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.

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 vacination 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 vaccinationinduced autoantibodies in apparently healthy subjects including studies in animals and humans.

The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers (n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers’ diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.

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.

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.

Summary 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-β2-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-β2-GPI IgM was present in three women.These results suggest that aCL and a-β2-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.

OBJECTIVES. The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome. PATIENTS AND METHODS. A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patient's 18th birthday. RESULTS. As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-β2-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. CONCLUSIONS. Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups.

Purpose of reviewAntiphospholipid syndrome is considered as the most common acquired hypercoagulation state of autoimmune disorder in children. Besides vascular occlusion, antiphospholipid antibodies have been associated with various nonthrombotic clinical manifestations. This review highlights recent clinical advances in the field of neonatal and pediatric antiphospholipid syndrome and emphasizes differences in relation to the antiphospholipid syndrome in adult population. Recent findingsNeonatal antiphospholipid syndrome is a rare clinical entity characterized by neonatal thrombotic disease due to the transplacental passage of maternal antiphospholipid antibodies. There is growing evidence that transplacentally transferred antiphospholipid antibodies act as a risk factor, but are not usually a sufficient condition for thrombosis and other thrombophilic risk factors should be systematically evaluated. Long-term studies of children born to antiphospholipid-antibody-positive mothers provided the evidence of possible neurodevelopmental changes in these children and regular neuropsychological assessments are recommended. Data from the pediatric antiphospholipid syndrome studies have confirmed that antiphospholipid-antibody-related thromboses in children are frequently associated with multiple antiphospholipid antibodies positivity and concomitant presence of inherited prothrombotic disorders. Children with antiphospholipid syndrome have frequently demonstrated associated nonthrombotic manifestations, particularly hematological, skin and neurological manifestations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have recognized certain differences that suggest two distinct subgroups with specific clinical characteristics. SummaryClinical and laboratory characterization of pediatric patients with antiphospholipid syndrome continues to improve and implies some important differences between antiphospholipid syndrome in pediatric and adult populations.