Impact of COVID-19 infection and vaccination in pancreatobiliary IgG4-related disease patients: An international multicenter study.

BACKGROUND AND AIM: Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown. METHODS: Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort. RESULTS: Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed. CONCLUSION: While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

IgG4-related Disease Emerging after COVID-19 mRNA Vaccination.

A 78-year-old Japanese woman with no history of rheumatic disease received 2 doses of the BNT162b2 COVID-19 mRNA vaccine. Two weeks later, she noticed bilateral swelling in the submandibular region. Blood tests showed hyper-immunoglobulin (Ig)G4emia, and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) revealed the strong accumulation of FDG in the enlarged pancreas. She was diagnosed with IgG4-related disease (IgG4-RD) according to the American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria. Treatment was started with prednisolone at 30 mg/day, and the organ enlargement improved. We herein report a case of IgG4-RD that may have been associated with an mRNA vaccine.

IgG4-Related Disease: A Constellation of Abdominal Manifestations.

IgG4-related disease is an autoimmune condition that results in inflammation and fibrosis throughout multiple organ systems. This disease is rare; however, it can mimic many more prevalent conditions clinically and thus should be included in their differential diagnoses. Although autoimmune pancreatitis is the most common abdominal manifestation, the disease can afflict the hepatobiliary, vascular and renal systems as well. We present a case of a 78-year-old male with symptoms of chronic fatigue and weight loss. Imaging was performed with the expectation of revealing a malignancy, although the features of IgG4-related disease involving multiple organs were detected instead. Serology confirmed the diagnosis. It is imperative to diagnose IgG4-related disease early as it has a different treatment and favorable prognosis compared to many malignancies.

Case Report: Severe Complement-Mediated Thrombotic Microangiopathy in IgG4-Related Disease Secondary to Anti-Factor H IgG4 Autoantibodies.

Objective: To first describe and estimate the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy (TMA) in a patient with IgG4-related disease (IgG4-RD). Methods: This study is a case report presenting a retrospective review of the patient's medical chart. Plasma complement C3 and C4 levels, immunoglobulin isotypes and subclasses were determined by nephelometry, the complement pathways' activity (CH50, AP50, MBL) using WIESLAB® Complement System assays. Human complement factor H levels, anti-complement factor H auto-antibodies were analyzed by ELISA, using HRP-labeled secondary antibodies specific for human IgG, IgG4, and IgA, respectively. Genetic analyses were performed by exome sequencing of 14 gens implicated in complement disorders, as well as multiplex ligation-dependent probe amplification looking specifically for CFH, CFHR1-2-3, and 5. Results: Our brief report presents the first case of IgG4-RD with complement-mediated TMA originating from both pathogenic CFHR 1 and CFHR 4 genes deletions, and inhibitory anti-complement factor H autoantibodies of the IgG4 subclass. Remission was achieved with plasmaphereses, corticosteroids, and cyclophosphamide. Following remission, the patient was diagnosed with lymphocytic meningitis and SARS-CoV-2 pneumonia with an uneventful recovery. Conclusion: IgG4-RD can be associated with pathogenic IgG4 autoantibodies. Genetic predisposition such as CFHR1 and CFHR4 gene deletions enhance the susceptibility to the formation of inhibitory anti-Factor H IgG4 antibodies.