SARS‐CoV‐2 vaccination response in patients with autoimmune hepatitis and autoimmune cholestatic liver disease

Abstract

Background/Aims: In this observational study, we explored the humoral and cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune hepatitis (AIH) and patients with cholestatic autoimmune liver disease (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]). Methods: Anti-SARS-CoV-2 antibody titers were determined using the DiaSorin LIAISON and Roche immunoassays in 103 AIH, 64 PSC, and 61 PBC patients and 95 healthy controls >14 days after the second COVID-19 vaccination. The spikespecific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of individuals.Results: Previous SARS-CoV-2 infection was frequently detected in AIH but not in PBC/PSC (10/112 (9%), versus 4/144 (2.7%), p = 0.03). In the remaining patients, seroconversion was measurable in 97% of AIH and 99% of PBC/PSC patients, respectively. However, in 13/94 AIH patients antibody levels were lower than in any healthy control, which contributed to lower antibody levels of the total AIH cohort when compared to PBC/PSC or controls (641 vs. 1020 vs. 1200 BAU/ml, respectively). Notably, antibody levels were comparably low in AIH patients with (n = 85) and without immunosuppression (n = 9). Also, antibody titers significantly declined within 7 months after the second vaccination. In the AIM assay of 20 AIH patients, a spike-specific T-cell response was undetectable in 45% despite a positive serology, while 87% (13/15) of the PBC/PSC demonstrated a spike-specific T-cell response.Paul Duengelhoef, Johannes Hartl and Darius Rüther shared co-first author ship.

COVID-19 and liver disease

“…In the general population, the antibody response after two doses of the anti-SARS-CoV-2 mRNA Pfizer-BioNTech BNT162b2 and Moderna−1273 vaccines is excellent147 148; however, it is unsatisfactory in patients with LT and with CLD,146 149 150 with the exception of NAFLD 151. In case of AIH, the response to SARS-CoV-2 vaccine appears to be impaired in comparison to PBC and PSC even in the absence of immunosuppression 152…”

High‐resolution analysis of individual spike peptide‐specific CD4+ T‐cell responses in vaccine recipients and COVID‐19 patients

“…Using a selection of frequently detected spike‐specific peptides as specific stimulation (Supplementary table 2 ), we performed an activation‐induced marker (AIM) T‐cell assay similar to previously described protocols to compare the ex vivo magnitude and phenotype of the virus‐specific CD4 + T‐cell response. 54 , 55 , 56 , 57 AIM assays are believed to have a higher sensitivity than ICS, which is thought to underestimate the actual frequency of antigen‐specific T cells. 58 Here, antigen‐reactive CD4 + T cells were identified by the co‐expression of CD137 (4–1BB) and CD154 (CD40L), while antigen‐reactive CD8 + T cells were defined as CD69 + CD137 + (Figure 5a and Supplementary figure 12a ).…”

“…Using a selection of frequently detected spike‐specific peptides as specific stimulation (Supplementary table 2), we performed an activation‐induced marker (AIM) T‐cell assay similar to previously described protocols to compare the ex vivo magnitude and phenotype of the virus‐specific CD4 + T‐cell response 54–57 . AIM assays are believed to have a higher sensitivity than ICS, which is thought to underestimate the actual frequency of antigen‐specific T cells 58 .…”

“…The AIM assay was performed as previously described 54 , 55 , 56 , 57 with a few adaptations. In short, cryopreserved PBMCs were stimulated for 18 h with the pool of 11 frequently recognised peptides (Supplementary table 2 ) or staphylococcal enterotoxin B (SEB) (Sigma‐Aldrich) or were left untreated.…”

COVID-19 and Autoimmune Liver Diseases

“…This study demonstrated that 89% of patients seroconverted within four weeks post second dose whereas 11% of patients failed to reach seroconversion. A prospective observational study comparing the humoral and T-cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune liver disease has been recently published [ 43 ]. One hundred and three patients with AIH and 125 patients with PBC or PSC were included.…”