Elevated Levels Of IgG Antibodies Research Articles

Autoantigen-selected B cells are bystanders in spontaneous T cell-driven experimental autoimmune hepatitis.

Autoreactive B cells are considered pathogenic drivers in many autoimmune diseases; however, it is not clear whether autoimmune B cells are invariably pathogenic or whether they can also arise as bystanders of T cell-driven autoimmune pathology. Here, we studied the B cell response in an autoantigen- and CD4+ T cell-driven model of autoimmune hepatitis (AIH), the Alb-iGP_Smarta mouse in which expression of a viral model antigen (GP) in hepatocytes and its recognition by GP-specific CD4+ T cells causes spontaneous AIH-like disease. T cell-driven AIH in Alb-iGP_Smarta mice was marked by autoantibodies and hepatic infiltration of plasma cells and B cells, particularly of isotype-switched memory B cells, indicating antigen-driven selection and activation. Immunosequencing of B cell receptor repertoires confirmed B cell expansion selectively in the liver, which was most likely driven by the hepatic GP model antigen, as indicated by branched networks of connected sequences and elevated levels of IgG antibodies to GP. However, intrahepatic B cells did not produce increased levels of cytokines and their depletion with anti-CD20 antibody did not alter the CD4+ T cell response in Alb-iGP_Smarta mice. Moreover, B cell depletion did not prevent spontaneous liver inflammation and AIH-like disease in Alb-iGP_Smarta mice. In conclusion, selection and isotype-switch of liver-infiltrating B cells was dependent on the presence of CD4+ T cells recognizing liver antigen. However, recognition of hepatic antigen by CD4+ T cells and CD4+ T cell-mediated hepatitis was not dependent on B cells. Thus, autoreactive B cells can be bystanders and need not be drivers of liver inflammation in AIH.

SERUM ANTIBODIES AGAINST GroEL AS AN ADDITIONAL RISK BIOMARKER OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY.

Thelevel of heat shock protein 60 (Hsp60) is elevated in tumor cells compared with normal prostate epithelium. Hsp60is involved in tumor growth, invasion, and metastasis and is considered as a biomarker for cancer diagnosis and prognosis. To study thelevel of antibodies against prokaryotic homolog of human Hsp60 (GroEL) in prostate cancer (PCa) patients as an additional risk marker for theprediction of biochemical recurrence after radical prostatectomy (RP). A total of 55patients with localized and locally advanced PCa, who had undergone RP between July 2013and May 2014were enrolled. Level of antibodies to GroEL and human Hsp60was determined by enzyme-linked immunosorbent assay before surgery. Serum samples of blood donors with low reactivity to GroEL and human Hsp60were used as controls. Therelationship between IgG antibodies against bacterial Hsp60and human Hsp60and clinicopathological features were analyzed. Thebiochemical recurrence (BCR) free survival rate was estimated by theKaplan - Meier method. Theunivariate and multivariate Cox regression models were used to evaluate therisk factors of BCR-free survival rate. There were significant differences in anti-GroEL IgG levels between control and PCa patients while no significant differences in anti-human Hsp60IgG levels between control and PCa patients were detected. During thefollow-up period, 40/55 (72.7%) patients developed BCR. Thetime from surgery to BCR was from 18to 72months. Elevated IgG antibodies against bacterial Hsp60in patients who had undergone RP were associated with early occurrence of biochemical relapse and lower 5-year BCR-free survival rate respectively (p < 0.001). Themultivariate analysis indicated that IgG to GroEL (hazard ratio = 2.465; 95% confidence interval: 1.311-4.634, p < 0.05) could be independent prognostic factor in thepatients who had developed BCR. Elevated levels of IgG antibodies against GroEL before surgery can predict early occurrence of BCR after RP and can serve as an additional independent risk biomarker of a BCR after RP.

Evidence of orthohantavirus and leptospira infections in small mammals in an endemic area of Gampaha district in Sri Lanka

BackgroundOrthohantaviruses and leptospira are emerging zoonotic pathogens of high public health significance. The epidemiology of orthohantavirus infections and leptospirosis is similar and presents related clinical pictures in humans. However, a paucity of data on actual reservoir hosts for orthohantaviruses and leptospira exists. Therefore, this study aimed at determining the occurrence of orthohantaviruses and leptospira in small mammals captured in an endemic region of Sri Lanka.MethodsRodents and shrews were morphologically and/or genetically identified using morphological keys and DNA barcoding techniques targeting the cytochrome oxidase b subunit gene (Cytb). Lung tissues and sera were subsequently analyzed for the presence of orthohantavirus RNA using qRT-PCR. Sera of rats were tested for IgG antibodies against orthohantaviruses and leptospira.ResultsForty-three (43) small mammals representing: Rattus (R.) rattus (black rat) or R. tanezumi (Asian rat), Suncus murinus (Asian house shrew), R. norvegicus (brown rat) and Mus musculus (house mouse) were investigated. No orthohantavirus RNA was detected from the lung tissue or serum samples of these animals. Elevated levels of IgG antibodies against Puumala orthohantavirus (PUUV) and/or Seoul orthohantavirus (SEOV) antigens were detected in sera of 28 (72%) out of the 39 rats analysed. Interestingly, 36 (92%) of the 39 rats also showed presence of anti leptospira-IgG antibodies in their serum, representing dual infection or dual exposure in 26/39 (66.7%) of examined rats.ConclusionsThis project targets important public health questions concerning the occupational risk of orthohantavirus infections and/or leptospirosis in an endemic region of Sri Lanka. Most rats (72%) in our study displayed antibodies reacting to orthohantavirus NP antigens, related to PUUV and/or SEOV. No correlation between the orthohantavirus and leptospira IgG antibody levels were noticed. Finally, a combination of both morphological and DNA barcoding approaches revealed that several species of rats may play a role in the maintenance and transmission of orthohantavirus and leptospira in Sri Lanka.

Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus.

Mitochondria are organelles that exhibit several bacterial features, such as a double-stranded genome with hypomethylated CpG islands, formylated proteins, and cardiolipin-containing membranes. In systemic lupus erythematosus (SLE), mitochondria and their inner components are released into the extracellular space, potentially eliciting a proinflammatory response from the immune system. While cardiolipin and mitochondrial DNA and RNA are confirmed targets of autoantibodies, other antigenic mitochondrial proteins in SLE remain to be identified. The present study was undertaken to characterize the protein repertoire recognized by antimitochondrial antibodies (AMAs) in patients with SLE. Using shotgun proteomic profiling, we identified 1,345 proteins, 431 of which were associated with the mitochondrial proteome. Immunoreactivities to several of these candidate proteins were assessed in serum samples from a local cohort (n = 30 healthy donors and 87 patients with SLE) using enzyme-linked immunosorbent assay, and further analyzed for associations with demographic and disease characteristics. We determined that IgG antibodies to the complement component C1q binding protein were significantly elevated in the patients with SLE (P= 0.049) and were also associated with lupus anticoagulant positivity (P= 0.049). Elevated levels of IgG antibodies against mitochondrial protein mitofusin 1 (MFN-1) were promising predictors of SLE diagnosis in our cohort (adjusted odds ratio 2.99 [95% confidence interval 1.39-6.43], P= 0.0044). Moreover, increased levels of anti-MFN-1 were associated with the presence of antiphospholipids (P= 0.011) and anti-double-stranded DNA (P= 0.0005). In this study, we characterized the mitochondrial repertoire targeted by AMAs in the setting of SLE. Our results indicate that autoantibodies can recognize secreted and/or surface proteins of mitochondrial origin. Profiling of the AMA repertoire in large prospective cohorts may improve our knowledge of mitochondrial biomarkers and their usefulness for patient stratification.

MULTIPLE TROMBOSIS IN CHILD WITH POST COVID-19 INFECTION

Introduction: SARS CoV-2 infection can cause acute, as well as chronic damage to the cardiovascular system. Blood vessel dysfunction and clot formation, as suggested by elevated D-dimer levels, are thought to play a significant role in morbidity, as well as in mortality in Covid-19 patients, leading to clots causing pulmonary embolisms and ischemic events within the brain1. Aim: To confirm the correlation between SARS CoV-2 infection and possibility for vascular complication, including thrombotic brain lesion. Materials: Detailed patient’s history, physical examination particularly noting the neurological status and locomotor skills, as well as blood analysis with hemostasis and d-dimers, serology for SARS CoV-2 IgG antibodies and PCR swab were all part of the diagnostic process for this patient. Methods: Computed tomography and brain MRI with angiography were main imaging tools used in the diagnostic process. Results: Thrombosis of the left middle cerebral artery was confirmed on brain MRI with angiography in a patient recovered from SARS CoV-2 infection, noted with high levels of IgG antibodies to the particular virus and elevated D-dimer levels, presenting with symptomatic right sided hemiparesis. Conclusion: Some of the patients recovered from SARS CoV 2 infection can develop ischemic stroke. This link is confirmed by elevated levels of IgG antibodies in patient’s serum against SARS CoV-2. This kind of vascular post viral complication can cause different kind of disability, presented with neurological impairment and coagulation disorders. The prognose is improving with anticoagulant and physical therapy started early.2 Keywords: Thrombosis, SARS Cov-2, Brain, Hemiparesis

English

BACKGROUND Coronavirus disease - 19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Anti-SARS-CoV-2 IgM and IgG antibodies can be detected in almost all patients of COVID-19. We sought to evaluate the antibody responses in COVID19 patients and also analyse their potential role in disease prognostication. METHODS All consecutive COVID-19 patients, between ages 20 - 65 years, encountered between April and July 2020 were included and compared to age-matched controls. Severity of the SARS-CoV-2 infection was categorized as none, mild and severe, based on the presence of symptoms, oxygen saturation and need for respiratory support. Serum levels of IgM and IgG antibody assays were obtained, using chemiluminescence immunoassay, after the 2nd week of presentation (range 14 - 60 days). Antibody titres above 10 AU/ml were taken as elevated. RESULTS Of 50 eligible patients, majority (40/50, 80 %) had mild symptoms and oxygen saturations above 94 %. Of the remainder, 10 % (5/50) had severe infection with need for either high flow nasal cannula oxygen or mechanical ventilation while the remainder (10 %; 5/50) were asymptomatic. IgM and IgG seroconversion were noted in almost all COVID-19 patients (46/50, 92 %) compared to healthy controls. While elevated IgG antibody levels were noted in 76 % (38/50), combined elevation of IgM and IgG antibodies is seen in 16 % (8/50) of patients. Seroconversion was markedly profound in patients with severe infection than those with mild infection. Also, greater seroconversion was noted after 21 days of testing compared to 14th day, especially for IgG. CONCLUSIONS Antibody seroconversion to SARS-CoV-2 occurred in majority of patients with COVID-19, with most salient increase in the IgG antibody levels. Antibody titres correlated directly to the disease severity, suggestive of the potential value of antibodies not only in diagnosis but also in prognostication. KEYWORDS COVID-19, Chemiluminescence Immunoassay, Invasive Mechanical Ventilation, High Flow Nasal Oxygen

Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response.

The RV144 HIV-1 vaccine trial results showed moderate reduction in viral infections among vaccinees as well as induction of antibody-dependent cellular cytotoxicity and vaccine-specific IgG and IgG3 responses directed at variable loop regions 1 and 2 of the HIV envelope protein. However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. One of the changes included in the HVTN 702 study was the addition of a late boost, aimed at augmenting peak immunity and durability. The companion vaccine trial RV305 was designed to permit the evaluation of the immunologic impact of late boosting with either the boosting protein antigen alone, the canarypox viral vector ALVAC alone, or a combination of both. Although previous data showed elevated levels of IgG antibodies in both boosting arms, regardless of ALVAC-HIV vector incorporation, the effect on shaping antibody effector function remains unclear. Thus, here we analyzed the antibody and functional profile induced by RV305 boosting regimens and found that although IgG1 levels increased in both arms that included protein boosting, IgG3 levels were reduced compared with the original RV144 vaccine strategy. Most functional responses increased upon protein boosting, regardless of the viral vector-priming agent incorporation. These data suggest that the addition of a late protein boost alone is sufficient to increase functionally potent vaccine-specific antibodies previously associated with reduced risk of infection with HIV.

Analysis of the effectiveness and long-term results of formation of adaptive immunity in the use of various medications and vaccination schemes against pneumococcal infection in patients with chronic obstructive pulmonary disease

To assess the long-term clinical results of vaccination with pneumococcal polysaccharide and conjugated polysaccharide vaccines in the separate and sequential use, by determining the optimal vaccination schedule in adult patients with chronic obstructive pulmonary disease (COPD) and to investigate adaptive immunity levels. The clinical effects of vaccination were evaluated in patients with COPD within 1 and 4 years after immunization against pneumococcal infection using various schemes, as well as the time course of changes in adaptive immunity indicators was examined. Four years after vaccination, the 13-valent pneumococcal conjugate vaccine (PCV13)/23-valent pneumococcal polysaccharide vaccine (PPV23) group showed a decline in the number of patients with COPD exacerbations by 50% (p<0.001) and reductions in the number of antimicrobial chemotherapy cycles by 47.8% (p<0.001) and in that of hospitalizations by 87.5% (p<0.001). At 1 year after vaccination versus at baseline, the COPD patients vaccinated against pneumococcal disease, regardless of the drug and schedule of vaccination, displayed elevated levels of IgG antibodies to the mixture of capsular polysaccharides included in PPV23 and PCV13. It has been indicated that a complex of basic therapy for patients with COPD should include initial vaccination with PCV13, followed by administration of a booster dose of PPV23.

Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.

The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses. However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals. We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs. IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides. Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally. HIV-1 gp120 proteins were used to compete for binding to the array. Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection. However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids. Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs. HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans. Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.

Association Between Serum Antibodies to Periodontal Bacteria and Rheumatoid Factor in the Third National Health and Nutrition Examination Survey.

Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population based. This study was undertaken to investigate the association between elevated serum levels of IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults. The Third National Health and Nutrition Examination Survey (NHANES-III) is a cross-sectional sample of the noninstitutionalized US population (n = 33,994). Our study population included all dentate participants who were 60 years and older, did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n = 2,461). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) summarizing the relationship between the 19 periodontal serum IgG antibodies and RF seropositivity ranged from 0.53 (95% CI 0.29-0.97) to 1.27 (95% CI 0.79-2.06), and 17 of the 19 observed ORs were <1.0. The ORs for RF seropositivity among participants with elevated Prevotella intermedia (0.53 [95% CI 0.29-0.97]) and Capnocytophaga ochracea (0.54 [0.31-0.95]) IgG levels were statistically significant. Our findings indicate that elevated levels of IgG antibodies to periodontal bacteria are mostly unassociated with RF seropositivity in the nationally representative NHANES-III. Elevated levels of antibodies to P intermedia and C ochracea are associated with lower odds of RF seropositivity.

Immunogenicity studies of proteins forming the T4 phage head surface.

Advances in phage therapy and novel applications of phages in biotechnology encourage interest in phage impact on human and animal immunity. Here we present comparative studies of immunogenic properties of T4 phage head surface proteins gp23*, gp24*, Hoc, and Soc, both as elements of the phage capsid and as isolated agents. Studies comprise evaluation of specific antibodies in the human population, analysis of the proteins' impact on the primary and secondary responses in mice, and the effect of specific antibodies on phage antibacterial activity in vitro and in vivo in mice. In humans, natural antibodies specific to T4-like phages were abundant (81% of investigated sera). Among those, significantly elevated levels of IgG antibodies only against major head protein (gp23*) were found, which probably reflected cross-reactions of T4 with antibodies induced by other T4-like phages. Both IgM and IgG antibodies were induced mostly by gp23* and Hoc, while weak (gp24*) and very weak (Soc) reactivities of other head proteins were noticed. Thus, T4 head proteins that markedly contribute to immunological memory to the phage are highly antigenic outer capsid protein (Hoc) and major capsid protein (gp23*). Specific anti-gp23* and anti-Hoc antibodies substantially decreased T4 phage activity in vitro and to some extent in vivo. Cooperating with antibodies, the immune complement system also contributed to annihilating phages. Current descriptions of phage immunogenicity and its biological consequences are still vague and incomplete; thus, the central problem of this work is timely and may have strong practical implications. Here is presented the very first description of the contribution of bacteriophage proteins to immunological memory of the phage. Understanding of interactions between phages and mammalian immunology may help in biotechnological adaptations of phages for therapeutic requirements as well as for better appreciation of phage ecology and their role in the biosphere.

Increased Prevalence of Antibodies Against Dietary Proteins in Children and Young Adults With Cerebral Palsy

Undernourishment is common in children with cerebral palsy (CP), but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE antibodies against wheat and gluten. Sera from 99 cases with CP and 99 healthy, age- and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay for detection of IgG antibodies against β-lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG, and IgE antibodies against gluten and wheat. Compared with controls, the odds ratio in cases with CP for having elevated levels of IgG antibodies against β-lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein 11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP subtypes had significantly higher frequencies of elevated levels for all of the tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly lower weight was seen in cases with CP with positive versus negative serology. Elevated levels of IgG against dietary antigens were more frequent in the CP group compared with controls, and particularly in the tetraplegic and dyskinetic CP subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.

IgA antibodies in persisting Helicobacter pylori infection in Finnish adults

Most individuals infected with Helicobacter pylori have elevated levels of specific IgG antibodies, but only in about two-thirds of cases does the IgA titre exceed the cut-off level. The aim of this study was to determine whether H. pylori-infected subjects with elevated IgG levels would subsequently produce IgA antibodies, and whether elevated IgA levels increased during infection. Paired sera were available from 336 adults who took part in a large population-based health survey in 1977-1980 and a follow-up study on asthma and atopic diseases in 1997-1998 (series A). Data on paired sera from 224 adults who participated in a population-based health survey in Vammala, Finland in 1973 and who gave a follow-up blood sample in 1994 (series B) were also re-analysed. H. pylori IgG and IgA levels were determined with commercially available (series A) and in-house (series B) enzyme immunoassays. Twenty-one (35%) of the 60 subjects who initially had elevated levels of IgG antibodies only were found to be IgA-positive at follow-up. In those subjects whose baseline and follow-up samples were IgG- and IgA-positive, the median IgA levels increased by 48% and 22% in series A and B (p < 0.0001 and p 0.0241), respectively, whereas the median IgG levels did not change significantly in either series. During H. pylori infection, an increase in specific IgA was reflected by the increase in the number of responders and by the rise in titres.

A comparative analysis of antibody repertoire against Staphylococcus aureus antigens in Patients with Deep-Seated versus Superficial staphylococcal Infections

Immunoblot and an enzyme-linked immunosorbent assays were used to evaluate and compare IgG antibodies against S. aureus whole cell lysate, cell wall peptidoglycan and lipoteichoic acid to discriminate between deep-seated and superficial S. aureus infection. Serum samples were examined from patients with deep-seated (n = 25) and superficial (n = 25) S. aureus infections and 15 healthy controls. Patients with deep-seated infections exhibited a large number of immuno-reactive bands in their IgG immunoblot profile as compared to those with superficial infections and healthy controls. Anti-staphylococcal IgG antibodies that reacted with two antigens of apparent molecular weight 110 and 98 kDa were specifically present in 96% (24/25) of patients with deep-seated infections, and were absent in, superficial and control sera. Moreover other Gram-positive and Gram-negative bacteria did not share these two unique antigens. The ELISA assays revealed significantly elevated levels of IgG antibodies to peptidoglycan (PG) in 18 of 25 (72%) patients with deep infection and 15 of 25 (60%) patients with superficial staphylococcal infection. The elevated levels of IgG antibodies to teichoic acid (TA) antigen were detected in all (100%) deep-seated group patients and among 40% (10/25) patients with superficial infection. An increase in levels of antibodies to PG showed a positive correlation trend with levels of IgG antibodies to TA only in deep infection group. Thus immunoblot detection of these two unique antigens as well as detection of elevated antibodies against PG and TA may be useful for the discrimination of staphylococcal deep-seated and superficial infection in humans.

The effect of oxfendazole terminated infections with Haemonchus contortus on the development of immunity in sheep

The relative contribution of third (L3), fourth (L4) or adult stages of Haemonchus contortus to the development of immunity was evaluated in three groups of sheep subjected to infections terminated by oxfendazole treatments at the L3, L4 or adult stage. A control group did not receive immunising infections. All the groups were challenged with 5000 L3, to evaluate the protection provided by the different protocols. All sheep were necropsied at the end of the experiment to count the abomasal worm burdens. A marked reduction in egg counts after challenge infection was only observed in sheep in which the infection was terminated in the adult stage (Group 4). A significant reduction in worm burden was also observed in Group 4. The immunising infections and/or the challenge infection resulted in moderately elevated IgG antibody levels against L3, L4 and adult somatic antigens in all the groups. In contrast, a strong IgG response against H. contortus excretory/secretory (ES) antigens was observed in the groups in which the immunising infection was terminated in the L4 and the adult stage. An elevated lymphocyte proliferation response against Haemonchus ES antigens was found only in the group that had their immunising infection terminated at the adult stage. The combined data suggest that exposure to and elicited immunological responses to ES antigens are important for the development of immunity against H. contortus.

Asthma, atopy and Chlamydia pneumoniae antibodies in adults.

Factors involved in the development of inflammation and asthma in nonatopic subjects have remained largely obscure, although there is some evidence to suggest that certain infections may play a role. We investigated the association between serological evidence of Chlamydia pneumoniae infection and asthma in adults, and the possible modifying effect of the patients' atopic status on this association. Four hundred and thirty consecutive patients who attended the hospital between 1992 and 1993 with symptoms suggestive of asthma, rhinitis or allergy were enrolled. Diagnostic procedures including lung function measurements and skin-prick tests were performed in all patients. The patients with established asthma (n = 332) were divided into those with recent asthma (n = 224, onset 1985 onward) and longstanding asthma (n = 108, onset before 1985). The controls (n = 98) comprised all subjects who did not meet the criteria of asthma. Serum immunoglobulin (Ig)G, IgA and IgM antibodies to C. pneumoniae were measured by the microimmunofluorescence test. In women, the prevalences of elevated IgG (a titre of >/= 128) and IgA (>/= 32) antibody levels and the age-adjusted geometric mean titres (GMT) of IgG and IgA antibodies were invariably highest among subjects with nonatopic longstanding asthma. Elevated IgG titres in women occurred in 11% of controls, in 28% of nonatopic recent onset asthmatics, and in 43% of asthmatics with nonatopic longstanding disease; for men the respective figures were 33, 50 and 64%. Logistic regression analysis controlling for age, sex and smoking showed that asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae (odds ratio 3.3, 1.6-6.8 for longstanding asthma, 2.3, 1. 2-4.4 for recent asthma, and among women only 4.2, 1.6-10.9 for longstanding asthma, and 3.0, 1.3-7.2 for recent asthma). When the atopics and nonatopics were analysed separately, an even stronger relationship in the nonatopics was obtained for longstanding asthma (6.0,2.1-17.1). In contrast, the relationship between atopic asthma, either recent or longstanding, and elevated IgG titres was not significant, indicating that asthma per se does not predispose to C. pneumoniae infection. Asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae, and this association was strongest for nonatopic longstanding asthma.

Comparison of IgE and IgG antibody responses of atopic individuals with sensitization to tree and grass pollens

Sera of atopic individuals with predominant sensitization to either tree pollen (TAs) or tree and grass pollens (TGAs) as well as of nonatopic subjects (NAs) were analyzed for IgE, IgG, and IgG4 antibodies specific for grass pollens allergens. Of 600 atopic individuals with serum IgE antibodies specific for birch pollen allergens, 54% also had serum IgE antibodies specific for grass pollen. The mean titers of IgG antibodies specific for grass pollen proteins were about 10 times higher in the sera of TGAs than those in the TAs and NAs. SDS-PAGE immunoblotting analysis of grass pollen proteins using sera of TGAs, TAs, and NAs with respect to the binding of these proteins with IgE and IgG antibodies in these sera exhibited a similar pattern of variation. Quantitation by enzyme immunoassay of the antibody binding to a recombination grass pollen allergen, rKBG8.3, further demonstrated the elevated IgG antibody levels in TGAs are mainly due to a broader range of specificities, and not to high specific binding to the individual protein. Statistically significant correlation was found between IgE and IgG4 antibodies specific for the Kentucky bluegrass (KBG) extract, but not for the isolated recombinant allergen. These results indicate that the grass pollens elicit a complex array of antibody specificities in both atopics and nonatopics, and that the profile of antibodies specific to the pollen extract and pure allergens differs, suggesting that single grass allergens may be inadequate for replacing grass pollen extracts for immunotherapy.

Antibodies to the 70-kDa Heat-Shock Protein in Patients with Thermal Burns

Autoantibodies in the sera of patients with thermal burns, which hind to a protein in the intercellular substance of the epidermis, have been previously described. By immunoblot analysis, we have shown that a 68-kDa epidermal protein is the predominant antigen to which these autoantibodies bind. Our study also demonstrates that this 68-kDa epidermal protein is similar to the bovine brain 70-kDa heat-shock protein (hsp 70). In addition, we have detected significantly elevated levels of IgG antibodies to the bovine brain hsp 70 in all of the sera from random burned patients ( n = 33), in comparison with the levels in the sera of normal, healthy controls ( n = 43, P < 0.0001). The precise role and significance of these autoantibodies and their influence on the immune system in burned patients remain to be determined.

Toluene diisocyanate–induced reverse passive cutaneous anaphylaxis caused by IgG antibody

Toluene diisocyanate (TDI)-induced asthma is a complex lung disease not easily classified as immunologic in pathogenesis. In one study IgE antibodies were demonstrated in approximately 92% of patients. 1 Other studies reported a much lower incidence of IgE antibodies present in subjects (15% to 19%). 2 A reactive airways dysfunction syndrome has also been described, for which no immunologic mechanism has been found? Elevated levels of IgG antibodies have been correlated with isocyanate-induced asthma. 4 Classically, IgG antibodies are not associated mechanistically with extrinsic asthma. However, in vitro analysis has shown that IgG antibodies could activate haptenized basophils. 5 We postulated that IgG antibodies might activate mast cells modified by isocyanate haptenization. Such a phenomenon might have a correlation with certain human cases of TDI-induced asthma. In this study we attempted to determine whether IgG antibodies could generate a reverse passive cross-species cutaneous anaphylactic reaction against TDI.

Tick-borne Borreliosis in the Archipelage of Southern Sweden

Sera from 480 individuals living on an island at the Baltic coast in southern Sweden were tested by ELISA for detection of antibodies against Borrelia burgdorferi. The area was found to be highly endemic for Lyme borreliosis with elevated IgG antibody levels in 90/480 individuals (19%). Of 149 ticks collected on the island 16 nymphs (17%) and 15 adults (26%) were infected by B. burgdorferi. The occurrence of antibodies to B. burgdorferi increased with age and time spent in the endemic area. Infection without manifest disease seemed to dominate since only 18/480 (4%), or 6/90 (7%) with positive serology, had been treated for Lyme borreliosis. However, the prevalence of symptoms associated with late manifestations of Lyme borreliosis e.g. arthralgia, chronic skin efflorescences or neurologic disorders was significantly higher among seropositive compared to seronegative individuals.