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Little is known about the mechanisms triggering and controlling both the development and perpetuation of extraintestinal complications in CD. The aim of the present study was to test the hypothesis that the T cell immune response in CD patients with joint complications may be altered when compared with patients without extraintestinal manifestations. We used a semiquantitative polymerase chain reaction assay to analyse the T cell antigen receptor repertoire in peripheral blood T cells from eight CD patients suffering from peripheral arthritis and ankylosing spondylitis, 12 CD patients without extraintestinal manifestations, and from seven non-CD patients with ankylosing spondylitis showing typical changes on joint radiographs. Being concerned that different patterns may be seen in different phases of the inflammatory disease process, we have also taken care lo analyse sequential samples at various time points of the disease. Expression of all 22 Vβ genes was found in each healthy control and in each CD patient without extraintestinal manifestations and showed no major variation over time. Southern hybridization analysis of amplified products revealed a highly restricted Vβ repertoire in all CD patients suffering from peripheral arthritis and ankylosing spondylitis. In contrast, non-CD patients with ankylosing spondylitis without signs or symptoms of gastrointestinal problems demonstrated the presence of the entire Vβ repertoire. Our longitudinal studies confirmed variable Vβ usage over time, as certain transcripts were found only in distinct temporal phases of disease. Our data are not directly suggestive of a common superantigen model of CD, but instead emphasize a specific decrease in signals throughout the T cell receptor Vβ repertoire in CD patients suffering from joint complications. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect., Methods: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10 6 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10 6 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed., Results: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10 6 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment., Conclusion: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients., (© 2023. The Author(s).)

Little is known about the mechanisms triggering and controlling both the development and perpetuation of extraintestinal complications in CD. The aim of the present study was to test the hypothesis that the T cell immune response in CD patients with joint complications may be altered when compared with patients without extraintestinal manifestations. We used a semiquantitative polymerase chain reaction assay to analyse the T cell antigen receptor repertoire in peripheral blood T cells from eight CD patients suffering from peripheral arthritis and ankylosing spondylitis, 12 CD patients without extraintestinal manifestations, and from seven non-CD patients with ankylosing spondylitis showing typical changes on joint radiographs. Being concerned that different patterns may be seen in different phases of the inflammatory disease process, we have also taken care to analyse sequential samples at various time points of the disease. Expression of all 22 V beta genes was found in each healthy control and in each CD patient without extraintestinal manifestations and showed no major variation over time. Southern hybridization analysis of amplified products revealed a highly restricted V beta repertoire in all CD patients suffering from peripheral arthritis and ankylosing spondylitis. In contrast, non-CD patients with ankylosing spondylitis without signs or symptoms of gastrointestinal problems demonstrated the presence of the entire V beta repertoire. Our longitudinal studies confirmed variable V beta usage over time, as certain transcripts were found only in distinct temporal phases of disease. Our data are not directly suggestive of a common superantigen model of CD, but instead emphasize a specific decrease in signals throughout the T cell receptor V beta repertoire in CD patients suffering from joint complications.