Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis

Objectives: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. Materials and Methods: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. Results: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (P=0.0096) and 3.00 (P=0.0198), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (odds ratio 4.56; P=0.0076). Clinical Significance: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis

Objectives: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. Materials and Methods: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. Results: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (P=0.0096) and 3.00 (P=0.0198), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (odds ratio 4.56; P=0.0076). Clinical Significance: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.This study was funded by PetSavers, the charitable division of the BSAVA, and by The Wellcome Trust (Grants 092805 and 202789 awarded to HJW).https://onlinelibrary.wiley.com/journal/17485827Companion Animal Clinical Studie

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Association of smoking with triple concordant seropositivity in RA patients, and with rheumatoid factor in the remaining patients

Background: The contribution of cigarette smoking to the risk of rheumatoid arthritis (RA) is larger for seropositive than for seronegative patients. Current pathogenic models explain this difference via the production of anti-citrullinated protein antibodies (ACPA) induced by protein citrullination in the lungs as a consequence of smoking. However, there are inconsistent results with this model including the van Wesemael et al . report, which found an association of smoking with the concurrent presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein antibodies (ACarPA), rather than with ACPA. Objectives: We aimed to explore the relationship between smoking and the presence of FR, ACPA and ACarPA and their combinations in patients with RA. Methods: Six cohorts with 2253 RA patients were obtained to replicate the van Wesemael et al . results. After replication, they were combined with the three cohorts from that study comprising 2238 patients to a total of 4491 patients. The results from the different cohorts were combined by fixed-effects meta-analysis. Most analyses involved comparisons between two levels of smoking exposure, never and ever smokers, considering the RF-/ACPA-/ACarP-patients as the reference. Results: Analysis of the replication set confirmed the predominant association of smoking with the concurrent presence of the three RA autoantibodies (OR = 1.99, P = 2.5 x 10-8), whereas the patients with one or two antibodies were not different from the patients without antibodies (OR = 1.22, p = 0.4 and OR = 1.22, p = 0.3, respectively). The combined meta-analysis with all the cohorts clarified the dominant association of smoking with the triple concordant seropositivity (OR = 2.00, p = 4.4 x 10-16). In contrast, there was no association with the patient bearing one autoantibody (OR = 1.12, p = 0.4), and an in-between association with the concurrent presence of two antibodies (OR = 1.26, p = 0.009). Moreover, the association with the presence of three antibodies was significantly larger than with two antibodies (OR = 1.54, p = 1.4 x 10-6), whereas the association with the presence of two antibodies was not larger than with one autoantibody (OR = 1.11, p = 0.3). In the patients remaining after exclusion of the triple seropositive, the smokers were exclusively associated with the RF+ (OR = 1.28, p = 0.03 and OR = 1.30, p = 0.004 in the double and single positive patients, respectively). This association was independent of the reference, either the triple seronegative (OR = 1.29, p = 0.001) or all the RF-patients (OR = 1.32, p = 0.0002). Conclusion: Smoking increases RA susceptibility by promoting pathways leading to the concurrent presence of the three RA autoantibodies and, in its defect, to the production of RF. These actions are not covered by current pathogenic models and suggest that smoking accelerates epitope spread

HLA-B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis

Objective. Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA.Methods. Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for similar to 8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 x 10(-5).Results. The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 x 10(-7); I-2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium.Conclusion. These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.Pathophysiology and treatment of rheumatic disease