Antibodies In Healthy Controls Research Articles

Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy.

Immunoglobulin replacement therapy is a mainstay therapy for patients with primary immunodeficiency (PID). The content of these preparations was studied extensively. Nevertheless, data regarding the effective specific antibodies content (especially in the nadir period), and, in different groups of PID patients is limited. We studied trough IgG concentrations as well as anti-Pneumococcus, anti-Haemophilus influenzae b, anti-Tetanus, and anti-Measles antibody concentrations in 17 PID patients receiving intravenous immunoglobulin (IVIg) compared with healthy controls matched for age and ethnicity. We also analyzed these results according to the specific PID diagnosis: X-linked agammaglobulinemia (XLA), combined immunodeficiency (CID), and ataxia telangiectasia (AT). We recorded a higher concentration of anti-pneumococcal polysaccharide antibodies in healthy controls compared to the entire group of PID patients. We also found significantly higher anti-tetanus toxoid antibody concentrations in the XLA patients, compared to CID patients. Anti-Haemophilus Influenzae b antibody titers were overall similar between all the groups. Interestingly, there were overall low titers of anti-Measles antibodies below protective cutoff antibody concentrations in most patients as well as in healthy controls. We conclude that relying on total IgG trough levels is not necessarily a reflection of effective specific antibodies in the patient’s serum. This is especially relevant to CID patients who may have production of nonspecific antibodies. In such patients, a higher target trough IgG concentration should be considered. Another aspect worth considering is that the use of plasma from adult donors with a waning immunity for certain pathogens probably affects the concentrations of specific antibodies in IVIg preparations.

Association among serum and salivary A. actinomycetemcomitans specific immunoglobulin antibodies and periodontitis

BackgroundThe aim of this study was to assess the association between serum and salivary Immunoglobulin (Ig) Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) specific antibodies in healthy controls (HC) and periodontitis (PT) patients. Furthermore, the objectives were to determine whether PT influenced serum A. actinomycetemcomitans specific antibodies and whether serum or salivary antibodies against A. actinomycetemcomitans IgG were mediated by serum high-sensitivity c-reactive protein (hs-CRP).MethodsFifty-three patients with periodontitis and 48 HC were enrolled in the present study. Patients were regularly examined and characterized by clinical, salivary and blood samples analyses. A. actinomycetemcomitans IgA and IgG antibodies and hs-CRP were evaluated using a commercially available kit. The Spearman Correlation Test and Jonckheere-Terpstra Test were applied in order to assess the interdependence between serum A. actinomycetemcomitans IgG antibodies and clinical periodontal parameters. To evaluate the dependence of the serum and salivary A. actinomycetemcomitans IgG levels from possible confounders, univariate and multivariable linear regression analyses were performed.ResultsCompared to HC, patients with PT had significantly higher IgA [serum: PT, 1.89 (1.2–2.2) EU vs HC, 1.37 (0.9–1.8) EU (p = 0.022); saliva: PT, 1.67 (1.4–2.1) EU vs HC, 1.42 (0.9–1.6) EU (p = 0.019)] and A. actinomycetemcomitans IgG levels [serum: PT, 2.96 (2.1–3.7) EU vs HC, 2.18 (1.8–2.1) EU (p < 0.001); saliva, PT, 2.19 (1.8–2.5) EU vs HC, 1.84 (1.4–2) EU (p = 0.028)]. In PT patients, serum A. actinomycetemcomitans IgG were associated with a proportional extent of PT and tooth loss (P-trend value< 0.001). The univariate regression analysis demonstrated that PT (p = 0.013) and high hs-CRP (p < 0.001) had a significant negative effect on serum and salivary A. actinomycetemcomitans IgG levels. The multivariate regression analysis showed that PT (p = 0.033), hs-CRP (p = 0.014) and BMI (p = 0.017) were significant negative predictors of serum A. actinomycetemcomitans IgG while hs-CRP (p < 0.001) and BMI (P = 0.025) were significant negative predictors of salivary A. actinomycetemcomitans IgG.ConclusionsPT patients presented a significantly higher serum and salivary A. actinomycetemcomitans IgA and IgG compared to HC. There was a significant increase in serum A. actinomycetemcomitans IgG when patients presented a progressive extent of PT. Moreover, PT and hs-CRP were significant negative predictors of increased salivary and serum A. actinomycetemcomitans IgG levels.Trial registrationThe study was retrospectively registered at clinicaltrials.gov (NCT04417322).

PS02.052: AUTO-ANTIBODIES AGAINST TUMOR ANIGENS ARE USEFUL BIOMARKERS IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Serum antibodies are induced even ata the eraly phase of carcinogenesis. Serum p53 antibodies (s-p53-Abs) have been developed and approved as routine blood test for monitoring esophageal squamous cell carcinoma (SCC). Recently, we have developed new ELISA systems to detect serum anti-IgG auto-antibodies against tumor antigens in patients with esophageal (SCC). In this paper, we focused on serum auto-antibodies against p53, NY-ESO-1, Galectin-1 and RalA. Methods Serum samples of patients with esophageal SCC were obtained before surgery. Serum anti-IgG antibodies against several tumor antigens were analyzed by newly developed ELISA systems. Target tumor antigens were p53, NY-ESO-1, Galectin-1 and RalA. Cut-off values were fixed using mean + 3SD of values of a total of 74 healthy controls. Changing pattern of serum p53 antibodies titers was also assessed during postoperative follow-up. Results Positive rates of serum antibodies were 18% for p53, 31% for NY-ESO-1, 10% for Galectin-1 and 9% for RalA. Positive rates of these antibodies in healthy controls were 0%. Combination assay improved positive rates without increased false positive rates as follows; p53 + NY-ESO-1 = 40%, p53 + NY-ESO-1 + Galectin-1 = 47%, p53 + NY-ESO-1 + Galectin-1 + RalA = 51%. Although some patients with extremely-high antibody titer for p53 persistently positive even after curative surgery, changing patterns of serum titers seemed to be associated with clinical outcome. Conclusion Although antibody titer of s-p53-Abs seemed to be associated with tumor burden, the titer gradually decresed at the last several months of the terminal stage. Such independent changing pattern of serum autoantibodies may have adding information to conventinal serum markers. We have developed new ELISA system to detect serum autoantibodies for patients with esophageal SCC. Although the positive rates of single serum auto-antibody were still relatively low, combination assay with plural auto-antibodies may be useful. Disclosure All authors have declared no conflicts of interest.

Phosphorylcholine antibodies are diminished in ANCA-associated vasculitis.

ANCA-associated (AAV) vasculitis is an autoimmune small-vessel vasculitis and may be associated with accelerated atherosclerosis as suggested by current literature. Antibodies against oxidized lipoproteins (OxLDL) and phosphorylcholine (Pc) protect from atherosclerosis. This study characterizes these antibodies in AAV. Pc- and anti-OxLDL antibodies were determined in sera of 39 AAV patients and 44 healthy controls (HC). Intima-media thickness (IMT, carotids) and pulse wave velocity (PWV, A. femoralis) were measured. Pc-/OxLDL IgM antibodies were significantly reduced in AAV. IMT and PWV were negatively associated with anti-Pc antibodies in HC only. Atheroprotective anti-Pc/anti-OxLDL antibodies are significantly reduced in AAV possibly explaining accelerated atherosclerosis in vasculitis patients.

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia

Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1. To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus. We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients. Results Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1-positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions. These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

Circulating antibodies to human and bovine cornea in human keratoplasty.

To compare anti-human cornea and anti-bovine cornea serum reactivity in corneal transplantation and pathology. We investigated the presence of IgG and IgM antibodies to bovine corneal extract (BCE) and human corneal extract (HCE) by ELISA in 48 healthy adults and in 30 corneal allograft recipients before and after grafting. Baseline levels of antibodies in healthy controls served to establish a positivity threshold. Anti-HLA antibodies were investigated in all patients. Preoperatively, five and one patient were positive respectively for IgG and IgM anti-BCE; one and ten patients were positive for IgG and IgM anti-HCE. The presence or absence of antibodies was not modified after grafting, and was not associated with rejection. Anti-HCE of the IgM class were more frequent in patients with keratoconus. Two patients had anti-HLA antibodies. Antibodies to non-HLA corneal antigens are detectable in corneal allograft recipients. Reactions against bovine and human substrates differ in frequency and class. This reactivity is not modified after grafting or rejection, but is increased in corneal disorders, including keratoconus.

CD8+ lymphocyte decrease in HIV disease: association with anti-CD4+ but not with anti-CD8+ lymphocyte autoantibodies.

HIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti-CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti-CD4+ and anti-CD8+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti-CD8+ lymphocyte autoantibodies were found more often in HIV + hemophilia patients (75/105 = 71%) than HIV- hemophilia patients (13/37 = 35%; p < 0.0001), patients with pharyngeal carcinoma (20/44 = 45%; P = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93-223 = 42%; p < 0.0001). Anti-CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti-CD4+ antibodies in healthy controls (p < 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV- patients (p = 0.01). In HIV+ patients, however, anti-CD4+ autoantibodies were found more often than anti-CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti-CD4+ (p = 0.01) but not with anti-CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti-CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.