Objective. To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = &), versus normal controls (n = 60). Methods. ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC).Results. T cells were the major source of interleukin-2 (IL-2), IL-4, and interferon-? (IFNy), whereas monocytes were the primary source of IL-6 and IL-10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFNy and IL-2 (P 5 0.03), while significantly more PBMC produced IL-6 and IL-10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL-lO:IFN.]csecreting cells (P < 0.001).Conclusion. SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine-secreting PBMC.Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by multiple immune abnormalities that culminate in the overproduction of pathogenic autoantibodies (1-4). T cells and the factors they produce have been implicated in the development of lupus in mice and humans (5-7).Two broad classes of cytokines have been identified. Interferon-y (IFN y) and interleukin-2 (IL-2)

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

Budesonide may be of value in the management of refractory celiac disease.

C urrently, 3 vaccines have been granted Emergency Use Authorization for coronavirus disease 2019 prevention in the United States. These include the messenger RNA (mRNA) platform vaccines (mRNA-1273; Moderna/National Institutes of Health) and BNT162b2 (Pfizer-BioNTech) and an adenovirus vector vaccine (Ad26.CoV2.S; Johnson & Johnson), which were 94%, 95%, and 67% effective against COVID-19 infection in their phase III registry trials against the endemic variants at the time, respectively. 1-3 All 3 vaccines target the viral spike (S) protein that facilitates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into host cells via its receptor binding domain, which interacts with angiotensin-converting enzyme 2. 4 Although the mRNA platform vaccines are 2-dose vaccines administered 3-4 weeks apart, the Ad26.CoV2.S is administered as a single dose. Another adenovirus vector vaccine (ChAdOx1; Astrazeneca), not yet authorized in the United States, is intended as a 2-dose regimen with an interval of 8-12 weeks.Patients with inflammatory bowel disease (IBD) on corticosteroids, immunomodulators, and advanced therapies may have normal to slightly decreased humoral responses to the SARS-CoV-2 mRNA vaccine platforms. 1 In addition, patients receiving infliximab and/or thiopurines have significantly lower rates of seroconversion than those on vedolizumab monotherapy after a single dose of either BNT162b2 or ChAdOx1. 2 A study of solid organ transplant recipients showed decreased humoral responses to Ad26.CoV2.S vaccine relative to both mRNA platform vaccines, although it is unknown whether these findings are generalizable to other immune compromised populations. 5 Q5 We aimed to assess for differences in serologic responses among patients with IBD who received Ad26.CoV2.S relative to those receiving mRNA-1273 or BNT162b2. Among 353 vaccine recipients with IBD participating in a prospective SARS-CoV-2 vaccine registry without prior COVID-19 infection and who had completed a full vaccine regimen, 148 (42%), 193 (55%), and 12 (3%) received mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively. Demographic and disease characteristics were similar across vaccine groups (mean age, 51 years, 62% were female) (Supplementary Table 1). Approximately 290 (83.1%) participants were on immune-modifying therapies (IMTs), as defined by receipt of advanced therapies (biologics or JAK inhibitors, 80.2%), immunomodulators (16.6%), and/or systemic corticosteroids (6.6%) at the time of initial vaccination. At least 2 weeks after completion of the vaccine regimen, positive antibody levels were detected in 121 (100%), 142 (99%), and 9 (90%) patients receiving mRNA-1273, BNT162b2, and Ad26.CoV2.S, respectively (Figure 1A). Quantitative log 10 (anti-Spike IgG

Background The safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown. Methods We compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD. Results The study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse. Conclusion The frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.