The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008

Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Within 4 years, 7430 patients from 39 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity, with 1540 patients or 20.7% of all entries, followed by isolated immunoglobulin (Ig)G subclass deficiency (546 patients, 7.4%). Evaluations show that the average life expectancy for PID patients varies from 1 to 49 years (median), depending on the type of PID. The prevalence and incidence of PID remains a key question to be answered. As the registration progress is far from finished we can only calculate minimum values for PID, with e.g. France currently showing a minimum prevalence of 3.72 patients per 100,000 inhabitants. The most frequently documented permanent treatment is immunoglobulin replacement; 2819 patients (42% of all patients alive) currently receive this form of treatment

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8

Chemokines and Their Role in Parasitic Diseases

Chemotactic cytokines (chemokines), the intercellular mediators, produced and released by a wide variety of cell types, are a group of small secreted proteins (8–10 KDa), which mediate host response to invading organisms (viruses, bacteria, parasites), trauma or tumor. The trafficking, recruiting and recirculation of leukocytes, which is essential in acute and chronic inflammation is controlled by chemokines. This review introduces the three supergene families of chemokines (CXC, CC and C), with emphasis on their adhesion mechanism, biological effects, regulation of expression and critical role in different disease states in humans and in animal models with parasitic diseases

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

none313siBackground: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.noneThalhammer J.; Kindle G.; Nieters A.; Rusch S.; Seppanen M.R.J.; Fischer A.; Grimbacher B.; Edgar D.; Buckland M.; Mahlaoui N.; Ehl S.; Boztug K.; Brunner J.; Demel U.F.; Forster-Waldl E.; Gasteiger L.M.; Goschl L.; Kojic M.; Schroll A.; Seidel M.G.; Wintergerst U.; Wisgrill L.; Sharapova S.O.; Goffard J.-C.; Kerre T.; Meyts I.; Roosens F.; Smet J.; Haerynck F.; Eric Z.P.; Milenova V.; Gagro A.; Richter D.; Chovancova Z.; Hlavackova E.; Litzman J.; Milota T.; Sediva A.; Elaziz D.A.; Alkady R.S.; El Sayed El Hawary R.; Eldash A.S.; Galal N.; Lotfy S.; Meshaal S.S.; Reda S.M.; Sobh A.; Elmarsafy A.; Brosselin P.; Courteille V.; De Vergnes N.; Kracker S.; Pergent M.; Randrianomenjanahary P.; Ahrenstorf G.; Albert M.H.; Ankermann T.; Atschekzei F.; Baumann U.; Becker B.C.; Behrends U.; Belohradsky B.H.; Biegner A.-K.; Binder N.; Bode S.F.N.; Boesecke C.; Boetticher B.; Borte M.; Borte S.; Classen C.F.; Dirks J.; Duckers G.; El-Helou S.; Ernst D.; Fasshauer M.; Fecker G.; Felgentreff K.; Foell D.; Ghosh S.; Girschick H.J.; Goldacker S.; Graf N.; Graf D.; Greil J.; Hanitsch L.G.; Hauck F.; Heeg M.; Heine S.I.; Henes J.C.; Hoenig M.; Holzer U.; Holzinger D.; Horneff G.; Hundsdoerfer P.; Jablonka A.; Jakoby D.; Joean O.; Kaiser-Labusch P.; Klemann C.; Kobbe R.; Korholz J.; Kramm C.M.; Kruger R.; Landwehr-Kenzel S.; Lehmberg K.; Liese J.G.; Lippert C.F.; Maccari M.E.; Masjosthusmann K.; Meinhardt A.; Metzler M.; Morbach H.; Muller I.; Naumann-Bartsch N.; Neubert J.; Niehues T.; Peter H.-H.; Rieber N.; Ritterbusch H.; Rockstroh J.K.; Roesler J.; Schauer U.; Scheible R.; Schmalzing M.; Schmidt R.E.; Schneider D.T.; Schreiber S.; Schuetz C.; Schulz A.; Schulze-Koops H.; Schulze-Sturm U.; Schuster V.; Schwaneck E.C.; Schwarz K.; Schwarze-Zander C.; Sirin M.; Skapenko A.; Sogkas G.; Sparber-Sauer M.; Speckmann C.; Steinmann S.; Stiehler S.; Tenbrock K.; von Bernuth H.; Warnatz K.; Wasmuth J.-C.; Weiss M.; Witte T.; Wittke K.; Wittkowski H.; Zeuner R.A.; Farmaki E.; Hatzistilianou M.N.; Kakkas I.; Kanariou M.G.; Kapousouzi A.; Liatsis E.; Maggina P.; Papadopoulou-Alataki E.; Raptaki M.; Speletas M.; Tantou S.; Goda V.; Krivan G.; Marodi L.; Abolhassani H.; Aghamohammadi A.; Rezaei N.; Feighery C.; Leahy T.R.; Ryan P.; Batzir N.A.; Garty B.Z.; Tamary H.; Aiuti A.; Amodio D.; Azzari C.; Barzaghi F.; Baselli L.A.; Cancrini C.; Carrabba M.; Cazzaniga M.; Cesaro S.; Chinello M.; Danieli M.G.; Dellepiane R.M.; Fabio G.; Gambineri E.; Lodi L.; Lougaris V.; Marasco C.; Martire B.; Marzollo A.; Milito C.; Moschese V.; Pignata C.; Plebani A.; Porta F.; Quinti I.; Ricci S.; Soresina A.; Tommasini A.; Vacca A.; Vanessa C.; Blaziene A.; Sitkauskiene B.; Gowin E.; Heropolitanska-Pliszka E.; Pietrucha B.; Szaflarska A.; Wiesik-Szewczyk E.; Wolska-Kusnierz B.; Esteves I.; Faria E.; Marques L.H.; Neves J.F.; Silva S.L.; Teixeira C.; Pereira da Silva S.; Capilna B.R.; Guseva M.N.; Shcherbina A.; Bobcakova A.; Ciznar P.; Gabzdilova J.; Jesenak M.; Kapustova L.; Orosova J.; Petrovicova O.; Raffac S.; Kopac P.; Allende L.M.; Antoli A.; Blanch G.R.; Carbone J.; Dieli-Crimi R.; Garcia-Prat M.; Gil-Herrera J.; Gonzalez-Granado L.I.; Agullo P.L.; Olbrich P.; Parra-Martinez A.; Paz-Artal E.; Pleguezuelo D.E.; Rodriguez N.S.; Sanchez-Ramon S.; Santos-Perez J.L.; Solanich X.; Soler-Palacin P.; Gonzalez-Amores M.; Ekwall O.; Fasth A.; Bitzenhofer-Gruber M.; Candotti F.; Dimitriou F.; Heininger U.; Holbro A.; Jandus P.; Kolios A.G.A.; Marschall K.; Schmid J.P.; Posfay-Barbe K.M.; Prader S.; Reichenbach J.; Steiner U.C.; Truck J.; Bredius R.G.; de Kruijf- Bazen S.; de Vries E.; Henriet S.S.V.; Kuijpers T.W.; Potjewijd J.; Rutgers A.; Stol K.; van Aerde K.J.; Van den Berg J.M.; van de Ven A.A.J.M.; Montfrans J.; Aydemir S.; Baris S.; Dogu F.; Ikinciogullari A.; Karakoc-Aydiner E.; Kilic S.S.; Kiykim A.; Kokcu Karadag S.I.; Kutukculer N.; Ocak S.; UNAL E.; Boyarchuk O.; Hilfanova A.; Kostyuchenko L.V.; Alachkar H.; Arkwright P.D.; Baxendale H.E.; Bernatoniene J.; Coulter T.I.; Garcez T.; Goddard S.; Gompels M.M.; Grigoriadou S.; Herriot R.; Herwadkar A.; Huissoon A.; Ibberson L.; Nademi Z.; Noorani S.; Parvin S.; Steele C.L.; Thomas M.; Waruiru C.; Yong P.F.K.; Bourne H.Thalhammer, J.; Kindle, G.; Nieters, A.; Rusch, S.; Seppanen, M. R. J.; Fischer, A.; Grimbacher, B.; Edgar, D.; Buckland, M.; Mahlaoui, N.; Ehl, S.; Boztug, K.; Brunner, J.; Demel, U. F.; Forster-Waldl, E.; Gasteiger, L. M.; Goschl, L.; Kojic, M.; Schroll, A.; Seidel, M. G.; Wintergerst, U.; Wisgrill, L.; Sharapova, S. O.; Goffard, J. -C.; Kerre, T.; Meyts, I.; Roosens, F.; Smet, J.; Haerynck, F.; Eric, Z. P.; Milenova, V.; Gagro, A.; Richter, D.; Chovancova, Z.; Hlavackova, E.; Litzman, J.; Milota, T.; Sediva, A.; Elaziz, D. A.; Alkady, R. S.; El Sayed El Hawary, R.; Eldash, A. S.; Galal, N.; Lotfy, S.; Meshaal, S. S.; Reda, S. M.; Sobh, A.; Elmarsafy, A.; Brosselin, P.; Courteille, V.; De Vergnes, N.; Kracker, S.; Pergent, M.; Randrianomenjanahary, P.; Ahrenstorf, G.; Albert, M. H.; Ankermann, T.; Atschekzei, F.; Baumann, U.; Becker, B. C.; Behrends, U.; Belohradsky, B. H.; Biegner, A. -K.; Binder, N.; Bode, S. F. N.; Boesecke, C.; Boetticher, B.; Borte, M.; Borte, S.; Classen, C. F.; Dirks, J.; Duckers, G.; El-Helou, S.; Ernst, D.; Fasshauer, M.; Fecker, G.; Felgentreff, K.; Foell, D.; Ghosh, S.; Girschick, H. J.; Goldacker, S.; Graf, N.; Graf, D.; Greil, J.; Hanitsch, L. G.; Hauck, F.; Heeg, M.; Heine, S. I.; Henes, J. C.; Hoenig, M.; Holzer, U.; Holzinger, D.; Horneff, G.; Hundsdoerfer, P.; Jablonka, A.; Jakoby, D.; Joean, O.; Kaiser-Labusch, P.; Klemann, C.; Kobbe, R.; Korholz, J.; Kramm, C. M.; Kruger, R.; Landwehr-Kenzel, S.; Lehmberg, K.; Liese, J. G.; Lippert, C. F.; Maccari, M. E.; Masjosthusmann, K.; Meinhardt, A.; Metzler, M.; Morbach, H.; Muller, I.; Naumann-Bartsch, N.; Neubert, J.; Niehues, T.; Peter, H. -H.; Rieber, N.; Ritterbusch, H.; Rockstroh, J. K.; Roesler, J.; Schauer, U.; Scheible, R.; Schmalzing, M.; Schmidt, R. E.; Schneider, D. T.; Schreiber, S.; Schuetz, C.; Schulz, A.; Schulze-Koops, H.; Schulze-Sturm, U.; Schuster, V.; Schwaneck, E. C.; Schwarz, K.; Schwarze-Zander, C.; Sirin, M.; Skapenko, A.; Sogkas, G.; Sparber-Sauer, M.; Speckmann, C.; Steinmann, S.; Stiehler, S.; Tenbrock, K.; von Bernuth, H.; Warnatz, K.; Wasmuth, J. -C.; Weiss, M.; Witte, T.; Wittke, K.; Wittkowski, H.; Zeuner, R. A.; Farmaki, E.; Hatzistilianou, M. N.; Kakkas, I.; Kanariou, M. G.; Kapousouzi, A.; Liatsis, E.; Maggina, P.; Papadopoulou-Alataki, E.; Raptaki, M.; Speletas, M.; Tantou, S.; Goda, V.; Krivan, G.; Marodi, L.; Abolhassani, H.; Aghamohammadi, A.; Rezaei, N.; Feighery, C.; Leahy, T. R.; Ryan, P.; Batzir, N. A.; Garty, B. Z.; Tamary, H.; Aiuti, A.; Amodio, D.; Azzari, C.; Barzaghi, F.; Baselli, L. A.; Cancrini, C.; Carrabba, M.; Cazzaniga, M.; Cesaro, S.; Chinello, M.; Danieli, M. G.; Dellepiane, R. M.; Fabio, G.; Gambineri, E.; Lodi, L.; Lougaris, V.; Marasco, C.; Martire, B.; Marzollo, A.; Milito, C.; Moschese, V.; Pignata, C.; Plebani, A.; Porta, F.; Quinti, I.; Ricci, S.; Soresina, A.; Tommasini, A.; Vacca, A.; Vanessa, C.; Blaziene, A.; Sitkauskiene, B.; Gowin, E.; Heropolitanska-Pliszka, E.; Pietrucha, B.; Szaflarska, A.; Wiesik-Szewczyk, E.; Wolska-Kusnierz, B.; Esteves, I.; Faria, E.; Marques, L. H.; Neves, J. F.; Silva, S. L.; Teixeira, C.; Pereira da Silva, S.; Capilna, B. R.; Guseva, M. N.; Shcherbina, A.; Bobcakova, A.; Ciznar, P.; Gabzdilova, J.; Jesenak, M.; Kapustova, L.; Orosova, J.; Petrovicova, O.; Raffac, S.; Kopac, P.; Allende, L. M.; Antoli, A.; Blanch, G. R.; Carbone, J.; Dieli-Crimi, R.; Garcia-Prat, M.; Gil-Herrera, J.; Gonzalez-Granado, L. I.; Agullo, P. L.; Olbrich, P.; Parra-Martinez, A.; Paz-Artal, E.; Pleguezuelo, D. E.; Rodriguez, N. S.; Sanchez-Ramon, S.; Santos-Perez, J. L.; Solanich, X.; Soler-Palacin, P.; Gonzalez-Amores, M.; Ekwall, O.; Fasth, A.; Bitzenhofer-Gruber, M.; Candotti, F.; Dimitriou, F.; Heininger, U.; Holbro, A.; Jandus, P.; Kolios, A. G. A.; Marschall, K.; Schmid, J. P.; Posfay-Barbe, K. M.; Prader, S.; Reichenbach, J.; Steiner, U. C.; Truck, J.; Bredius, R. G.; de Kruijf- Bazen, S.; de Vries, E.; Henriet, S. S. V.; Kuijpers, T. W.; Potjewijd, J.; Rutgers, A.; Stol, K.; van Aerde, K. J.; Van den Berg, J. M.; van de Ven, A. A. J. M.; Montfrans, J.; Aydemir, S.; Baris, S.; Dogu, F.; Ikinciogullari, A.; Karakoc-Aydiner, E.; Kilic, S. S.; Kiykim, A.; Kokcu Karadag, S. I.; Kutukculer, N.; Ocak, S.; Unal, E.; Boyarchuk, O.; Hilfanova, A.; Kostyuchenko, L. V.; Alachkar, H.; Arkwright, P. D.; Baxendale, H. E.; Bernatoniene, J.; Coulter, T. I.; Garcez, T.; Goddard, S.; Gompels, M. M.; Grigoriadou, S.; Herriot, R.; Herwadkar, A.; Huissoon, A.; Ibberson, L.; Nademi, Z.; Noorani, S.; Parvin, S.; Steele, C. L.; Thomas, M.; Waruiru, C.; Yong, P. F. K.; Bourne, H