Specific Immunological Changes Research Articles

Immunological Changes and Complement Proteins in Major Thalassemia Patients Proteins Post-Splenectomy

Background: Thalassemia is one of the most prevalent genetic disorders worldwide, with infections being a leading cause of mortality due to compromised immune function. Specific Background: Prior studies suggest that major thalassemia patients are highly susceptible to microbial infections, possibly due to altered immunological profiles, particularly immunoglobulin (IgG, IgM) and complement (C3, C4) levels. Knowledge Gap: However, the specific immunological changes pre- and post-splenectomy in these patients remain underexplored. Aims: This study aims to assess the levels of immunoglobulins (IgG and IgM) and complement proteins (C3 and C4) in major thalassemia patients both before and after splenectomy compared to healthy controls. Results: Our analysis of 50 thalassemia patients (34 males, 16 females) and 30 healthy individuals revealed that thalassemia patients exhibited significantly lower levels of C3 and C4 (88.52±24.49, 21.20±6.66) compared to healthy controls (123.50±19.04, 32.87±9.77). IgG and IgM were elevated in patients (1288.12±467.87, 153.46±51.29) compared to controls (1129.93±295.96, 148.67±50.17). Post-splenectomy, patients showed a significant decline in IgG (1001.56±154.14) and IgM (110.08±25.83) levels, along with further decreases in C3 (83.28±24.13) and C4 (17.48±4.86). Novelty: This study provides novel evidence of the immunological shifts in thalassemia patients post-splenectomy, demonstrating significant reductions in both immunoglobulins and complement proteins, thereby elevating the risk of infection. Implications: These findings highlight the spleen's crucial role in maintaining immune competence and suggest that splenectomy in thalassemia patients requires careful post-operative immune monitoring to mitigate infection risks. Highlights: Splenectomy lowers IgG, IgM, C3, and C4 levels in thalassemia patients. Post-splenectomy patients face higher infection risk due to immune weakening. Highlights spleen's crucial role in immune defense for thalassemia patients. Keywords: Thalassemia, Splenectomy, Immunoglobulins, Complement Proteins, Immune Competence

COVID-19 Vaccination in Pregnancy: Pilot Study of Plasma MicroRNAs Associated with Inflammatory Cytokines after COVID-19 mRNA Vaccination.

The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

Pre-Implant Immune Status is Associated with Infection Risk After Left Ventricular Assist Device Implantation.

Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients. Fifty-four consecutive LVAD patients were included in this study. According to their infectious history in the first 3 months after LVAD implantation, these patients were grouped into an infection (n=23) and an infection-free group (n=31). Pre-LVAD blood samples were obtained for flow cytometric analysis of immunological parameters including B cells, subsets of T, dendritic and natural killer cells. Patient-specific, clinical and laboratory data were recorded. Blood count analysis prior to LVAD implantation showed comparable counts of erythrocytes (p=0.19), platelets (p=0.33) and leukocytes (p=0.50) between patients with infection and infection-free patients in the post-implant period. Patients with infection in the first 3 months after LVAD implantation had lower concentrations of lymphocytes (p=0.02). Forty percent of the patients with infection showed more often pre-LVAD neutrophil-to-lymphocyte ratios (NLR) >7 than patients without infection in the first 3 months after LVAD implantation (14%, p=0.05). Patients with infection already had lower percentages of CD3+ T cells (p=0.03), CD19+ B cells (p<0.01), BDCA2+ pDCs (p=0.03) and BDCA4+ plasmacytoid DCs (pDCs) (p=0.05) prior to LVAD implantation than infection-free patients. Our results demonstrated that patients with infection in the early post-implant period showed lower concentrations of lymphocytes, especially of CD3+ T cells and CD19+ B cells, decreased percentages of BDCA2+ and BDCA4+ pDCs, and had more often NLRs >7 indicating moderate-to-severe inflammation. Thus, we identified specific immunological changes pre-LVAD that could help to identify patients at risk for infection in the early post-implant period.

Вплив тютюнопаління на імунну відповідь та сприйнятливість жінок до інфекцій, що передаються статевим шляхом

The study highlights the importance of understanding the impact of cigarette smoking on the immune system, especially in women. It sets the context for the study by discussing the increasing concern about how lifestyle factors like smoking can affect susceptibility to infections, particularly STIs. Purpose - to explore how cigarette smoking affects the immune response in women and to investigate whether smoking increases the risk of contracting STIs. It seeks to identify specific immunological changes caused by smoking that could explain increased susceptibility to infections. Materials and methods. The methodology involves a comprehensive analysis of saliva samples from 160 women. This group includes both smokers and non-smokers, with some having chronic inflammatory diseases due to STIs. The study measures levels of immunoglobulins and lysozyme-peptide in the saliva to assess changes in the immune response. The results demonstrate significant alterations in immunoglobulin levels and lysozyme-peptide in the saliva of women who smoke, especially those with chronic inflammatory diseases caused by STIs. These findings indicate that smoking can modify local immunity and exacerbate the immune response to inflammatory processes associated with STIs. Conclusions. The study concludes that cigarette smoking has a critical impact on women's reproductive health by altering their immune response and increasing their susceptibility to STIs. It underscores the need for greater attention to smoking as a major public health issue, emphasizing its role in women's health and the importance of incorporating smoking cessation strategies in disease prevention programs. The study protocol was approved by the Local ethics committees of the institutions mentioned in the paper. An informed parental consent was obtained for the study in women. No conflict of interests was declared by the authors.

Specific Clinical and Immunological Changes Following Mesenchymal Stem Cell Transplantation in COVID-19-induced Acute Respiratory Distress Syndrome Patients: A Phase-I Clinical Trial.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1× cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells. These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

Local Targeting of NAD+ Salvage Pathway Alters the Immune Tumor Microenvironment and Enhances Checkpoint Immunotherapy in Glioblastoma.

The aggressive primary brain tumor glioblastoma (GBM) is characterized by aberrant metabolism that fuels its malignant phenotype. Diverse genetic subtypes of malignant glioma are sensitive to selective inhibition of the NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). However, the potential impact of NAD+ depletion on the brain tumor microenvironment has not been elaborated. In addition, systemic toxicity of NAMPT inhibition remains a significant concern. Here we show that microparticle-mediated intratumoral delivery of NAMPT inhibitor GMX1778 induces specific immunologic changes in the tumor microenvironment of murine GBM, characterized by upregulation of immune checkpoint PD-L1, recruitment of CD3+, CD4+, and CD8+ T cells, and reduction of M2-polarized immunosuppressive macrophages. NAD+ depletion and autophagy induced by NAMPT inhibitors mediated the upregulation of PD-L1 transcripts and cell surface protein levels in GBM cells. NAMPT inhibitor modulation of the tumor immune microenvironment was therefore combined with PD-1 checkpoint blockade in vivo, significantly increasing the survival of GBM-bearing animals. Thus, the therapeutic impacts of NAMPT inhibition extended beyond neoplastic cells, shaping surrounding immune effectors. Microparticle delivery and release of NAMPT inhibitor at the tumor site offers a safe and robust means to alter an immune tumor microenvironment that could potentiate checkpoint immunotherapy for glioblastoma. SIGNIFICANCE: Microparticle-mediated local inhibition of NAMPT modulates the tumor immune microenvironment and acts cooperatively with anti-PD-1 checkpoint blockade, offering a combination immunotherapy strategy for the treatment of GBM.

TAMI-30. LOCAL TARGETING OF NAD+ SALVAGE PATHWAY ALTERS THE IMMUNE TUMOR MICROENVIRONMENT AND ENHANCES CHECKPOINT IMMUNOTHERAPY IN GLIOBLASTOMA

Abstract The aggressive primary brain tumor glioblastoma (GBM) is characterized by aberrant metabolism that fuels its malignant phenotype. Diverse genetic sub-types of malignant glioma are sensitive to selective inhibition of the NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). However, the potential impact of NAD+ depletion on the brain tumor microenvironment has not been elaborated. In addition, systemic toxicity of NAMPT inhibition remains a significant concern. Here, we show that microparticle-mediated intratumoral delivery of NAMPT inhibitor GMX1778 induces specific immunological changes in the tumor microenvironment of murine GBM, characterized by upregulation of immune checkpoint PD-L1, recruitment of CD3+, CD4+ and CD8+ T cells and reduction of M2-polarized immunosuppressive macrophages. NAD+ depletion and autophagy induced by NAMPT inhibitors mediated the upregulation of PD-L1 transcripts and cell surface protein levels in GBM cells. NAMPT inhibitor modulation of the tumor immune microenvironment was therefore combined with PD-1 checkpoint blockade in vivo, significantly increasing the survival of GBM bearing animals. Thus, the therapeutic impacts of NAMPT inhibition extended beyond neoplastic cells, shaping surrounding immune effectors. Microparticle delivery and release of NAMPT inhibitor at the tumor site offers a safe and robust means to alter an immune tumor microenvironment that could potentiate checkpoint immunotherapy for glioblastoma.

A prevalence study of vaginal candidiasis among pregnant women

Background: Pregnancy is associated with specific anatomical, physiological and immunological changes that can predispose to infection and also alter the response to the disease process. Infections in pregnancy demands prompt adequate and careful management. The disease process as well as the treatment protocol may have profound effects on the outcome of pregnancy. Pregnant women frequently develop vaginal discharge which can lead to complications during pregnancy like abortions, premature birth, low birth weight and other morbidities. Some of the infections may be serious and life threatening for the mother while others may seriously jeopardize the fetus or neonate leaving the mother asymptomatic. The aim and objective of this study was based on the present study was aimed to study the prevalence of vaginal candidiasis among pregnant patients who were visited in outdoor patient’s department of Prasutitantra and Streeroga.Methods: About 135 high vaginal swabs were collected from the women who carrying 2nd and 3rd trimester of pregnancy with symptoms of vaginal infection. These samples were tested under microscopic examination and culture on Mac Conkey agar, blood agar and Sabouraud dextrose agar respectively. Colonial morphology, wet/K.O.H. preparation, gram staining, germ tube test, were carried out for identification of the isolated organisms.Results: Out of 135 samples collected, 61 (45.18%) patients were shown positive fungal infection of candidial species. The age group showing the highest number of positive candidiasis was of 20 to 25 years. Multigravida (60%) were more commonly affected than primigravida (40%) and commonly seen in third trimester (67.41%).Conclusions: Vaginal Candidiasis was common in pregnant women with more common in young adults.

Management of Upapluta Yonivyapad (Vulvovaginitis) during Pregnancy - A Case Study

Pregnant women commonly develop increased vaginal discharge, which in many instances is not pathological. Pregnancy is associated with specific anatomical, physiological and immunological changes that can predispose to infection and also alter the response to the disease process. Infections in pregnancy demands prompt adequate and careful management. Vulvovaginitis during pregnancy may be considered under the umbrella of Upapluta Yonivyapad. Pregnant women are more prone to vulvovaginitis which is a great challenge for obstetricians today. In Ayurveda, Upapluta Yonivyapad described by Acharaya Charaka, Sharangadhara and both Vagbhata can be compared to vulvovaginitis during pregnancy. Here Panchawalkala Kwatha Prakshalna followed by Jatyadi Taila Pichu externally and Tab Leukol internally has been used to correct Garbhini Upapluta.

Executive control, ERP and pro-inflammatory activity in emotionally exhausted middle-aged employees. Comparison between subclinical burnout and mild to moderate depression

Burnout is a syndrome occurring mainly in individuals with long-term stressful work. The main complaints are emotional exhaustion and reduced performance. Burnout also largely overlaps with depression. Both are characterized by increased incidence of infections due to dysregulation of the immune system, overexpression of pro-inflammatory cytokines and cognitive deficits, particularly related to executive functions. To distinguish between burnout and depression already at the pre-clinical stage, the present double-blinded study compared immunological and cognitive parameters in seventy-six employees from emotionally demanding occupations who were post-hoc subdivided into two groups scoring low (EE−) and high (EE+) in emotional exhaustion and low (DE−) and high (DE+) in depression. Immunological parameters were measured from blood samples. Executive functions were studied by analyzing event-related brain potentials (ERPs) and performance during a task switching paradigm. Psychosocial job parameters were measured with standardized questionnaires.Burnout and mild to moderate depression largely overlapped. However, several subjects showed burnout without depressive symptoms. Higher levels of the pro-inflammatory cytokines IL-6 and IL-12 were correlated with burnout severity and depressive symptoms in male individuals. In the switch task a trend for lower performance in the EE+ vs. EE− group and no difference between DE+ and DE− groups were found. In the ERPs, however, differences were observed which distinguished between subclinical burnout and depression: the terminal contingent negative variation (CNV), indicating preparatory activity and the P3b, related to allocation of cognitive resources were generally reduced in EE+ vs. EE−, whereas no differences were found in the DE+ vs. DE− groups. The frontal P3a was selectively reduced in switch trials in the EE+ vs. EE− group and showed only a trend in DE+ vs. DE−, indicating impairment of executive control in subclinical burnout. Taken together, the results unveil specific immunological changes and declines in brain functions in employees with subclinical burnout that are not apparent in persons with moderate depression. Hence, the combination of immunological, behavioral and ERP methods renders a promising method for distinguishing both syndromes and for improving an early diagnosis of burnout before a clinical stage is reached.

Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis.

Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4(+) central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4(+) transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4(+) TCM cells, (ii) increased levels of CD4(+) T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR(+) CD8(+) T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4(+) TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV-infected sooty mangabeys, a natural host for the infection, with a potent antiretroviral therapy (ART) regimen for periods ranging from 2 to 12 months and monitored in detail how suppression of virus replication affected the main virological and immunological features of this nonpathogenic infection. The observed findings provide novel information on both the pathogenesis of residual immunological disease under ART during pathogenic infection and the mechanisms involved in virus persistence during primate lentiviral infections.

Enthesopathies and enthesitis. Part 1. Etiopathogenesis.

The pathologies of tendon and ligament attachments are called enthesopathies. One of its types is enthesitis which is a characteristic sign of peripheral spondyloarthropathy. Clinical diagnosis of enthesitis is based on rather non-specific clinical signs and results of laboratory tests. Imaging examinations are highly promising. Numerous publications prove that enthesitis can be differentiated from other enthesopathic processes in an ultrasound examination or magnetic resonance imaging. However, some reports indicate the lack of histological criteria, specific immunological changes and features in imaging examinations that would allow the clinical diagnosis of enthesitis to be confirmed. The first part of the publication presents theories on the etiopathogenesis of enthesopathies: inflammatory, mechanical, autoimmune, genetic and associated with the synovio-entheseal complex, as well as theories on the formation of enthesophytes: inflammatory, molecular and mechanical. The second part of the paper is a review of the state-of-the-art on the ability of imaging examinations to diagnose enthesitis. It indicates that none of the criteria of inflammation used in imaging medicine is specific for this pathology. As enthesitis may be the only symptom of early spondyloarthropathy (particularly in patients with absent HLA-B27 receptor), the lack of its unambiguous picture in ultrasound and magnetic resonance scans prompts the search for other signs characteristic of this disease and more specific markers in imaging in order to establish diagnosis as early as possible.

The Effect of Fingolimod on Peripheral Blood Mononuclear Cell Phenotypes: A Prospective Study (P02.122)

Objective: To report changes in peripheral blood lymphocyte subpopulations in patients with relapsing-remitting multiple sclerosis (RRMS) treated with fingolimod prospectively over 6 months and to explore potential surrogate markers that may be associated with a clinical response to treatment. Background Fingolimod is a recently approved drug for treating RRMS inhibiting the sphingosine-1-phosphate-dependent lymphocyte egress from secondary lymphoid tissues resulting in reversible lymphopenia. Specific immunological changes in the peripheral venous blood have only been explored cursory in small patient numbers. Design/Methods: This is a prospective, multi-center, single-arm, open-label study in 445 RRMS patients receiving 0.5 mg fingolimod. At predefined time points (baseline, 1 month, 4 months, as well as 6 months after treatment initiation) blood samples were obtained. Leukocytes were analyzed by flow cytometry for the expression of various surface markers (CD3, CD4, CD8, CD16, CD19, CD34, CD45RA, CD56, CCR7), whereas serum samples were analyzed for the presence of various cytokines, such as for Th1, Th2 and Th17 responses. Results: The analysis of the first 100 patients revealed that the number of CD45 positive cells decreased and maintained at low levels for the follow-up. Numbers of CD4+, CD8+, and CD19+ cells were lowered. The change in the CD4+/CD8+ ratio was determined by an intended reduction of CD4+ T cells and a slight reduction of CD8+ T cells. CD4+ cells however, were never found to be depleted. For the majority of the cytokines tested so far, no significant alterations were found. The study is still ongoing and data for the majority of the patients will be available. Conclusions: Fingolimod induces a robust effect predominantly on CD4+ T cells, an effect maintained over time. Biomarkers predicting clinical efficacy and/or safety signals have not been identified yet and require further prospective studies. Supported by: Novartis Pharma GmbH, Nuernberg, Germany. Disclosure: Dr. Dehmel has nothing to disclose. Dr. Opgenoorth has nothing to disclose. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Genzyme Corporation, Merck Serono, Novartis, Sanofi-Aventis and Teva as a speaker and/or consultant. Dr. Diaz-Lorente has received personal compensation for activities with Novartis Pharmaceuticals as an employee. Dr. Kieseier has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novartis, Roche Diagnostics, Sanofi-Aventis Pharmaceuticals, and TEVA Neurosciences as speaker. Dr. Kieseier has received research support from Bayer Pharmaceuticals, Biogen Idec, Merck Serono and Teva Neurosciences.

Microfluidics for T‐ Lymphocyte Cell Separation and Inflammation Monitoring in Burn Patients

Severe burns result in T lymphocyte specific immunologic changes. In addition to decreased levels of circulating lymphocytes, changes in cytokine secretion and receptor expression also take place. Our finer understanding of the inflammatory response has led to the development of immune-targeted therapeutics, requiring specialized gene-expression monitoring. The emerging field of bio-micro-electromechanical systems can be used to isolate highly pure T lymphocytes in a clinically relevant and timely manner for downstream genomic analysis. Blood samples from healthy volunteers and burn-injured patients were introduced into microfluidic devices developed in our laboratory. Utilizing cell-affinity chromatography for positive selection of T lymphocytes, the devices served as a platform for RNA extraction and downstream cytokine analysis via quantitative real-time polymerase chain reaction (PCR). From a 0.5-mL whole blood sample, the microfluidic devices captured highly pure T lymphocytes from healthy volunteers and burn-injured patients. Cell capture was of sufficient quantity, and extracted RNA was of sufficient quality, for evaluating the gene expression of cytokines: interferon-gamma, interleukin-2, interleukin-4, and interleukin-10. Microfluidics is a useful tool in processing blood from burn-injured patients. Though in its very early stages of development, cell-specific information obtained by this platform/technology will likely be an important component of near-patient molecular diagnostics and personalized medicine.

Detection of Staphylococcus Aureus in Nasal Tissue with Peptide Nucleic Acid–Fluorescence in Situ Hybridization

Staphylococcus aureus (SA) in the nose can be a simple colonizer but also may create an intramucosal reservoir causing recurrent infections or can be a specific immune modulator through superantigenic mechanisms. Because the colonization rate of SA is high, but immunologic reactions causing chronic disease are less frequent, the purpose of this study was to identify the presence of intramucosal SA in healthy subjects and in patients with chronic rhinosinusitis (CRS) and to eventually relate those to the specific immunologic changes due to SA enterotoxins. Nasal tissue was collected in 40 subjects (9 controls, 21 CRS patients with [CRSwNP], and 10 CRS patients without nasal polyps [CRSsNP]). Tissues were homogenized, and mediators and specific IgE-antibodies against SA enterotoxins (SAE-IgE) were measured using the UniCAP system. The tissue was analyzed for the presence of SA by the peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) technique (AdvanDx), and a semiquantitative scoring system was applied. Mann-Whitney exact test was used for statistical analysis. SA in the mucosal tissue was detected in a higher quantity among CRSwNP subjects with aspirin exacerbated respiratory disease (AERD) versus controls and CRSsNP (p=0.03). Among CRSwNP patients, Th2 markers (eosinophil cationic protein, p=0.006, and total IgE, p=0.004) were increased related to the SAE-IgE status but not related to the presence of SA in the tissue. This study describes the detection of SA within nasal tissue using the PNA-FISH technique. The presence of SA in the submucosa did not correlate with the amplification of the Th2-related inflammation typically found in CRSwNP patients, but this reaction is dependent on the formation of SAE-IgE within mucosal tissue. We also show, for the first time, that submucosal SA is a prevalent finding in CRSwNP patients with AERD.

Immunotherapy with Wasp Venom is Accompanied by Wide-ranging Immune Responses That Need Further Exploration

Immunotherapy with wasp allergen leads to a variety of specific immunological changes. It is unknown, however, whether unspecific effects also occur, and which parameter shifts might indicate treatment success. Therefore, data of patients who had completed immunotherapy with wasp venom were analysed retrospectively for a change in the following parameters after therapy: threshold of skin tests with wasp venom, total and specific serum IgE, specific serum IgG and IgG4, and binding of IgE and IgG4 to major wasp venom allergens. Reactions to field stings were explored. A significant increase in the skin test threshold and a significant decrease in total serum IgE, specific serum IgE and major wasp allergens binding IgE were found. Concentrations of specific serum IgG and IgG4 increased. Patients with corresponding changes in at least three specific parameters did not report severe reactions to verified field stings after therapy. The marked decrease in total serum IgE indicates that wasp immunotherapy has wide-ranging immunological effects, and it appears reasonable to check combinations of several parameters for treatment control.

Lupus erythematosus associated with erythema multiforme: Rowell's syndrome

About 45 years ago, the association of lupus erythematosus with erythema multiforme and specific immunological laboratory changes was described for the first time. Since then, several patients with similar constellations of clinical symptoms and laboratory parameters have been reported. Today, this disease is known as Rowell's syndrome. However, the fact that not all patients described previously fit all clinical and immunological characteristics that had been originally reported raised the question if Rowell's syndrome really is an own entity or if the simultaneous occurrence of these clinical and immunological signs is rather incidental. Here, we describe a patient fulfilling most of the criteria of Rowell's syndrome and discuss what is currently known about this rare condition.

Idiopathic pericarditis in dogs: no evidence for an immune‐mediated aetiology

To ascertain whether specific immunological changes are associated with canine pericardial effusion due to idiopathic pericarditis. In this prospective study, serum antinuclear antibody and serum and pericardial fluid immunoglobulin (Ig) G, Ig M and Ig A concentrations were measured in dogs with pericardial effusion due to idiopathic pericarditis or pericardial neoplasia. The secretory index relative to albumin concentration was calculated in order to distinguish between Ig actively secreted into the pericardial fluid and that derived from the blood accumulating within the pericardial sac. Statistical analysis was performed comparing the results obtained between the two groups of dogs. Only three dogs were antinuclear antibody positive; two of these dogs had idiopathic pericarditis and one had neoplasia. Mean serum Ig M and Ig A concentrations were lower than the reference values in both groups, and the secretory indices for Ig M and Ig A were greater than 1.0. However, there was no significant difference with respect to any Ig measurement between the two groups of dogs (P>0.1). The results of the present study do not support the hypothesis that canine idiopathic pericarditis has a significant 'immune-mediated' aetiology or immunological features that distinguish it from the pericardial changes associated with local neoplastic disease.

Of mothers and malaria

Malaria in Pregnancy: Deadly Parasite, Susceptible Hostedited by P.E. Duffy and M. Fried, Taylor & Francis, 2001. £45.00 (hbk) (245 pages) ISBN 0 415 272181Serving as a sobering reminder of the burden of malaria during pregnancy, recent estimates in Africa have attributed up to 300 000 infant deaths to the infection each year, with ∼25 million pregnancies potentially at risk annually. Given the enormity of the problem, it is heartening to see the publication of a new book devoted to maternal malaria.An examination of the epidemiology of malaria in pregnancy, by B. Brabin and S. Rogerson, clearly defines the nature and extent of the disease. Infection results in substantial anaemia, contributing to the high maternal death rate common to tropical countries, and complications are influenced by the extent of prior exposure. Newborns of infected mothers are at high risk of dying in their first year due to intra-uterine growth retardation and premature delivery, leading to low-birth-weight babies and other complications. Plasmodium falciparum accounts for the bulk of disease and is the predominant species in Africa, but it is now increasingly recognized that Plasmodium vivax also has a substantial impact on maternal and infant health.There are two particularly intriguing features of malaria in pregnancy. First, pregnant women are significantly more susceptible than non-pregnant adults to malaria and its complications, despite pre-existing immunity. This appears, predominantly, to be a result of a reduced ability to clear established infection rather than higher infection rates, and is reflected in more frequent treatment failures and relapses. Careful studies are beginning to detail the nature of specific immunological changes during pregnancy that account for this and the immune responses that occur following exposure, reviewed by P. Duffy, L. Guilbert, M. Abbasi and T. Mosmann. Second, in P. falciparum infection, large numbers of parasitized erythrocytes typically accumulate in the maternal blood spaces of the placenta, associated with inflammatory responses characterized by a monocyte and/or macrophage infiltrate. Recent reports suggest that specific parasite variants infect the placenta, and the adhesive events mediating this process have been identified, involving glycosaminoglycans and immunoglobulins. This is an exciting and rapidly developing field that has stimulated great interest in the notion of vaccine development specifically targeting variants that adhere in the placenta and is given particular attention in the chapters by Duffy and M. Fried.Whereas uncovering mechanisms of infection and immunity could eventually lead to lasting interventions, such as vaccination, a growing understanding of the use and benefits of chemotherapy and chemoprophylaxis during pregnancy has emphasized the urgent need for improved control of maternal malaria in risk populations, highlighted by F. Nosten, R. McGready, T. Mutabingwa and L. Villegas. It is now generally accepted that intermittent chemoprophylaxis is an effective intervention in many endemic areas and should be widely implemented. Furthermore, treatment requires special consideration given potential fetal toxicity of antimalarials, particularly with the use of new agents in the setting of drug resistance, and safe and effective regimens are being developed in response to these needs.Sections on the history of malaria in pregnancy research (Duffy and R. Desowitz), providing extensive reference to old texts that modern researchers would otherwise have difficulty accessing, and on insights from animal studies (Desowitz) which have received limited attention in recent times, are other welcome inclusions.The book is an excellent summary of current knowledge and a valuable resource for those working in malaria and, more broadly, for researchers in parasitology and tropical medicine. The contributing authors have generally left few stones unturned in providing broad and stimulating reviews of key issues. A strength of the book is that many of the authors either work or have worked in malaria-endemic countries and therefore bring practical knowledge with their scientific expertise.

Evidence That Sunscreens Prevent UV Radiation-Induced Immunosuppression in Humans

IT has been known for over two decades that induction of malignant skin tumors in rodents by midrange UV radiation (UVB radiation, 280 to 320 nm) involves not only an oncogenic event within the epidermis but also specific immunologic changes that serve to prevent or inhibit a vigorous immune response against the incipient tumor by the host immune system. 1 Ultraviolet B—induced tumors in mice are highly immunogenic and fail to grow when transplanted to syngeneic recipients. 2-4 Indeed, the transplanted tumors are destroyed and immunologic memory against the transplanted tumor can be detected. This observation led to a series of studies aimed at understanding why these immunogenic tumors grow in the primary host. UV RADIATION INDUCES SPECIFIC IMMUNOLOGIC CHANGES IN MICE Experiments performed in the 1970s by Kripke 2,3 and Roberts et al 4 demonstrated that prolonged and repetitive exposure to UVB radiation results not only in the appearance