Vaccinating an Immunocompromised Child

Any illness associated with possible immune dysfunction during childhood requires a decision on the start and/or continuation of ongoing vaccination program according to national guidelines, as well as the decision on possible booster vaccination and vaccination with additional, registered vaccines. It is widely accepted that if a child with presumed or proven immune disorder might benefit from vaccination, this should not be delayed if its application is safe. Children with immune disorders vary in the degree of immunosuppression, susceptibility to infections and immune reactions after vaccination. Besides these, there are certain groups of children with diseases that increase their risk of infectious diseases even in the absence of specific immune disorders. In this article, we discuss the basic principles that should guide decisions for immunization of children with suspected or proven immune system disorder (primary or secondary)

AUTOIMMUNITY AND IMMUNODEFICIENCIES

Zajedničko obilježje patogeneze autoimunosnih bolesti i primarnih imunodefi cijencija (PID) jest poremećaj imunosustava. Tradicionalno se većina autoimunosnih bolesti smatrala poligenski uvjetovanima, no u posljednjih desetak godina otkriveno je da i mutacije pojedinačnih gena za različite čimbenike ključne za funkciju imunosustava mogu dovesti do različitih autoimunosnih manifestacija. Tim spoznajama otvoren je novi način razmišljanja o autoimunosnim bolestima i njihovom preklapanju s primarnim imunodefi cijencijama. Način kako poremećaj jednoga gena dovodi do nastanka autoimunosne bolesti nije za svaki od njih poznat, a valja vidjeti i postoji li preklapanje autoimunosnih bolesti s imunodefi cijencijom. Cilj je ovoga kratkog preglednog članka opisati učestalost, kliničku prezentaciju i moguće mehanizme autoimunosnih manifestacija u bolesnika s primarnim imunodefi cijencijama koji mogu biti korisni za reumatologe.Autoimmune diseases and primary immunodefi ciencies share a common pathogenesis characterized by dysregulation of immunity. Although most autoimmune diseases show a polygenic inheritance pattern, it has been shown that monogenic defects of various immune system components could lead to autoimmunity as well. Th ese fi ndings have opened a new pathway for understanding the development of autoimmune diseases and the overlap between immunodefi ciency and autoimmunity. Th e mechanism of how a single gene defect leads to autoimmunity is not completely known. Th e purpose of this clinically-oriented review is to describe the incidence, clinical presentation, and possible mechanisms of autoimmunity in patients with primary immunodefi ciencies relevant to rheumatologists

Characteristics of Immune Reactions in Respiratory Infections

Imunoreakcija u respiratornoj infekciji mora biti brza i učinkovita u prevenciji infekcija koje su potencijalno letalnog ishoda. Međutim, pretjerana i neadekvatna upalna i imunosna reakcija može značajno oštetiti tkivo pluća i poremetiti respiracijsku funkciju. Prvu liniju obrane čine mukus i trepetljike respiratornog epitela, a zatim medijatori koji predstavljaju prirođenu imunost. Ti medijatori (npr. laktoferin, lizozim, kolektini i defenzini) mogu direktno lizirati mikroorganizme ili ih uništiti opsonizacijom i mobilizacijom upalnih stanica. Specifi čna imunost uključuje lučenje antitijela i T-limfocite. Različite podgrupe T-limfocita koji izlučuju Th1 ili Th2-tipične citokine mogu značajno utjecati na odstranjenje mikroorganizma u plućima i inducirati oštećenje tkiva ovisno o vrsti citokina koje izlučuju.The immune response to respiratory infection must be rapid and effi cient in preventing those with a potential lethal outcome. However, the excessive or inappropriate infl ammatory and immune responses could lead to destruction of lung tissue thus grossly affecting respiratory function. The fi rst line of defence comes from barriers such as mucus and cilia, followed by mediators that constitute the innate response. Activation of these mediators (i.e. lactoferrin, lysozyme, collectins and defensins) can lead directly to lysis of pathogens, or to destruction through opsonisation or the recruitment of infl ammatory cells. The adaptive immune response includes the production of antibodies and the responses of T lymphocytes. Different subsets of T lymphocytes secreting Th1- or Th2-associated cytokines may dramatically alter the balance between clearance of the pathogen from the lung and induction of tissue damage depending on the cytokines they secrete

Suvremene spoznaje u imunologiji i njihova primjena u kliničkoj alergologiji

The objective of this review is to present some novel concepts in the field of immunology that help us understand the pathophysiological mechanisms of allergic diseases. The recognition of their heterogeneous nature in combination with animal models and sophisticated in vitro immunologic methods should help us translate these findings to clinical practice in order to upgrade the prevention, diagnosis and treatment of allergic diseases.U ovom revijskom prikazu namjera je prikazati neke nove spoznaje iz područja imunologije koja su pomogla razumijevanju patofizioloških mehanizama alergijskih bolesti. Prepoznavanjem složene naravi tih bolesti i uporabom životinjskih modela te suvremenih imunoloških metoda istraživanja in vitro nastoji se iste rabiti u rutinskom kliničkom radu u svrhu uspješnije prevencije, dijagnostike i liječenja alergijskih bolesti

Characteristics of Immune Reactions in Respiratory Infections

Imunoreakcija u respiratornoj infekciji mora biti brza i učinkovita u prevenciji infekcija koje su potencijalno letalnog ishoda. Međutim, pretjerana i neadekvatna upalna i imunosna reakcija može značajno oštetiti tkivo pluća i poremetiti respiracijsku funkciju. Prvu liniju obrane čine mukus i trepetljike respiratornog epitela, a zatim medijatori koji predstavljaju prirođenu imunost. Ti medijatori (npr. laktoferin, lizozim, kolektini i defenzini) mogu direktno lizirati mikroorganizme ili ih uništiti opsonizacijom i mobilizacijom upalnih stanica. Specifi čna imunost uključuje lučenje antitijela i T-limfocite. Različite podgrupe T-limfocita koji izlučuju Th1 ili Th2-tipične citokine mogu značajno utjecati na odstranjenje mikroorganizma u plućima i inducirati oštećenje tkiva ovisno o vrsti citokina koje izlučuju.The immune response to respiratory infection must be rapid and effi cient in preventing those with a potential lethal outcome. However, the excessive or inappropriate infl ammatory and immune responses could lead to destruction of lung tissue thus grossly affecting respiratory function. The fi rst line of defence comes from barriers such as mucus and cilia, followed by mediators that constitute the innate response. Activation of these mediators (i.e. lactoferrin, lysozyme, collectins and defensins) can lead directly to lysis of pathogens, or to destruction through opsonisation or the recruitment of infl ammatory cells. The adaptive immune response includes the production of antibodies and the responses of T lymphocytes. Different subsets of T lymphocytes secreting Th1- or Th2-associated cytokines may dramatically alter the balance between clearance of the pathogen from the lung and induction of tissue damage depending on the cytokines they secrete

ASTHMA IN CHILDREN

Astma je najčešća kronična bolest u djece koju obilježava dugotrajna upala dišnih putova promjenjivog intenziteta praćena spontanom ili lijekovima reverzibilnom akutnom bronhokonstrikcijom. Nastanak astme, težina kliničke slike i učinak terapije određeni su brojnim genetskim i okolišnim čimbenicima. Astma se u djece odlikuje izrazitom heterogenošću s obzirom na moguću etiologiju, stupanj upale i oštećenja bronha, poremećaja funkcije pluća i posljedičnu kliničku prezentaciju kao i prirodan tijek bolesti koji se u nekih nastavlja i u odrasloj dobi. Opisani su i brojni čimbenici koji prisutni u ranom životu djeluju zaštitno na razvoj astme. Dosadašnje spoznaje o patofiziološkim mehanizmima alergijske reakcije kao bolesti najčešće posredovanoj Th2-limfocitima ne objašnjavaju tu heterogenost pa se u zadnjih nekoliko godina o astmi govori kao sindromu s više različitih podtipova ili endotipova definiranih novodefiniranim imunopatofiziološkim mehanizmima. Pravodobna dijagnoza i odgovarajuće liječenje preduvjet su za sprječavanje ireverzibilnih promjena dišnih putova i posljedičnog slabljenja plućne funkcije.Asthma is the most common chronic disease in childhood characterized by chronic bronchial inflammation of variable intensity accompanied by spontaneous or drug reversible airflow obstruction. The onset of asthma, clinical presentation and response to therapy are influenced by numerous genetic and environmental factors. Asthma in childhood is characterized by its heterogeneity in terms of possible etiology, degree of inflammation and airway obstruction, lung function as well as the natural course of disease that may persist and continue to adulthood. Protective factors linked to early life experiences have also been delineated which may impact the development of asthma. Pathophysiological mechanisms of allergic reaction as an excessive inflammation driven by T-helper-2 (Th2) immunity, offer poor understanding of the heterogeneity of clinical disease. A recently introduced approach defines asthma as a syndrome that comprises of several subtypes or endotypes based on entirely novel pathways to disease. Timely diagnosis and adequate treatment are necessary to prevent irreversible airway remodeling and consequent decrease in pulmonary function

ASTHMA IN CHILDREN

Astma je najčešća kronična bolest u djece koju obilježava dugotrajna upala dišnih putova promjenjivog intenziteta praćena spontanom ili lijekovima reverzibilnom akutnom bronhokonstrikcijom. Nastanak astme, težina kliničke slike i učinak terapije određeni su brojnim genetskim i okolišnim čimbenicima. Astma se u djece odlikuje izrazitom heterogenošću s obzirom na moguću etiologiju, stupanj upale i oštećenja bronha, poremećaja funkcije pluća i posljedičnu kliničku prezentaciju kao i prirodan tijek bolesti koji se u nekih nastavlja i u odrasloj dobi. Opisani su i brojni čimbenici koji prisutni u ranom životu djeluju zaštitno na razvoj astme. Dosadašnje spoznaje o patofiziološkim mehanizmima alergijske reakcije kao bolesti najčešće posredovanoj Th2-limfocitima ne objašnjavaju tu heterogenost pa se u zadnjih nekoliko godina o astmi govori kao sindromu s više različitih podtipova ili endotipova definiranih novodefiniranim imunopatofiziološkim mehanizmima. Pravodobna dijagnoza i odgovarajuće liječenje preduvjet su za sprječavanje ireverzibilnih promjena dišnih putova i posljedičnog slabljenja plućne funkcije.Asthma is the most common chronic disease in childhood characterized by chronic bronchial inflammation of variable intensity accompanied by spontaneous or drug reversible airflow obstruction. The onset of asthma, clinical presentation and response to therapy are influenced by numerous genetic and environmental factors. Asthma in childhood is characterized by its heterogeneity in terms of possible etiology, degree of inflammation and airway obstruction, lung function as well as the natural course of disease that may persist and continue to adulthood. Protective factors linked to early life experiences have also been delineated which may impact the development of asthma. Pathophysiological mechanisms of allergic reaction as an excessive inflammation driven by T-helper-2 (Th2) immunity, offer poor understanding of the heterogeneity of clinical disease. A recently introduced approach defines asthma as a syndrome that comprises of several subtypes or endotypes based on entirely novel pathways to disease. Timely diagnosis and adequate treatment are necessary to prevent irreversible airway remodeling and consequent decrease in pulmonary function

Therapeutic Effect of Amniotic Membrane in Persistent Epithelial Defects and Corneal Ulcers in Herpetic Keratitis

Amniotic membrane transplantation (AMT) promotes rapid epithelialization and reduces stromal inflammation and ulceration in HSV-1 keratitis. 18 patients with non-healing epithelial defect or corneal ulcer caused by herpetic keratitis were included in the study. All patients were treated by AMT. Corneal epithelial cells in patients suffering from herpetic keratitis secreted 5 ± 4.8 pg/ml of IL-1a and 0.16 ± 0.47 pg/ml of IL-1b (mean ± SD). IL-1a level was significantly higher as compared to controls (p<0.005). Amniotic membranes that were used to treat investigated patients contained 339.87 ± 105 pg/ml of IL-1ra. In herpetic keratitis pro-inflammatory cytokine IL-1a is secreted from corneal epithelial cells in significantly higher level then in controls. Beneficial effect of the AMT in such patients could be explained by the fact that AM secretes its natural antagonist IL-1ra

Therapeutic Effect of Amniotic Membrane in Persistent Epithelial Defects and Corneal Ulcers in Herpetic Keratitis

Amniotic membrane transplantation (AMT) promotes rapid epithelialization and reduces stromal inflammation and ulceration in HSV-1 keratitis. 18 patients with non-healing epithelial defect or corneal ulcer caused by herpetic keratitis were included in the study. All patients were treated by AMT. Corneal epithelial cells in patients suffering from herpetic keratitis secreted 5 ± 4.8 pg/ml of IL-1a and 0.16 ± 0.47 pg/ml of IL-1b (mean ± SD). IL-1a level was significantly higher as compared to controls (p<0.005). Amniotic membranes that were used to treat investigated patients contained 339.87 ± 105 pg/ml of IL-1ra. In herpetic keratitis pro-inflammatory cytokine IL-1a is secreted from corneal epithelial cells in significantly higher level then in controls. Beneficial effect of the AMT in such patients could be explained by the fact that AM secretes its natural antagonist IL-1ra

Serum Immune Markers Differentiation in Patients With Puumala or Dobrava Virus Infections

Hemorrhagic fever with renal syndrome (HFRS) is widely distributed in Europe and caused mostly by two different orthohantaviruses: Puumala virus (PUUV) and Dobrava virus (DOBV). Several studies have implicated that HFRS is an immunologically mediated disease and that the proinflammatory cytokines may have a role in the immunopathogenesis of HFRS. In this study, we have detected: IL-2; IL-6; their soluble receptors (sIL-2R, sIL-6R); TNF-alpha; sCD23; and total IgE in two consecutive sera of HFRS patients, and have looked for their possible relation with the main blood and biochemical findings in order to determine their possible role in disease progression. The differences in the level of measured parameters between PUUV- and DOBV-infected patients were also observed. The sIL-2R, sIL-6R and sCD23 levels were elevated in all HFRS patients, but we did not find any statistical difference between 1st and 2nd sera. The total IgE was elevated in about 1/3 of HFRS patients in both sera. We detected higher IL-6, sIL-2R and sCD23 levels in the sera of patients with DOBV infection than in patients with PUUV infection, with no statistically significant difference. The total IgE level was elevated in five of the six tested patients with DOBV infection, and they had a statistically higher level of total IgE than patients with PUUV infection. Almost all the listed biochemical and blood parameters in HFRS patients stand either in positive or in negative correlation with sIL-2Rapha. The levels of urea and creatinine, which are the hallmarks of HFRS severity, stand in positive correlation with sIL-2Rapha, IL-6, sIL-6R and sCD23. The level of the total IgE stands either in positive or in negative correlation with proteins and parameters of the liver function. We have also found a high positive correlation between the total IgE level and basophile count