Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases.

BACKGROUND: Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases. METHODS: In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases. RESULTS: Glycan traits bisection (OR: 3.78 [1.88-9.35], p-value: 5.88 × 10- 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75-5.16], p-value: 1.63 × 10- 3), IgG1 galactosylation (OR: 0.35 [0.2-0.58], p-value: 3.47 × 10- 5) and hybrid type glycans (OR: 2.73 [1.67-4.89], p-value: 2.31 × 10- 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity. CONCLUSIONS: Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.

Circulating Levels of Anti-C1q and Anti-Factor H Autoantibodies and Their Targets in Normal Pregnancy and Preeclampsia.

Preeclampsia (PE) generally manifests in the second half of pregnancy with hypertension and proteinuria. The understanding of the origin and mechanism behind PE is incomplete, although there is clearly an immune component to this disorder. The placenta constitutes a complicated immune interface between fetal and maternal cells, where regulation and tolerance are key. Stress factors from placental dysfunction in PE are released to the maternal circulation evoking the maternal response. Several complement factors play a role within this intricate landscape, including C1q in vascular remodeling and Factor H (FH) as the key regulator of alternative pathway complement activation. We hypothesize that decreased levels of C1q or FH, or disturbance of their function by autoantibodies, may be associated with PE. Autoantibodies against C1q and FH and the concentrations of C1q and FH were measured by ELISA in maternal sera from women with preeclamptic and normal pregnancies. Samples originated from cohorts collected in the Netherlands (n=63 PE; n=174 control pregnancies, n=51 nonpregnant), Finland (n=181 PE; n=63 control pregnancies) and Norway (n=59 PE; n=27 control pregnancies). Serum C1q and FH concentrations were higher in control pregnancy than in nonpregnant women. No significant differences were observed for serum C1q between preeclamptic and control pregnancy in any of the three cohorts. Serum levels of FH were lower in preeclamptic pregnancies compared to control pregnancies in two of the cohorts, this effect was driven by the early onset PE cases. Neither anti-C1q autoantibodies nor anti-FH autoantibodies levels differed between women with PE and normal pregnancies. In conclusion, levels of anti-C1q and anti-FH autoantibodies are not increased in PE. C1q and FH are increased in pregnancy, but importantly, a decrease in FH concentration is associated with PE.

Presence of Autoantibodies in Erosive Hand Osteoarthritis and Association with Clinical Presentation.

OBJECTIVE: To investigate whether 3 rheumatoid arthritis-associated antibodies [rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) or anticarbamylated protein (anti-CarP) antibodies] are present in hand osteoarthritis (HOA) and associate with erosive OA (EOA). METHODS: Anti-CarP IgG was measured by ELISA in baseline sera of patients with HOA from 3 cohorts: HOSTAS (n = 510, 27.2% EOA), ECHO (n = 47), and EHOA (n = 23), and in sera of healthy controls (HC; n = 196, mean age 44.1 yrs, 51.0% women). Moreover, ACPA-IgG and RF-IgM were additionally determined in HOSTAS and HC. The prevalence of autoantibodies was compared between HOA and HC and between erosive and nonerosive HOA. In HOSTAS, hand radiographs were scored (Kellgren-Lawrence, Osteoarthritis Research Society International osteophyte and joint space narrowing) and C-reactive protein (CRP) levels, representing inflammation, were assessed. Groups were compared using nonparametric tests. RESULTS: The prevalence of anti-CarP was low and not significantly different between the total HOA group and HC (6.6% vs 3.6%, p = 0.12). In HOSTAS, the prevalence of all tested autoantibodies was low (anti-CarP 7.1%, ACPA 0.8%, RF 6.1%), and there were no significant differences observed between HOA patients and HC or between erosive and nonerosive HOA. Further, radiographic damage and CRP levels were similar in anti-CarP+ and anti-CarP-, and RF+ and RF- HOSTAS patients. CONCLUSION: The prevalence of autoantibodies is similar in HOA patients and HC, and these autoantibodies are not associated with erosive disease, structural damage, or inflammation in patients with HOA, indicating that another mechanism is driving erosive disease.