Changes In Autoantibody Levels Research Articles

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms

ObjectiveThis retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). MethodsIn an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as “Improved/Resolved” (n = 34) or “Not-Improved/Worsened” (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. ResultsComparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10−6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. ConclusionThis study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.

In rheumatoid arthritis, changes in autoantibody levels reflect intensity of immunosuppression, not subsequent treatment response

BackgroundRheumatoid arthritis (RA) is characterized by the presence of autoantibodies like rheumatoid factor (RF), anti-cyclic citrullinated peptide-2 (anti-CCP2), and anti-carbamylated protein (anti-CarP) antibodies. It is currently unclear whether changes in autoantibody levels are associated with disease activity/treatment outcomes and whether they are modified by treatment intensity. Therefore, we determined longitudinal changes in RA-autoantibody levels, the association between these changes and activity score (DAS) and treatment outcomes, and the effect of intensity of immunosuppressive treatment on levels.MethodsIn 381 seropositive RA patients from the IMPROVED study, we measured IgG, IgM, and IgA of anti-CCP2 and anti-CarP; IgM and IgA of RF; and IgG against four citrullinated and two acetylated peptides at 4-month intervals over the first year of treatment. Following initial prednisone and methotrexate (MTX), treatment was changed every 4 months aiming for DAS < 1.6. We investigated changes in autoantibody levels following treatment escalation versus tapering, and the association of levels with DAS over time, EULAR response, and drug-free remission (DFR) ≥ 1 year.ResultsFor all 14 autoantibodies, levels decreased from 0 to 4 months and then rose until 12 months. Following treatment escalation, autoantibody levels dropped markedly, while they rose following tapering: RF IgM levels, a representative autoantibody, dropped 10% after restarting prednisone and rose 15% aU/mL after tapering MTX (p < 0.0001). There was no association between autoantibody levels and DAS over time or EULAR response. Greater relative changes between 0 and 12 months did not predict DFR (0–12-month relative change RF IgM, − 39% for no DFR (n = 126) and − 16% for DFR (n = 18)).ConclusionsChanges in RA-autoantibody levels are not associated with DAS or long-term treatment response, but reflect intensity of immunosuppression. This suggests that autoantibody levels are modifiable by current therapies, but that modifying levels is in itself of limited clinical relevance.Trial registrationISRCTN11916566. Registered on 7 November 2006

Membranous Nephropathy: Pilot Study of a Novel Regimen Combining Cyclosporine and Rituximab

IntroductionThere is broad consensus that high-grade basal proteinuria and failure to achieve remission of proteinuria are key determinants of adverse renal prognosis in patients with primary membranous nephropathy. Since current regimens are not ideal due to short- and long-term toxicity and propensity to relapse after treatment withdrawal, we developed a treatment protocol based on a novel combination of rituximab and cyclosporine that targets both the B-cell and T-cell limbs of the immune system. Herein, we report pilot study data on proteinuria and changes in autoantibody levels and renal function that offer a potentially effective new approach to treatment of severe membranous nephropathy.MethodsThirteen high-risk patients defined by sustained high-grade proteinuria (mean 10.8 g/d) received combination induction therapy with rituximab plus cyclosporine for 6 months, followed by a second cycle of rituximab and tapering of cyclosporine during an 18-month maintenance phase.ResultsMean proteinuria decreased by 65% at 3 months and by 80% at 6 months. Combined complete or partial remission was achieved in 92% of patients by 9 months; 54% achieved complete remission at 12 months. Two patients relapsed during the trial. All patients with autoantibodies to PLA2R achieved antibody depletion. Renal function stabilized. The regimen was well tolerated.DiscussionWe report these encouraging preliminary results for their potential value to other investigators needing prospectively collected data to inform the design and power calculations of future randomized clinical trials. Such trials will be needed to formally compare this novel regimen to current therapies for membranous nephropathy.

Gender differences at baseline in autoantibody levels but no gender differences in vaccine-induced responses and no changes in autoantibody levels following influenza vaccine (HUM6P.246)

Abstract Background. Gender bias presents in most autoimmune diseases such as systemic lupus erythematosus (SLE) disease. In the current study, we investigate the mechanisms of gender bias in autoreactive antibody (Ab) production in healthy controls after influenza (flu) vaccination. Method. Plasma levels of anti-nuclear Ab (ANA), anti-dsDNA autoAb, and anti-CD4 autoAb in a cohort of 5 healthy men and 11 healthy women received vaccines at 2012-2013 and 2013-2014 seasons. Blood draws were taken at 0, 7, and 14 days after the latest vaccination. Vaccine responses were defined by neutralization activities in plasma. Flu-specific Ab avidity was tested by ELISA. The levels of autoAbs were analyzed in plasma by ELISA. Results: Women have higher levels of all 3 autoAbs than men at D0, but not the flu-specific neutralizing activities or flu-specific Ab avidities. The median plasma levels of anti-ANA Ab (OD) at D0 were 0.2281 (IQR, 0.2058 - 0.2338) and 0.3697 (IQR, 0.2918 - 0.4261); the median plasma levels of anti-CD4 Ab (OD) were 0.1678 (IQR, 0.1589 - 0.1932) and 0.2148 (IQR, 0.1986 - 0.2696); and the median plasma levels of anti-dsDNA Ab (IU/mL) were 122.3 (IQR, 91.86 - 175.8) and 197.3 (IQR, 131.2 - 389.8), for men and women respectively (P &amp;lt; 0.05, Mann Whitney U test). Influenza vaccination did not change the titer of autoAbs at any time point. Conclusions: Women have increased levels of autoAbs than men, and these autoAbs are not resulted from repeated influenza vaccinations.

AB0271 Changes of serological markers in early and established rheumatoid arthritis (RA) during the course of traditional and biological disease modifying therapy

BackgroundRheumatoid factor (RF) and antibodies to citrullinated peptides (ACPA) are established markers in the diagnostic and prognostic approach to RA1. Several studies have examined changes of RF during therapy, but...

Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy

Objectives:To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the...

Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis

Background Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFα antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy. Methods Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3 mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined. Results At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly ( p < 0.001), whereas anti-CCP showed little change ( p = 0.053). ANA titres increased significantly ( p < 0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16–3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16–4.13]). Conclusions During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.

B Lymphocyte Depletion with the Monoclonal Antibody Rituximab in Graves’ Disease: A Controlled Pilot Study

Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might be of benefit in GD. The objective of this prospective, controlled, nonrandomized study was to investigate the effect of RTX in GD. We studied 20 outpatients referred to a university clinic with newly diagnosed (four with relapse) untreated GD. Ten received RTX (+RTX), whereas 10 did not (-RTX). The patients received methimazole (MMI) for a median of 102 d (+RTX) and 110 d (-RTX) before the study. Patients in the +RTX group received 375 mg RTX/m(2) iv on d 1, 8, 15, and 22, and all patients were withdrawn from methimazole (MMI) at d 22. We measured time to relapse of hyperthyroidism and changes in autoantibody levels. Four patients in the +RTX group remained in remission with a median follow-up of 705 d (range, 435-904 d), whereas all the patients in the -RTX group had relapsed by d 393 (P < 0.05). All of the patients in remission had initial TRAb levels below 5 IU/liter (normal, <0.7 IU/liter). However, none of the five patients in the -RTX group with correspondingly low TRAb levels were in remission (P < 0.01). RTX treatment did not affect autoantibody levels to a greater extent than did MMI monotherapy. Two patients received glucocorticoids for joint pain after RTX therapy. RTX treatment may induce sustained remission in patients with GD with low TRAb levels. However, RTX did not affect autoantibody levels and seems ineffective in patients with high TRAb levels. At present, high cost, low efficacy, and potential side effects do not support use in uncomplicated GD.

Quantitation of Autoantibodies in Systemic Autoimmune Diseases: Clinically Useful?

Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much controversy exists, however, concerning the value of serial testing in these diseases. We here review the various tests available for quantitation of anti-dsDNA and ANCA, and their capacity to detect changes in autoantibody levels that are associated with changes in clinical disease activity of the respective diseases. It is concluded that changes in anti-dsDNA as measured by the Farr assay and changes in ANCA as assessed by ELISA have predictive value for the occurrence of disease relapses, although this relationship is far from absolute. Consequently, treatment based on changes in levels of the respective autoantibodies only seems at present not justified, in view of the toxicity of currently available immunosuppressive regimens.

Specific changes in levels of autoantibodies to glutamate and opiate receptors induced by morphine administration in rats

Several groups of brain receptors are involved in the mechanisms underlying the development of opiate addiction, but the interactions occurring between these neuroreceptors and the immune system, including potential autoimmune responses, remain poorly understood. We studied in rats the effects of repeated administration of different psychotropic drugs on serum levels of autoantibodies (aAbs) to the mu delta-opiate receptor (MDOR), as well as to the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) GluR1 and to the N-methyl- d-aspartate (NMDA) NR2 subunits of the glutamate receptor, as analyzed by ELISA. We found that repeated administration of morphine significantly elevated aAbs levels to MDOR and to the AMPA GluR1 subunit, but not to the NMDA NR2 subunit. In contrast, a similar regimen of a psychostimulant drug, such as d-amphetamine, or a commonly abused substance, such as nicotine, had no effect on these aAbs levels. A nonspecific elevating effect on aAbs to the brain structural protein S100B was observed for all drugs tested versus controls. These observations support the hypothesis that, following opiate administration, specific interactions between nervous and immune systems occur. Therefore, together with further investigations on their potential functional consequences, we propose a thorough exploration of aAbs to MDOR and to AMPA GluR1 subunit as early biomarkers signaling opiate addiction.

The relationship between in vitro fertilization and naturally occurring antibodies: evidence for increased production of antiphospholipid autoantibodies

Assessment of possible effects of ovarian stimulation during in vitro fertilization (IVF) treatment cycles on circulating levels of antiphospholipid and antinuclear autoantibodies. The study was performed prospectively. Sera were obtained at three time points along IVF treatment cycle. Levels of autoantibodies directed against nuclear components, mitochondrial antigens, and phospholipids were determined using enzyme-linked immunosorbent assay. Thirty-five patients, who underwent at least one previous IVF attempt, and 36 age- and sex-matched controls were analyzed. All participants were randomly selected. The mean levels of antiphospholipid (but not antinuclear) autoantibodies in sera from IVF-treated patients were found to be significantly higher than the corresponding values of the control group (for immunoglobulin [Ig]M isotype: anticardiolipin, antiphosphatidyl L-serine; for IgG isotype: anticardiolipin, antiphosphatidyl L-serine, and antiphosphatidylcholine; P less than 0.0001, assessed by Mann-Whitney test). The autoantibody levels remained more or less constant at different time points along the treatment cycle. No correlation with age and number of previous IVF cycles was demonstrated. Serum levels of antiphospholipid (but not antinuclear) autoantibodies increase after IVF treatment. Based on these preliminary data, it is not yet possible to estimate if the observed changes in autoantibody levels might have any future clinical influence on infertile patients undergoing IVF treatment.