Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype.

We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p=.004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p=.024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606-614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.

The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis.

OBJECTIVES: In primary biliary cirrhosis (PBC), the antimitochondrial antibody is a cornerstone of diagnosis, but there have been conflicting reports about the correlation of autoantibodies with disease stage and prognosis. We studied whether autoantibody levels changed over time and sought correlations with clinical outcomes in a cohort of patients with PBC. METHODS: We tested serial serum samples from patients with PBC at a research institution for several autoantibodies. Long-term clinical follow-up data were used to calculate the slopes (change over time) for autoantibodies, platelet count, Ishak fibrosis score, biopsy copper, and number of portal areas with bile ducts. An adverse clinical outcome was defined as hepatic decompensation, development of hepatocellular carcinoma, liver transplantation, or liver-related death. We performed linear or logistic regression or Fisher exact test as appropriate, adjusting for multiple comparisons. RESULTS: Twenty-seven patients with PBC with 145 serum samples were studied. Of the cohort, 85% was white, 81% was female, and median follow-up time was 20 years. Of the autoantibodies tested, only sp100 changed significantly over time. The sp100 slope was inversely associated with the Ishak fibrosis slope (parameter estimate, -0.05; P = .0003). CONCLUSIONS: While changes in most autoantibodies over time do not seem to correlate with clinical outcomes in PBC, a change in the sp100 autoantibody level may have prognostic utility with respect to the development of fibrosis on liver biopsy.

Diagnostic and clinical significance of Crohn's disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA.

BACKGROUND: We developed a new IgA and IgG anti-MZGP2 antibody ELISAs based on recombinant isoform-4 of human zymogen granule protein-2 (GP2), which is the major autoantigen of Crohn's disease (CrD)-specific pancreatic autoantibodies and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date. METHODS: 832 sera were studied, including 617 consecutive IBD patients from 323 CrD and 294 ulcerative colitis (UC) follow-up in a tertiary centre, and 112 pathological and 103 normal controls. RESULTS: Sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 were 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and a specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75% (70, 80) and a specificity of 84% (79, 89). IgA anti-MZGP2 antibodies were more prevalent in CrD patients with early disease onset (p=0.011). Also, anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement. Patients with longer disease duration were more likely to have IgG anti-MZGP2 antibodies. CONCLUSIONS: Our novel ELISA confirms the high specificity of anti-MZGP2 antibodies for CrD and their association with disease severity phenotypes.

Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping.

BACKGROUND: Prevalence estimates for celiac disease (CD) depend on the method used. The role of deamidated gliadin peptide (DGP) and genetic testing in epidemiological studies and diagnostic settings of celiac disease (CD) has still to be established. OBJECTIVES: The objective of this article is to assess the prevalence of CD in Latvia by combining serological tests with DQ2.5/DQ8 testing. METHODS: A total of 1444 adults from a randomly selected cross-sectional general population sample were tested by ELISA for tTG IgA, DGP IgA and IgG antibodies (QUANTA Lite®, Inova Diagnostics Inc). Samples with tTG IgA ≥20U were tested for EMA IgA by indirect immunofluorescence assay, and all specimens with tTG IgA ≥15U were tested by QUANTA-Flash® chemiluminescent assays (CIA) (Inova Diagnostics Inc) for tTG IgA, DGP IgA and IgG. DQ2.5/8 was detected in individuals with any positive ELISA test and a subgroup of controls. RESULTS: Forty-three individuals (2.98%; 95% CI: 2.10-3.86%) tested positive by at least one ELISA test; 41.86% of the serology-positive individuals (any test above the cutoff) were DQ positive. Six individuals (0.42%; 95% CI: 0.09-0.75%) were triple ELISA positive, and DQ2.5 or DQ8 was positive in all; 0.35% (95% CI: 0.05-0.65%) were tTG IgA and EMA positive. Two tTG IgA-negative cases were both DGP IgG and IgA positive, both being DQ positive; including them in the "serology-positive" group would increase the prevalence to 0.49% (95% CI: 0.13-0.85%). CIA tests revealed 2 tTG IgA-positive and EMA-negative cases with a positive genotype. DQ2.5 or DQ8 genotype was positive in 28.6% of the serology-negative population. CONCLUSIONS: Estimates of the prevalence of CD in Latvia based on the serogenetic testing approach range from 0.35% to 0.49% depending on the criteria used. There is a rationale for combining serological tests and DQ2.5/8 genotyping.