The allergy adjuvant effect of particles – genetic factors influence antibody and cytokine responses

BACKGROUND: There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated) and IgG2a (Th1-associated) responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP) affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA), after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-γ and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN) five days after injection of OVA and PSP separately or in combination was determined. RESULTS: PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-γ levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-γ in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only). CONCLUSION: Genetic factors (i.e. the strain of mice) influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that the ex vivo cytokine patterns did not predict the in vivo Th2- and Th1-associated antibody response patterns in the different mouse strains. The results indicate that insoluble particles act by increasing the inherent response to the allergen, and that the genetic background may determine whether an additional Th1-associated component is added to the response

Actividad opsonofagocítica contra meningococos del grupo B:¿Un correlato de protección adicional contra la enfermedad meningococica?

Opsonophagocytic activity and serum bactericidal activity against group B meningococci were compared in sera from three vaccine groups given two different outer membrane vesicles vaccines separately or in combination. Opsonophagocytic activity defined more responders and revealed more cross-reactivity against heterologous strains than observed with serum bactericidal activity, and it showed the highest correlation with IgG-binding to live meningococci. Determination of opsonophagocytic activity may therefore be a valuable laboratory supplement to serum bactericidal activity for monitoring protection against group B meningococcal disease

Human seroprevalence of antibodies to tick-borne microbes in southern Norway

The tick Ixodes ricinus is widespread along the coastline of southern Norway, but data on human exposure to tick-borne microbes are scarce. We aimed to assess the seroprevalence of IgG antibodies to various tick-borne microbes in the general adult population living in a Norwegian municipality where ticks are abundant. Søgne is a coastline municipality in the southernmost part of Norway, and has a high density of ticks. All individuals aged 18-69 years with residential address in Søgne municipality (n = 7424) were invited to give a blood sample and answer a questionnaire. Blood samples from 3568 individuals were available for analysis. All samples were analyzed for IgG antibodies to Borrelia burgdorferi sensu lato (Bbsl), and around 1500 samples for IgG antibodies to other tick-borne microbes. Serum IgG antibodies to Bbsl were present in 22.0% (785/3568) of the tested samples, tick-borne encephalitis virus (TBEV) in 3.1% (45/1453), Anaplasma phagocytophilum in 11.0% (159/1452), Babesia microti in 2.1% (33/1537), Bartonella henselae/B. quintana in 0.1% (2/1451) and Rickettsia helvetica/R. conorii in 4.2% (60/1445). Serum IgG antibodies to A. phagocytophilum and R. helvetica/R. conorii were significantly more prevalent (p = 0.010 and p = 0.016, respectively) among individuals with serum IgG antibodies to Bbsl than among individuals without. In conclusion, our study showed a high exposure to Bbsl in the general adult population living in a coastline municipality in the southernmost part of Norway. The population is also exposed to A. phagocytophilum, R. helvetica/R. conorii, B. microti and TBEV, but very rarely B. henselae/B. quintana

Protection by Natural Human Immunoglobulin M Antibody to Meningococcal Serogroup B Capsular Polysaccharide in the Infant Rat Protection Assay Is Independent of Complement-Mediated Bacterial Lysis

Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease develops with age, but the specificity and functional activity of natural antibodies associated with protection are poorly understood. We addressed this question by using a selected subset of prevaccination sera (n = 26) with convergent or discrepant serum bactericidal activity (SBA) and infant rat protective activity (IRPA) against the serogroup B meningococcal strain 44/76-SL (B:15:P1.7,16) from Icelandic teenagers (B. A. Perkins et al., J. Infect. Dis. 177:683-691, 1998). The sera were analyzed by opsonophagocytic activity (OPA) assay, immunoblotting, immunoglobulin G (IgG) quantitation against live meningococcal cells by flow cytometry, and enzyme immunosorbent assay (EIA). High levels of SBA and OPA were reflected in distinct IgG binding to major outer membrane proteins and/or lipopolysaccharide in immunoblots. However, we could not detect any specific antibody patterns on blots that could explain IRPA. Only IgM antibody to group B capsular polysaccharide (B-PS), measured by EIA, correlated positively (r = 0.76, P < 0.001) with IRPA. Normal human sera (NHS; n = 20) from healthy Finnish children of different ages (7, 14, and 24 months and 10 years) supported this finding and showed an age-related increase in IRPA that coincided with the acquisition of B-PS specific IgM antibody. The protection was independent of complement-mediated bacterial lysis, as detected by the inability of NHS to augment SBA in the presence of human or infant rat complement and the equal protective activity of NHS in rat strains with fully functional or C6-deficient complement

Subjective health complaints and exposure to tick-borne infections in southern Norway

Objectives Whether tick‐borne infections can cause chronic subjective health complaints is heavily debated. If such a causal connection exists, one would expect to find more health complaints among individuals exposed to tick‐borne infections than among non‐exposed. In this study, we aimed to assess if exposure to tick‐borne infections earlier in life, evaluated by examination of serum for IgG antibodies to tick‐borne microbes, was associated with self‐reported somatic symptom load. Materials & Methods All individuals with residential address in Søgne municipality in southern Norway, aged 18‐69 years, were invited to participate in the study. Blood samples were analyzed for IgG antibodies to different tick‐borne microbes, and somatic symptom load was charted by the Patient Health Questionnaire‐15 (PHQ‐15). Results Out of 7424 invited individuals, 2968 (40.0%) were included in the study. We detected IgG antibodies to Borrelia burgdorferi sensu lato (Bb) in 22.9% (95% CI 21.4‐24.4). Bb seropositive individuals reported less frequently moderate to severe somatic symptom load (ie, PHQ‐15 sum score ≥ 10) than seronegative individuals (12.5% versus 17.7%, difference 5.2% [95% 2.1‐8.0]). However, when adjusting for several other variables in a multivariable linear regression model, presence of serum IgG antibodies to Bb was not associated with somatic symptom load. Presence of IgG antibodies to other tick‐borne microbes than Bb, or seropositivity to at least two microbes, was also not associated with somatic symptom load. Conclusion Presence of serum IgG antibodies to tick‐borne microbes was not associated with self‐reported somatic symptom load