody was positive in 4 cases, all of them symptom free considering renal manifestation of lupus. Interestingly, only 1 child had aCL antibody, while 6/43 patients were LAC positive. Five were also ANA positive among the LAC positive patients (4 children with moderate titer). Anti-beta2GPI antibody positivity was not detected in this cohort of patients. CONCLUSIONS: The clinical relevance of aPL tests in childhood are difficult to explain. In the present study, obviously lower total prevalence of aPLs (aCL and anti-beta2GPI) was observed in children with epilepsy than in previously reported investigations (20-30%). The higher amount of LAC-positive patients indicates that coagulation studies (LAC) should be included in the neuroimmunological assessment of suspected APS patients with epileptic disorders. The difference between the results of serological and LAC studies could be explained by the possible positivity of other, uninvestigated antibodies. The wide spectrum of detected immunological alterations highlight the importance of the participation of pediatric rheumatologists in the management of patients with idiopathic epilepsy or with secondary induced autoimmune disease due to antiepileptic medications.

Antinucleosome antibodies and decreased deoxyribonuclease activity in sera of patients with systemic lupus erythematosus.

Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75%+/-12.1%) than in the controls (81.3%+/-9.25%) (P<0.001). DNase activity in patients with UCTD (64.9%+/-18.2%; P=0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3+/-851) than the controls (1.44+/-2.77; P<0.01) or UCTD patients (39.9+/-57.7; P<0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.

Functional mapping of the Fc gamma RII binding site on human IgG1 by synthetic peptides.

Receptors specific for the Fc part of IgG (Fc gamma R) are expressed by several cell types and play diverse roles in immune responses. Impaired function of the activating and inhibitory Fc gamma R may result in autoimmunity. Thus, the modulation of IgG-Fc gamma R interaction can be a target for the development of treatments for some autoimmune and inflammatory diseases. This study addresses the localization and functional characterization of linear sequences in human IgG1 which bind to Fc gamma RII. Peptides with overlapping sequences derived from the CH2 domain of human IgG1 between P(234) and S(298) were synthesized and used in binding and functional experiments. Binding of the peptides to Fc gamma R was assayed in vitro and ex vivo, and peptides found to interact were functionally tested. The shortest effective peptide was T(256)-P(271), which bound to soluble recombinant Fc gamma RIIb with K(d)=6 x 10(6) M(-1). The biotinylated peptides R(255)-P(271) and T(256)-P(271) complexed by avidin exhibited functional activity; they induced Fc gamma RIIb-mediated inhibition of the BCR-triggered Ca(2+) response of human Burkitt lymphoma cells, and inflammatory cytokine production (TNF-alpha and IL-6) by the human monocyte cell line MonoMac. In conclusion, our results suggest that the selected peptides functionally represent the Fc gamma RII-binding part of IgG1.