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Background: Anti-β₂-glycoprotein-I (anti-β₂GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β₂GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions., Objective: To evaluate the fine specificity of anti-β₂GPI in adults and infants., Methods: Three groups were examined-group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS., Subjects: were selected based on positive anti-β₂GPI IgG results. Serum samples were tested for anti-β₂GPI IgG D1 and D4/5 using research ELISAs containing recombinant β₂GPI domain antigens., Results: Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B., Conclusions: The specificity for D4/5 suggests that anti-β₂GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the 'innocent' profile of such antibodies.

Objective: Anti-β2 GPI are a formal laboratory criterion for the antiphospholipid syndrome (APS). They were demonstrated to be a risk factor for thrombosis and fetal losses but can also be detected in patients with systemic autoimmune disease (SAD), in healthy adults individuals and pre-school children. It has been suggested that different subpopulations of anti-β2GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identified in patients with non-thrombotic conditions., Methods: We studied 48 patients with SAD (32 systemic lupus erythematosus, 16 undifferentiated connettive tissue disease), 64 patients with APS, 57 one-year-old healthy children born to mother with SAD, 33 children with atopic dermatitis. All subjects were IgG anti-β2 GPI positive. The specificity of anti-β2 GPI was investigated using ELISA research products containing recombinant β2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-β2 GPI were tested at a validated home-made ELISA routinely performed in our laboratory. No thrombotic events were recordered in patients with SAD and in both groups of children., Results: Patients with SAD and APS showed prevalent reactivity for D1 while children in both groups preferentially recognize D4/5., Conclusions: IgG anti-β2 GPI against D1 seem to cluster in patients with systemic autoimmune conditions. Their pathogenic potential in determine APS manifestations may be mitigated by adequate prophylaxis.

Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide is used to kill phagocytosed micro-organisms in neutrophils, eosinophils, monocytes and macrophages. The leukocyte NADPH oxidase is composed of five subunits, of which the enzymatic component is gp91-phox, also called Nox2. This protein is encoded by the CYBB gene on the X chromosome. Mutations in this gene are found in about 70% of all CGD patients. This article lists all mutations identified in CYBB in the X-linked form of CGD. Moreover, apparently benign polymorphisms in CYBB are also given, which should facilitate the recognition of future disease-causing mutations., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Anti-β₂glycoprotein I antibodies (a-β₂GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-β₂GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a-β₂GPI in different clinical situations., Methods: We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-β₂GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-β₂GPI positive. IgG a-β₂GPI were performed by homemade ELISA, while IgG a-β₂GPI D1 and D4/5 were tested on research ELISAs containing recombinant β₂GPI domains antigens., Results: One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-β₂GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-β₂GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children., Conclusions: A-β₂GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the "innocent" profile of a-β₂GPI in children.

The registry is an European, multicentre, prospective and longitudinal study which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). In this article we report preliminary results obtained from 138 mothers and 141 babies (three twin pregnancies). At birth, 16.3% of neonates were less than 37 weeks of gestation and 17% were low birth weight; in addition, 11.3% of neonates were small for gestational age. No cases of neonatal thrombosis were observed. During follow-up period five children showed behavioral abnormalities. A long term clinical follow-up will be necessary to evaluate the neuropsychological development of these children.

Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

Influenza infection can cause mild to severe illness and can even lead to death. The best way to prevent infection is vaccination against influenza. Complications of influenza infection are not only a consequence of acute infection but can also present as late autoimmune response. Influenza is not frequently implicated as a trigger for autoimmune diseases, but case reports of autoimmune adverse events have been published even following influenza vaccination. In this article we review published data on autoimmune diseases following influenza infection and vaccination. We also discuss immunity of influenza infection in connection to pathogenesis of autoimmune response and autoimmune disease.

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrollment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations.

A 17-year-old boy with refractory psoriatic arthritis and alpha-1 antitrypsin deficiency who developed a syringotropic hypersensitivity reaction after 9 months of therapy with infliximab and leflunomide is described. Clinically, our patient showed a vasculitic-like skin rash involving both palms and soles, and histopathological examination revealed a syringotropic lymphocytic infiltrate directed toward the intra-epidermal portion of the eccrine ducts. These features have not been previously associated with infliximab or leflunomide therapy and represent a unique cutaneous hypersensitivity reaction that does not fit any known description of an immune-mediated hypersensitivity reaction.

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.

The paper presents an overview of clinical manifestations and histopathologic findings in different organs in microvascular thrombotic and microangiopathic antiphospholipid syndrome (MAPS). Subsets of antiphospholipid syndrome (APS) are presented and defined. Clinico-pathologic correlations seem insufficient so far, because of a lack of detailed systematic studies of the histopathology in different organs. Based on their own autopsy and biopsy studies, the authors propose a novel categorization of histopathologic lesions that occur in patients with classic and catastrophic APS. In addition to the already accepted category of a microvascular thrombotic type of lesions, microangiopathic lesions consistent with thrombotic microangiopathy are proposed to be included in new revised classification criteria for definite APS. Microvascular thrombotic and so far underestimated microangiopathic histopathologic lesions have been shown to appear in various combinations and of different ages in patients with both classic and catastrophic APS, which fits into the concept of MAPS. These preliminary findings of our studies are also in line with the most recent hypothesis of two main mechanisms in the pathogenesis of APS, emphasizing a key role of endothelial cell affection induced by aPL on the one hand and interference with coagulation cascade on the other side.

Objective: To evaluate the possibility of autoimmune responses following annual influenza vaccination in a large cohort of apparently healthy adults., Methods: Autoantibodies including antinuclear antibodies (ANA), anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I antibodies (anti-beta(2)-GPI), lupus anticoagulant (LA) and anti-extractable nuclear antigen antibodies (anti-ENA) were determined in 92 healthy adult subjects, staff at the University Children's Hospital Ljubljana. Blood samples were taken from each participant before the vaccination, 1 month and 6 months after the annual influenza vaccination., Results: Before the influenza vaccination, 26% of participants were positive for ANA, 16% for aCL, 7% for anti-beta(2)-GPI, 2% for LA and 1% for anti-ENA. There were no statistically significant differences in the percentage of positive ANA, aCL, anti-beta(2)-GPI, LA and anti-ENA before, 1 month and 6 months after the vaccination. One month after the vaccination 24% of participants demonstrated changes in the levels of autoantibodies including 15% of participants with increased level of autoantibodies or appearance of new autoantibodies. Six months after the vaccination 26% of participants demonstrated changes in the levels of autoantibodies including 13% of participants with increased level of autoantibodies or appearance of new autoantibodies. Persistently elevated levels of autoantibodies were observed in 7 (8%) participants and 2 showed progressively increased levels of IgM aCL or IgA anti-beta(2)-GPI, respectively. Eleven participants had a transient increase in autoantibodies., Discussion: Influenza vaccination in general did not alter the percentage of healthy adults with positive autoantibodies. Transiently or persistently increased levels of autoantibodies or appearance of new autoantibodies was demonstrated in up to 15% of apparently healthy adults after the influenza vaccination.

A 4-year-old boy with an atypical course of haemolytic uremic syndrome (HUS), who developed microangiopathic antiphospholipid-associated syndrome (MAPS) with signs of multiple organ failure during the course of his disease, is reported. Early and aggressive treatment with intravenous gammaglobulin, pulse methylprednisolone and plasmapheresis resulted in an excellent clinical recovery. Our patient showed a concomitant presence of multiple factors that could precipitate atypical HUS, including positive antiphospholipid antibodies, decreased level of factor H and positive anti-ADAMTS-13 antibodies. We suggest that, along with infections, autoimmune conditions or defined genetic abnormalities of complement regulatory genes, MAPS should be considered among the pathogenic mechanisms in patients with atypical HUS.

In genetically predisposed individuals, viruses, bacteria, or parasitic infectious agents are suspected of inducing autoimmunity and/or exacerbating autoimmune rheumatic diseases (ARD) once self-tolerance is broken. Although direct evidence for this association is still lacking, numerous data from animal models as well as from humans support the hypothesis of a direct contribution of pathogens to the induction of several ARD. This review focuses on the possible role of infectious agents as triggers of autoimmunity in systemic lupus erythematosus, polymyositis-dermatomyositis, antiphospholipid antibody syndrome, and primary vasculitis. Indeed, vasculitis may be a clinical manifestation of an infectious disease (secondary vasculitis). In addition, immune response abnormalities and immunosuppressive medications may be responsible for the high percentage of infectious complications in ARD patients. Recent therapeutic approaches aimed at lowering doses of cytotoxic agents and shortening duration of treatment with the most toxic drugs, have proved to be as effective as conventional regimens. New drugs and strategies aimed at preventing infections could further improve the outcome of ARD patients.

An association between infections and antiphospholipid antibodies (aPL) has been reported in several epidemiologic and experimental studies. Infection-induced aPL have been traditionally regarded as transient and were generally not associated with clinical features of antiphospholipid syndrome. The distinction between autoimmune and postinfectious aPL on the basis of requirement of binding cofactor is not absolute, and in recent years, several reports demonstrated that some patients can produce pathogenic antibodies in response to infection. Infections most frequently associated with antiphospholipid syndrome include parvovirus B19, cytomegalovirus, varicella-zoster virus, HIV, streptococcal and staphylococcal infections, gram-negative bacteria, and Mycoplasma pneumoniae.

A 10-year-old girl developed recurrent bouts of massive hemoptysis over a 9-month period. No obvious bleeding source was detected. Her pulmonary angiogram showed a pulmonary aneurysm of the second branch of the left main pulmonary artery as well as widespread irregularities of the pulmonary arteries including areas of stenosis and pruning. Elective embolization of the aneurysm did not control hemoptysis and emergency left upper lobectomy had to be performed. Histology showed large artery wall injury with acute leucocytoclastic inflammation, fibrinoid necrosis, granulomatous inflammation, and ectasia of vessel wall. This combination of abnormalities has not been described to date and represents the first case of isolated pulmonary arteritis in children prior to puberty., ((c) 2006 Wiley-Liss, Inc.)

The antiphospholipid syndrome (APS) is recognized increasingly as the most common acquired hypercoagulation state of autoimmune etiology and may occur as an isolated clinical entity (primary APS) or in association with an underlying systemic disease, particularly systemic lupus erythematosus (SLE). The major differences between pediatric and adult APS include absence of common acquired risk factors for thrombosis, absence of pregnancy-related morbidity, increased incidence of infection-induced antibodies, differences in cut-off values for determination of aPL and specific factors regarding long-term therapy in children. APS in children has been largely reported in patients with arterial or venous thromboses and less frequently in association with neurological or hematological manifestations. The presence of aPL in pediatric SLE can modify the disease expression and may be an important predictor of the development of irreversible organ damage. Two recently established international registries of neonates and children with APS provide a good opportunity to conduct large, prospective studies on the clinical significance of aPL and long-term outcome of pediatric APS.

We describe 3 patients who presented with features of macrophage activation syndrome (MAS) at the time of presentation of systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis, and Kawasaki disease. Immunohistochemical studies in the patient with SLE demonstrated extensive expression of CD163 on hemophagocytic macrophages, suggesting a possible role as a marker of MAS.

Nasal septal perforation has been well recognized in patients with various rheumatic diseases. To our knowledge, this condition has not been reported in children with systemic juvenile idiopathic arthritis (SJIA) or patients with adult onset Still's disease (AOSD). We describe 3 patients with persistent SJIA/AOSD who developed nasal septal perforation during the course of their disease. As illustrated by these cases, nasal septal perforation may develop as a rare complication of SJIA/AOSD and can be considered as part of the clinical spectrum of the disease. In one case the nasal septal perforation was associated with vasculitis.

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against beta(2)GPI (anti-beta(2)GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20.8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti-beta(2)GPI or LA activity (P < 0.001). Among subjects in whom changes of IgG anti-beta(2)GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P < 0.01). Analyses of paired data showed that differences in aCL or anti-beta(2)GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti-beta(2)GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti-beta2GPI and the levels were increasing after vaccination. Two participants became positive for anti-nuclear antibodies during 6 months' follow-up. There were no sex-dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti-HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.

Objective: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD)., Methods: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated., Results: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future., Conclusions: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal beta2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.

This prospective multicentric register was initiated by the European Forum of Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic committees. This register allows the investigation of infants after written informed parental consent. It collects mothers' clinical pattern of antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and immunological status. For the babies, clinical and immunological examinations are performed at birth; neurodevelopmental conditions followed up to five years. A re-evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies will be done if they are positive at birth to follow their kinetics. A descriptive and a case control study of babies with versus without APL at birth will be possible after the inclusion of 300 cases.

Background: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA)., Objective: To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA)., Methods: Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6-20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE)., Results: Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity., Conclusions: Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.

Objective: Anticardiolipin antibodies (aCL) have been frequently detected in juvenile idiopathic arthritis (JIA), but have not been associated with disease activity or clinical features of the antiphospholipid syndrome (APS). Our aim was to determine aCL and anti-beta2 glycoprotein I (anti-beta2GPI) antibody levels and lupus anticoagulant (LA) in serial samples from children with JIA and to investigate the clinical significance of these antibodies., Methods: The values of aCL, anti-beta2GPI and LA were prospectively followed in 28 children with JIA from disease onset. aCL and anti-beta2GPI were assayed by an ELISA method. Two monoclonal beta2GPI-dependent aCL (HCAL and EY2C9) were used as calibrators. LA was determined by a modified dilute Russell viper venom time test., Results: Thirteen (46.4%) children with JIA were already positive for aCL at their first referral to our center. During the follow-up, the frequency of aCL decreased from 46.4% to 28.6%; however, it remained significantly higher compared with healthy children. In contrast, for anti-beta2GPI the difference in the frequency between the children with JIA and healthy children was not statistically significant. Serial determination of aPL levels in JIA patients revealed frequent fluctuations. Positive aCL persisted over time in 6 (21.4%) children with JIA, 6 (21.4%) children were initially positive for aCL, but became later negative, and 3 (10.7%) children were initially negative for aCL and became later positive. Persistently positive anti-beta2GPI were observed during the follow-up only in one patient, while none of the patients was persistently positive for LA. No association between aCL, anti-beta2GPI or LA and disease activity could be established. No patient with positive aCL, anti-beta2GPI or LA showed any clinical feature of APS., Conclusion: The discrepancy between the presence of aCL and anti-beta2GPI might indicate that the production of aCL in JIA is associated with an infectious trigger. Furthermore, the low frequency of anti-beta2GPI and LA could explain the limited prothrombotic potential of aPL observed in JIA. However, we found a distinct group of JIA patients with persistently positive aCL, the clinical implications of which are at the present time unknown.

Purpose: To measure anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and anti-prothrombin (aPT) antibodies in young patients with epilepsy, and to correlate their presence with demographic data, clinical diagnoses, laboratory and neuroradiologic findings, and antiepileptic drugs (AEDs)., Methods: Sera from one hundred forty-two consecutive patients with epilepsy with a median age of 10 years were tested for aCL and anti-beta2GPI autoantibodies by solid-phase assays. aPT antibodies also were assayed in sera from 90 patients. Positive results were confirmed after a minimum of 6 weeks. Antinuclear antibodies (ANAs) and antibodies against extractable nuclear antigens (ENAs) also were tested., Results: An overall positivity of 41 (28.8%) of 142 sera was found. Fifteen patients were positive for aCL, 25 for anti-beta2GPI, and 18 for aPT antibodies. Several patients (12%) displayed more than one specificity in their serum. Only one of these patients had a concurrent positivity for ANAs and ENAs. A predominance of younger patients was found in the antibody-positive group. All types of epilepsy were represented in the positive group. No relation between antibody positivity and AEDs was found. Diffuse ischemic lesions at computed tomography (CT)/magnetic resonance imaging (MRI) scans were present in higher percentages in patients who were antibody positive. No positive patient had a history of previous thrombosis or other features related to systemic lupus erythematosus (SLE), and no patient was born of a mother with SLE., Conclusions: Our study suggests a relation between epilepsy and aPL in young patients. A pathogenetic role for these autoantibodies cannot be excluded, and their determination might prove useful even from a therapeutic point of view.

In recent years, antiphospholipid antibodies (aPL) and their associated clinical features have been recognized increasingly in various pediatric autoimmune and non-autoimmune diseases. Pathogenic mechanisms involved in pediatric antiphospholipid syndrome (APS) appear to be the same as in adults. However, since pediatric patients do not have prothrombotic risk factors present in adults, there clearly are differences in the spectrum of clinical findings. The frequency of aPL-related thrombotic events is generally low in pediatric populations. On the other hand, various commonly acquired infections are likely to be responsible for higher percentage of non-pathogenic and transient aPL in childhood. Such points have to be considered in clinical judgment of elevated aPL in children. In this review we summarize the recent data on the prevalence and clinical significance of aPL in neonates, children and adolescents.

Objectives: To determine anticardiolipin (aCL) and anti-beta(2) glycoprotein I antibodies (anti-beta(2)GPI) in apparently healthy children and express the cut-off levels in concentrations of monoclonal antibodies, and to compare the mean values and frequencies of aCL and anti-beta(2)GPI in children with those in blood donors., Methods: Blood samples were collected from 29 preschool children and 32 adolescents during their routine preventive follow-up visits. The control group consisted of 52 blood donors. aCL and anti-beta(2)GPI were assayed by an ELISA method. Two monoclonal beta(2)GPI-dependent aCL (HCAL and EY2C9) were used as calibrators., Results: The estimated cut-off values for immunoglobulin G (IgG) and immunoglobulin M (IgM) aCL, expressed in concentrations of monoclonal antibodies and standardized international units (GPL/MPL units), were 13.9 ng/ml (7.6 GPL) and 33.1 ng/ml (3.3 MPL) for preschool children, 13.5 ng/ml (7.2 GPL) and 36.9 ng/ml (4.0 MPL) for adolescents, and 14.4 ng/ml (8.0 GPL) and 42.6 ng/ml (5.1 MPL) for blood donors. No statistically significant differences in the mean values for IgG and IgM aCL were found between the age groups. The mean value of IgA aCL was significantly higher in blood donors than in preschool children and adolescents (P<0.037 and P<0.025 respectively). Seven (11.4%) of 61 apparently healthy children had low positive values for aCL (IgG for all seven). The estimated cut-off values for IgG and IgM anti-beta(2)GPI were 4.2 and 13.1 ng/ml respectively for preschool children, 3.2 and 13.1 ng/ml for adolescents, and 2.9 and 20.5 ng/ml for blood donors. The mean value for IgG anti-beta(2)GPI was found to be higher in preschool children than in adolescents and blood donors (P<0.0001 and P<0.0001). The mean values for IgM and IgA anti-beta(2)GPI were higher in blood donors than in preschool children (IgM, P<0.007; IgA, P<0.0001) and adolescents (IgM, P<0.01; IgA, P<0.0001). Four (6.6%) of 61 apparently healthy children had positive values for anti-beta(2)GPI (two for IgG and two for IgA)., Conclusions: This is the first report in which the cut-off values for aCL and anti-beta(2)GPI in children are expressed in concentrations of monoclonal antibodies. Low titres of aCL, which were identified frequently in apparently healthy children, were hypothesized to be the result of previous infections. The high mean value of IgG anti-beta(2)GPI observed in preschool children was an unexpected result of the study and might indicate a default response to nutritional exposure to beta(2)GPI in this age group.