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Premature infants are highly susceptible to severe bacterial infections. The impaired infection control related to the functional immaturity of the neonatal innate immune system is an important cause of infection. Different monocyte subpopulations have been described and functionally characterized. However, data from preterm infants are scarce. We analyzed constitutive monocyte TLR2, TLR4, CD163, and HLA-DR expression in preterm cord blood. We further investigated activation of the signaling proteins ERK1/2 and NF-κB in monocyte subpopulations after ex vivo stimulation with the bacterial TLR agonists LPS and lipoteichoic acid. The functional outcome of the stimulation was determined by the intracellular production of TNF. Furthermore, the phagocytic activity was measured via flow cytometry. TLR4 and HLA-DR showed a gestational age-dependent increase. However, activation of ERK1/2 and NF-κB was impaired in neonatal monocyte subpopulations after stimulation with TLR agonists. Accordingly, intracellular TNF was diminished in preterm monocytes, especially in nonclassic monocytes. Premature monocytes showed high phagocytic activity, with significantly lower acidification of the phagosome. The reduced functional response of nonclassic monocytes of preterm neonates appears to be part of the diminished early immune response to bacterial cell wall components and is likely to contribute to their susceptibility to bacterial infection.

The current European Society for Immunodeficiencies (ESID) registry was established 10 years ago in 2004, when the system was moved from a paper-based to an online system. The purpose of the registry is to collect data on European patients with primary immunodeficiencies (PIDs) and their treatment, with the aim of building an easily accessible database for use by physicians and researchers. During the 10 years for which the current registry has been operational, the number of patients registered has grown substantially; after 4 years, more than 7000 patients were registered and, as of 25 June, 19 355 patients are registered in Europe as having a PID. Longitudinal data (20 or more data sets, documented every 6 months) is now available for some of the patients in the registry. Children younger than age 15 years represent two-thirds of this cohort. More than half the patients (57%) have an antibody disorder, and this is also the group with the greatest number of adult patients. Of the 19 355 registered, treatment data are available on approximately 14 000, of whom 6476 receive immunoglobulin (Ig) treatment; 4239 patients are receiving intravenous immunoglobulin (IVIg) treatment and approximately 2181 receive subcutaneous immunoglobulin (SCIg). One of the interesting comparisons arising from the registry data is the difference in minimum prevalence of PIDs between countries. In France, for example, 6·058 cases are documented per 100 000 inhabitants; much higher than in Switzerland (4·157 per 100 000) or Germany (2·105 per 100 000). This is most probably because France has a very efficient documenting system, whereby designated documenters, financed by local grants in France, visit centres to enter patients' data into the registry. Thus, the more efficient the documenting system, the higher the quality of data collected. Physicians and researchers can apply for access to the registry data by writing to ESID with details of their specific project, or with a proposal to collect new and different data on patients with specific diseases. Despite the large number of patients in the registry and the large amount of data collected, only 23 papers have been published, which is an average of more than two per year over 10 years. However, considering that more than 200 physicians and researchers have access to the database, this still means that the registry is one of the most under-used data sets of its kind in Europe. In a recent registry publication we analysed the subset of common variable immunodeficiency (CVID) subjects 1. There are more than 4000 CVID subjects in the registry, but because not all have complete data sets, the cohort described in this paper included 2212 subjects. As CVID has a variable clinical presentation, we investigated the frequencies of different disease phenotypes in the cohort 1. The most common clinical features were pneumonia (32%) and autoimmunity (29%). Other features included splenomegaly (26%), bronchiectasis (23%) and granulomatous disease (10%), and a further 10% had enteropathy. Surprisingly, 5% of patients had solid tumours and 4% had meningitis/encephalitis [conditions associated more usually with X-linked agammaglobulinaemia (XLA)]. Less frequent clinical features were lymphoma, found in 3% of the patients, splenectomy in 2% and lobectomy in 1%. With regard to how efficiently patients are being diagnosed, CVID has been described as having a bi-modal age of manifestation, with a peak in diagnoses between the ages of 5 and 10 years, a trough around the age of 20, and then another peak between 30 and 40 years. However, when patients are asked about the onset of their symptoms the reported age is lower, with most patients experiencing recurrent infections in childhood, and fewer than half manifesting after age 20 (Fig. 1). In some countries, the delay between onset of symptoms and CVID diagnosis is greater than others, the average being 4·1 years, ranging from 1·8 years in Poland to 7 years in France 1. Figure 1 (a) Age at onset of symptoms in the total cohort (n = 1914), among female patients (n = 985) and among male patients (n = 929). (b) Age at diagnosis in the total cohort (n = 2134), among ... We showed that adult CVID cases were diagnosed more promptly than paediatric cases (aged

The European Society for Immunodeficiencies (ESID) Primary Immunodeficiencies Care in Development Working Party was founded in order to improve diagnosis and care of patients with primary immunodeficiencies (PIDs).