Secondary Immune Deficiency Research Articles

Stroke in a young adult receiving intravenous immunoglobulin therapy for immune thrombocytopenic purpura

Intravenous immunoglobulin (IVIG) is increasingly being used in wide variety of auto-immune and inflammatory disorders. FDA has approved the use of IVIG in primary and secondary immune-deficiencies like Chronic Lymphoid leukemia, HIV infection, prevention of GVHD in bone marrow transplantation, ITP, Polymyositis and Kawasaki's disease, pemphigus vulgaris and Guillain barre syndrome and many other disorders.(1). Although they are generally considered safe however, thrombotic complications are being recognized more often in recent years including arterial and venous thrombosis after being used in wide range and extended spectrum of disorders, (2). We report a case of thrombotic stroke in a young adult patient who received IVIG for acute ITP and had no underlying risk factors for development of stroke.

Immune Modulation in Children. A South African Perspective

Immune deficiencies in South Africa can be divided into two categories, i.e. primary immune deficiencies or secondary due to illnesses such as malignancies or infection e.g. the human immune virus (HIV). In the private pediatric clinical setting, children of-ten present with illnesses that can be traced to selective secondary immune deficiencies. Although highly effective, not all children are eligible for intravenous immunoglobulin therapy, either due to costs or non-IgG related immune deficiencies such as selective IgA or T-cell deficiencies. Intramuscular and subdermal immunoglobulin options are equally expensive and uncomfortable. The use of oral immune modulators, such as the erythromycin derivatives, has raised some concern, mainly because of the potential risk of bacterial resistance. Other so called immune boosters, e.g. Echinacea’s, are being advertised as potential solutions but have yet to prove to be efficient. In addition to this, the interaction between the gut micro-biome and the immune system is complex, but critical in maintaining and optimizing the immune system. Under certain disease entities such as inflammatory bowel disease, resulting in a leaky gut, the immune system becomes compromised because of the interaction between certain inflammatory signals and the lymphoid and bone marrow tissue specifically the naive and memory T-cell populations, such as CD4 and CD8 lymphocytes. An overview to immune modulation will be presented that has a direct beneficial effect on the health outcome of the children and new therapeutic modalities will be evaluated in terms of their response and restoration of the T-cell populations.

IMMUNOMODULATORY THERAPY IN PATIENTS WITH UPPER RESPIRATORY TRACT INFECTIONS AND UPPER RESPIRATORY TRACT

Acute respiratory infections remain one of the most pressing health issues in our society, they form a high fraction of all infectious disease cases, and they pose a high risk of complications, among others these can affect upper respiratory tract (acute otitis media, evstaheit etc.), or exacerbate chronic diseases like chronic tonsilitis, and adenoiditis. Many patients have signs of secondary immune deficiency. In these cases affection of the upper respiratory tract is lingering with frequent relapses, and standard therapy is less effective. Supplementing the treatment regime with advanced immunomodulatory drug polyoksidonii reduces the treatment time for both acute inflammation of upper respiratory tract, and for exacerbation of chronic ENT pathology. It can also reduce the number of relapses during remission. A variety of forms and dosages provides the easy of use. Results of clinical studies confirm the high efficacy and safety.

Clinical and immunological characteristics of bronchial asthma phenotype with syndrome of secondary immune deficiency

Background, To study the clinical and immunological features of the phenotype of bronchial asthma with syndrome of secondary immune deficiency. Methods, The analysis of observation of 105 patients with bronchial asthma (BA) was conducted, 70 patients had a clinical markers of secondary immune deficiency. Results, Patients suffering from BA with secondary immune deficiency were observed, there was inhibition of cellular and phagocytic links on the background of activation of the humoral immune system. Changes in immune status were recorded on the clinical course of the disease. Conclusion, BA patients with a concomitant syndrome of secondary immune deficiency had heterogeneous disorders of the immune system, leading to clinical manifestations of secondary immune deficiency, making it difficult for bronchial asthma, contributes to chronic foci of infection, refractoriness to traditional treatment methods.

Impact of Low Immunoglobulin Levels on Disease Outcomes of IBD

Introduction: Inflammatory bowel disorders (IBD) have been considered immune-mediated disorders with dysregulated innate and adaptive immunities. However, the treatment failure of immunosuppressive agents is common. One theory behind this failure is secondary humoral and/or cellular immune deficiency. There remains a lack of investigation into quantifiable clinical outcomes of patients with IBD in the setting of low Ig levels. We aimed to identify an association between low Ig levels in IBD patients and poor clinical outcomes. Methods: A case-controlled analysis was performed on subjects with Crohn's disease (CD) and ulcerative colitis (UC) with measured IgG and IgG1 levels obtained from April 2002 through December 2014. Exclusion criteria included those with known primary immunodeficiency disorder and those with HIV. Poor disease outcomes were defined primarily as the need for IBD-related bowel resection or nonsurgical IBD-related hospitalizations following documented Ig levels. Other outcomes measured included C. difficile/CMV infection and any escalation of the patient's prior drug regimen. Demographic and clinical characteristics were measured, and univariate and multivariate analyses were performed. Results: A total of 82 IBD patients (50% female, 20 with UC and 62 with CD) had documented IgG/G1 levels. 27 (33%) had normal IgG/G1 levels and 55 (67%) had a deficiency. 15 (55.6%) patients with normal Ig levels were found to have poor clinical outcomes defined as documented IBD-related surgery or hospitalization, while 38 (69.1%) patients with low levels experienced poor outcomes (p=0.23). All 8 patients requiring small bowel resection had IgG/G1 deficiency (p=0.048). Risk factors associated with poor outcomes included immunomodulator use (p=0.008), regular antibiotic use (p=0.042), elevated hgb and albumin levels (p=0.002, p=0.001), and number of hospitalizations prior to levels (p < 0.001). In the MV analysis, risk factors associated with poor outcomes included increased hospitalizations prior to drawn levels (OR=1.5, p=0.029). Other trends included an increased albumin level (OR=0.52, p=0.097), immunomodulator use (OR=5.91, p=0.12), and IgG/G1 deficiency (OR=1.5, p=0.69). Conclusion: Our study demonstrated a trend towards poor clinical outcomes in IBD patients with lower Ig levels. This suggests that boosting humoral immunity might be beneficial for select IBD patients. This, in turn, suggests clinical implications for future treatment options in this patient subset.Figure 1Figure 2Figure 3

Vaccination in patients with primary immune deficiency, secondary immune deficiency and autoimmunity with immune regulatory abnormalities.

Vaccination has been an important healthcare measure in preventing infectious diseases. The response to vaccination is reduced in immunocompromised patients, primary immune deficiency (PID) and secondary immune deficiency (SID), but vaccination studies still demonstrated a protective effect resulting in reducing complications, hospitalization, treatment costs and even mortality. The primary physician and the specialist directing patient care are responsible for vaccination. Live vaccines are contraindicated in patients with severe immune impairment, killed vaccines are highly recommended in PID and SID. Criteria have been defined to distinguish high- or low-level immune impairment in the different disease entities among PID and SID patients. For patients who do not respond to diagnostic vaccination as characterized by antibody failure immunoglobulin replacement is the mainstay of therapy.

Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural empyema and bacteremia

Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and <2 years or >65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections and nasopharyngeal carriage studies. The first case of this report was presented because of an IPD with a serotype included in PCV13 implemented in the routine childhood vaccination schedule and to give an idea about pneumococcal strains circulating in the community. The second case was discussed to draw attention for the evaluation of immune deficiencies and other risk factors in recurrent infections with encapsulated bacteria such as pneumococci. Pneumococcal conjugate vaccines contribute the public immunity with the reduction of vaccine-type pneumococcal nasopharyngeal carriage, IPD incidence, and IPD associated morbidity and mortality especially in young children, at the same time cause a decrease in the prevalence of antibiotic-resistant infections. Application of the pneumococcal conjugate vaccines covering the whole society is important, according to all these important results.

Attitude, knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency

BackgroundImmunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. MethodsAn anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression. ResultsAmong the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57–60]) against seasonal influenza and 49% (95%CI [47–50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated. ConclusionDespite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.

Clinical and Immunological Evaluation of Application of Ronkoleukin in Nonspecific Vulvovaginitis at Adolescent Girls

Package Insert: According to immunological parameters there was found that during the sub-acute there is the secondary immune deficiency and the immunodeficiency is absent during the acute. During the acute phagocytic function of the local secret is satisfactory, and during the sub-acute against satisfactory absorption function there is a decrease of bacterial growth-inhibitory activity of vaginal secretions, indicating the necessity of correction of phagocytic component of these patients. The Purpose of the Research: Clinical and immunological evaluation of ronkoleukin using depending on the routes of entry in the treatment of non-specific vulvovaginitis among adolescent girls in different variants of the disease state. Design of their Search: Prospective study. Methodology: From 2006 to 2010 years by the assignment of adolescent therapist and upon periodic screening the adolescent girls with a variety of complains for genitalia were examined in the child and adolescent consulting room in Municipal Polyclinic No 11 and «The City Center of Human Original Research Article Kenzhebekovna and Medeubaevna; BJMMR, 10(8): 1-12, 2015; Article no.BJMMR.18891 2 Reproduction» in Almaty. 124 menstruate adolescent girls from 11 to 18 years, not sexually active, were selected to accomplish the target objective. I group -20 healthy (control). II group 62 with per-acute nonspecific vulvovaginitis. III group 42 with sub-acute nonspecific vulvovaginitis. In cooperation with the scientific consultant and immunologist, M.D. Prof. A. Kurmanova there was developed a dosage schedule of roncoleukine in the complex therapy, based on the results of the analyses of the immune and cytokine status and phagocytic vaginal system. II group 62 patients with per-acute nonspecific vulvovaginitis. II А– 20 patients with sub-acute nonspecific vulvovaginitis. (Standard therapy + roncoleukine 250 000 U/ml vaginal irrigation once a day). II B– 25 adolescent girls with sub-acute. (Standard therapy + roncoleukine 250 000 U/ml twice subcutaneously, every other day). II C – 17 adolescent girls with sub-acute (standard therapy). III group 42 patients with acute nonspecific vulvovaginitis. (standard therapy + roncoleukine 250 000 U/ml twice subcutaneously, every other day). Standard therapy of 7-10 days included [1,2]: Efficacy of the drug was assessed by patient complaints, inspection, and data of microbiological studies of vaginal discharge, immune state, cytokine status, and local phagocytic system on the 7th and 14th days of treatment.

Use of Human Immunoglobulins in Secondary Immunodeficiencies Associated with Hematological Malignancy in Real-Life Practice: Which Patients, Which Treatment?

IntroductionPatients with hematologic malignancies suffer of frequent, severe, and potentially life-threatening infections. Secondary immune deficiency (SID) could be due to the disease and/or to its treatment (immunosuppressants, immunomodulators, monoclonal anti-CD20 antibodies, corticosteroids for auto-immune cytopenia). Polyvalent immunoglobulins (Ig) prevent infections by restoring serum Ig level. Ig may be administered intravenously (IVIG) or subcutaneously (SCIG), in hospital setting or at home with same clinical benefit but various constraints. According to the recommendations, it is legitimate to propose Ig replacement therapy for these patients if the residual Ig rate is less than 5 g/L and/or several infectious accidents occurred. These recommendations are old and based on scarce data (1980’s and 1990’s studies), meantime, new therapies and clinical protocols have been developed to treat hematologic malignancies. Recent data regarding the clinical profile of patients receiving substitutive Ig in France are still scarce.ObjectiveThe EPICURE study aims to describe the clinical profile of patients with hematologic malignancies and SID who start a substitutive treatment with Ig. Secondary objectives are to describe the modalities of treatment with Ig (route, place for administration and dosing) and physicians expectation to this treatment.Patients and methodsStarting in 2011, EPICURE is an observational, prospective, longitudinal study involving 40 French centers. All adult SID patients with hematologic malignancies, receiving substitutive Ig may enter the study. To date, 240 patients have been included. We report the baseline data of the first 130 patients monitored.ResultsThe analysis focused on 130 patients (88 men, 42 women), aged 67 ± 12 years, with myeloma (N=27), chronic lymphocytic leukemia (N=47), non-Hodgkin B lymphoma either aggressive (N=19) or indolent (N=21) or other hematologic malignancies (N=21). Ten patients (7.7%) presented also autoimmune cytopenia (AIC). 50 patients (38.5%) were receiving antineoplastic chemotherapy (N=47) and/or immunosuppressants (N=8). 34 patients (26.2 %) have received a bone marrow transplant. Serum IgG level was < 5g/L in 67.4% of patients who had no monoclonal peak. Auto-immune disease (apart from AIC) (N=4), renal failure (N=6) and diabetes (N=13) potentially increased the risk of infection. 119 patients (91.5%) had a history of infection within the last 12 months for a total of 236 infectious episodes. 66 (28.0%) of these episodes have been severe (OMS grading ≥ 3), 77 (32.6%) have led to hospitalization for a total number of 972 days, 136 (57.6%) have required oral antibiotics and 59 (25.0%) have required intravenous antibiotics. Replacement therapy with Ig was started as IVIG in 62 patients (47.7%) and as SCIG in 68 patients (52.3%). Treatment with Ig was started in hospital setting for almost all patients (IVIG 100%, SCIG 95.6%) and was planned to be pursued at home for 1.6% of patients with IVIG but 98.5% of patients with SCIG. Physicians were expecting to avoid further infections, to improve quality of life and to decrease hospitalization rate. Mean dosing was 436±257 mg/kg/month in line with current recommendations.ConclusionPatients with SID associated with hematologic malignancies who start a replacement therapy with Ig were at high risk of severe infections and most of them had a low serum level of Ig. Ig replacement therapy was started subcutaneously in half of patients for a further planned administration at home. The other half of patients received IVIG for a further planned administration in hospital setting. Longitudinal monitoring will describe physician’s satisfaction regarding replacement therapy, evaluate infection incidence rate over the treatment period and define therapeutic profiles for a better care of these patients. DisclosuresNo relevant conflicts of interest to declare.

STATE OF IMMUNE SYSTEM IN PATIENTS WITH PRIMARY HEADACHES

High incidence of accompanying somatic diseases has been revealed in patients with primary headache syndromes, while clinical manifestations of immune disorders being quite prevalent among them. The most common immune pathology in the studied patients were secondary immune deficiency and allergic diseases. Significant differences in the rates of chronic inflammatory and allergic diseases in patients with episodic and chronic primary headaches allow of considering these conditions as a factor unfavorably affecting clinical course of cephalalgias. The results of laboratory examinations in the studied patients showed presence of immune deficiency features, with changing ratio of immune subpopulations, altered functional activity of neutrophils, decreased IgG levels, and imbalance in cytokine system.

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Introduction: Chylous effusions are a frequent complication after cardiac surgery in children and result in prolonged hospital stay and increase in other associated morbidities such as secondary immune deficiency and nutritional deficiencies. We sought to calculate the incidence and predictors of chylous effusion in children undergoing cardiac surgery at our center. Methods: We reviewed our hospital databases to identify cases with confirmed or suspected chylous effusions after undergoing surgery from January 1, 2009 to December 31st, 2011. Patients with documented chylous effusions in the medical record or those who were maintained on low-fat enteral formula were included as cases. Information on demographics, cardiac diagnosis, intra-operative course, and post-operative outcomes such as length of stay, days of chest tube retention, and infectious complications were collected. Results: During the study period, chylous effusions developed in 88 patients out of 995 who underwent cardiac surgery- an incidence of 9%. Chylous effusions occurred in younger patients (median age 4 days [0.0, 143.0 days- 25th, 75th percentile]) vs. median age of 434days [(59.0, 2697 days] in those with no chylous effusions {p<0.001}. Patients with chylous effusions had more complex cardiac lesions (highest Aristotle Score of 9 [7.0, 10.0] vs. 6.5 [6.0, 8.0]) {[p<0.001} and had longer cardiopulmonary bypass time (71 minutes [0.0, 124.0] vs. 149 minute [75.5, 235.0] {p<0.001}. Patients with chylous effusions had longer length of hospital stay (9.0 days [5.0, 24.8] vs. 64.5 days [30.8, 102.2 days] {p<0.001} and a higher incidence of positive blood, urine, respiratory and wound cultures (p<0.001 for each). A multivariable model shows age and highest Aristotle score to be predictive of development of chylous effusions. Conclusions: There is a significant incidence of chylous effusions in children undergoing cardiac surgery. These effusions are most likely to occur in young patients with more complex cardiac lesions. The occurrence of chylous effusions is associated with a significant increase in hospital stay and infectious complications.

Clinical use of polyvalent immunoglobulins.

Intravenous immunoglobulins (IVIG) and subcutaneous (SCIG) are used in treatment of a broad spectrum of diseases. Prepared from the collective plasma of several thousand people, therapeutic immunoglobulin consists mostly of human polyspecific IgG1–4. IgG replacement is the standard therapy for primary antibody deficiencies (PAD) aiming to replace the missing antibodies and thereby to prevent recurrent infections. Replacement therapy generally involves the use of 400–600 mg/kg administered every 3 or 4 weeks5–6. Debate continues regarding the exact timing and the optimal prophylaxis regimen, knowing that the system of care is itself an important determinant of patient outcomes7–8. The use of immunoglobulins as an immunomodulating therapy ranges from transplantation and treatment of autoimmune-haematological diseases to treatment of various neuroimmunological clinical entities9–10. Immunomodulating generally involves the use of 2 g/kg administered over either 2 or 5 consecutive days. US FDA approved IVIGs for the treatment of Primary Immune Deficiencies (PID), immune thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation in patients aged over 20 years, chronic B-cell lymphocytic leukaemia, and paediatric AIDS (Table I). Table I FDA approved indications for the therapeutical usage of polyvalent human immunoglobulins. Similarly, in Italy, the indications for IVIGs treatment include Primary Immune Deficiencies, immune thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation in patients aged over 20 years, chronic B-cell lymphocytic leukaemia and myeloma, paediatric AIDS and Guillain-Barre syndrome, and a new recently introduced indication (Table II). Table II Italian approved indications for the therapeutical usage of polyvalent human immunoglobulins. In addition to its use in primary and secondary immune deficiencies, many other clinical conditions might benefit from IVIGs therapy, all requiring documentation of contraindications to or a lack of response to conventional therapies according to US FDA (Table III). Some of these other conditions are extremely rare, making randomised controlled investigations difficult. Randomised clinical trials are warranted to support the evidence-based use of IVIg, and to identify the ideal administration protocols to maximise the benefits of what is a limited resource, knowing that many health care delivery systems are subjected to economic pressures and that individualised medicine and personalised health research presents methodological challenges11. Table III Clinical conditions that might benefit from immunoglobulin treatment according to Food and Drugs Administration additional approved indications with criteria. In this review we first discussed the issue of substitution treatment in primary antibody deficiencies, the choice of the immunoglobulin dosages, timing and the impact of therapy in survival. Then we discussed the immunoglobulin anti-inflammatory and immuno-modulating results in the treatment of immune-mediated demyelinating diseases, of rheumatological diseases (vasculitis and autoimmune connective tissue diseases), of haematological diseases (autoimmune cytopenias), of dermatological conditions (pemphigus and pemphigoid) and their usage in transplantation. Intentionally we did not address the issue of the off-label immunoglobulin treatments, despite their frequent usage carried on the basis of single case reports or uncontrolled studies.

CLINICAL AND LABORATORY FEATURES OF HHV-6 INFECTION IN IMMUNOCOMPROMISED CHILDREN FOLLOWED UP AT THE CHILDREN’S POLYCLINIC

In a cohort of 100 immunocompromised children aged 3 months to 12 years in continuous screening of saliva and urine with a qualitative polymerase chain reaction (PCR) assay DNA herpes virus 4, 5, 6, type (CMV, EBV, HHV-6) were verified in 76% of cases. DNA herpes virus type 6 was detected significantly more often (56%). On the material of the primary medical documentation and data of clinical and laboratory examination in conditions of a children's polyclinic there was performed the analysis of clinical and epidemiological risk factors for intrauterine infection (IUI), and clinical and laboratory markers of secondary immune deficiency (SID). It was made a suggestion about predominant vertical transmission of HHV-6 during the antenatal period. Based on 100 percent of detection of opportunistic herpes viral DNA in children aged 1-3 years the tactics of "antigenic sparing" in young children with SID was justified. To optimize the diagnostic measures in respect of immunocompromised children in conditions of a children's polyclinic the performance of a comprehensive screening PCR testing for HSV infections, including HHV-6, as well as immunological and bacteriological control is proposed.

Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury

Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency of AD increases, there is a corresponding increase in splenic leucopenia and immune suppression. Experimental activation of spinal sympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function.

Management of secondary immune deficiencies

Management of secondary immune deficiencies

Effect of malnutrition on the expression of cytokines involved in Th1 cell differentiation.

Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

Partial Exchange Transfusion for Hyperviscosity and Necrotizing Enterocolitis after Complication of Intravenous Immunoglobulin in a Late Preterm Infant: Case Report and Review of the Literature

Thrombocytopenia is not rare haematologic finding in the sick newborn infants, it occurs frequently in patients who were admitted to newborn intensive care units. Use of intravenous immunoglobulin (IVIG) in newborn infants has brought some amelioration to primary and secondary immune deficiencies, haemolytic disease of newborn, autoimmune thrombocytopenias and sepsis. There have been reports of thrombotic events in especially in adults and children after usage of high dose IVIG. However some unexpected adverse effects started to be reported by the increasing usage of IVIG. In this case we described a late preterm infant with necrotizing enterocolitis after IVIG treatment of neonatal isoimmune thrombocytopenia. After IVIG treatment, necrotizing enterocolitis began to occur and high blood viscosity was detected. We performed partially exchange transfusion. Thrombocyte numbers did not increase but significant improvement of clinical status occurred.

1014 – Clinical-immunological criteria of prognosis of protracted course of adjustment disorders

Various adverse factors and stressful situations result on one side in imbalance of immune system and weakening of mechanisms of immune protection, in formation of secondary immune deficiency and somatic pathology, on another - in stabilization of mental functions of the organism and adjustment disorder. Material and methods We have conducted clinical-immunological examination of 90 patients with adjustment disorder (F 43.2). Results From positions of clinical-dynamic approach, adjustment disorders have been differentiated depending on stage of development of disease: neurotic reactions (breakdown of mental adaptation), neurotic states (clinical full-blown states with sufficiently persistent neurotic symptoms and completion of formation of leading syndrome) and protracted states (developments, characterizing transition of the disease into chronic course). Diagnosis of clinical manifestations of secondary immune deficiency has shown increase of incidence rate of allergic and autoimmune syndromes in persons with adjustment disorder with protracted states as compared with previous stages of development of the illness. At this stage, we have more frequently observed combination of several syndromes of immune deficiency. Comparative analysis of immune and hormonal statuses has revealed the most informative indices, which characterize stages of development of adjustment disorders, and namely: total number of T-lymphocytes (CD2+-phenotype), level of serum IgM, indices of spontaneous and stimulated variants of NBT-test, level of cortisol and free thyroxin (T4). Conclusions Totality of alterations of revealed immunobiological indices is typical for every stage of disease that alongside with clinical signs of immune deficiency allows considering of them as an additional criterion in differential diagnostics of adjustment disorders.

P173 Etiological Factors For Adult Bronchiectasis Identified By A Specialized Investigation Protocol

RationaleNumerous factors have been identified as contributing to the development of bronchiectasis although their relative prevalence remains poorly understood. The Cambridge Centre for Lung Infection (CCRI) at Papworth Hospital has...