Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

Memory B cells and memory T cells induced by SARS-CoV-2 booster vaccination or infection show different dynamics and efficacy to the Omicron variant.

Although BNT162b2 vaccination was shown to prevent infection and reduce COVID-19 severity, and the persistence of immunological memory generated by the vaccination has not been well elucidated. We evaluated memory B and T cell responses to the SARS-CoV-2 spike protein before and after the third BNT162b2 booster. Although the antibody titer against the spike receptor-binding domain (RBD) decreased significantly 8 months after the second vaccination, the number of memory B cells continued to increase, while the number of memory T cells decreased slowly. Memory B and T cells from unvaccinated infected patients showed similar kinetics. After the third vaccination, the antibody titer increased to the level of the second vaccination, and memory B cells increased at significantly higher levels before the booster, while memory T cells recovered close to the second vaccination levels. In memory T cells, the frequency of CXCR5+CXCR3+CCR6- cTfh1 was positively correlated with RBD-specific antibody-secreting B cells. Furthermore, T cell-dependent antibody production from reactivated memory B cells in vitro was correlated to the Tfh-like cytokine levels. For the response to variant RBDs, although 60%-80% of memory B cells could bind to the Omicron RBD, their binding affinity was low, while memory T cells show an equal response to the Omicron spike. Thus, the persistent presence of memory B and T cells will quickly upregulate antibody production and T cell responses after Omicron strain infection, which prevents severe illness and death due to COVID-19.

Anti-SARS-CoV-2 cellular immunity in 571 vaccinees assessed using an interferon-γ release assay

Generation of antigen-specific memory T cells has been analyzed only for few coronavirus disease 2019 (COVID-19) vaccinees, whereas antibody titers have been serologically measured for a large number of individuals. Here, we assessed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular immune response in a large cohort using interferon (IFN)-{gamma} release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals who received the viral spike (S) protein-expressing BNT162b2 mRNA SARS-CoV-2 vaccine. Serum IgG titers against the receptor-binding domain (RBD) of S protein were measured. Samples of 28 vaccinees were subjected to flow cytometry analysis of T cells derived from short-term whole blood culture. IFN-{gamma} production triggered by S antigens was observed in most individuals 8 weeks after receiving the second dose of the vaccine, indicating acquisition of T cell memory responses. The frequencies of activated T cell subsets were strongly correlated with IFN-{gamma} levels, supporting the usability of our approach. S antigen-stimulated IFN-{gamma} levels were weakly correlated with anti-RBD IgG titers and associated with pre-vaccination infection and adverse reactions after the second dose. Our approach revealed cellular immunity acquired after COVID-19 vaccination, providing insights regarding the effects and adverse reactions of vaccination.