[Influence of underlying disease and immunosuppression on the immunocompetence in inflammatory rheumatic diseases]. / Einfluss von Grunderkrankung und Immunsuppression auf die Immunkompetenz bei entzündlich rheumatischen Erkrankungen.

Patients with inflammatory rheumatic diseases have a higher risk of infections in comparison to the general population. For this patient group, in addition to cardiovascular diseases, infections play an important role with respect to morbidity and mortality. Even if it is difficult to make concrete statements with respect to individual diseases, it can be assumed that there is a lower risk of infections in inflammatory joint diseases in comparison to connective tissue diseases and vasculitides. The increased risk of infections is determined by multiple factors, whereby the underlying factors are classified into three main categories: patient-related factors (age, comorbidities, lifestyle), disease-related factors (immunological dysfunction as part of the disease pathophysiology) and drug-related factors (type and dosage of the immunosuppression and/or immunomodulation). An improved understanding of the complexity of these associations enables the optimization of treatment and disease control taking the individual risk factors into account, with the aim of a significant reduction in the risk of infections.

Induction of cross-reactive, mucosal anti-SARS-CoV-2 antibody responses in rheumatoid arthritis patients after 3rd dose of COVID-19 vaccination.

Systemic vaccination against SARS-CoV-2 elicited high titers of specific antibodies in the blood and in the oral cavity. Preexisting autoimmune diseases, such as rheumatoid arthritis, and biological treatments, like B cell depletion, are known to exhibit higher risk of severe COVID-19 manifestation and increased frequency of breakthrough infections after vaccination. We hypothesized that such increased risk is associated with an aberrant induction of secreted antibodies in the oral cavity. Here we evaluated the levels of secreted antibodies in the oral cavity against the SARS-CoV-2 Spike protein during the course of vaccination in RA patients with or without B cell depletion. We found that total salivary IgG levels were correlated with number of B cells in the blood. Anti-Spike IgG responses 7 days after second vaccination were induced in the oral cavity of all healthy individuals, while only 6 out 23 RA patients exhibited anti-Spike IgG in their saliva regardless of B cell depleting therapy. Importantly, both salivary and serologic anti-Spike IgG and IgA responses towards WT and omicron Spike variants were efficiently induced by third vaccination in RA patients with or without B cell depletion to the levels that were similar to healthy individuals. Altogether, these data advocate for the necessity of three dose vaccination for RA patients to mount anti-Spike antibody responses at the mucosal surfaces and annotate the reduction of secreted salivary IgG by B cell depletion.

[Janus kinase inhibitors : State of the art in clinical use and future perspectives]. / Januskinase-Inhibitoren : State of the Art im klinischen Einsatz und Zukunftsperspektiven.

BACKGROUND: Cytokines and associated intracellular signal cascades play a major role in the pathogenesis of autoimmune diseases. Janus kinases (JAK) are part of these intracellular signal transduction processes. A relatively new drug group of targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) are JAK inhibitors (JAKi) and are a promising treatment approach for autoimmune diseases. EFFICACY: Hitherto, three JAKis, Tofacitinib, Baricitinib and Upadacitinib, have been approved for treatment of Rheumatoid Arthritis (RA) in the USA, Switzerland and the EU. Filgotinib, another JAKi, also showed promising results in the treatment of RA. Furthermore, tofacitinib received approval for the treatment of ulcerative colitis and psoriatic arthritis. In addition to the JAKis already mentioned, several other JAKis, e.g. filgotinib and peficitinib, are being and were investigated in various studies on indications, such as atopic dermatitis, ankylosing spondylitis and systemic lupus erythematosus. SAFETY: Being immunosuppressants, JAKis show an elevated incidence of severe infections, comparable to biologics. The increased reactivation of varicella zoster virus is especially noteworthy. Under JAKi treatment cytopenia is also more frequent. Lymphopenia under JAKi treatment is of particular clinical relevance because of its association with an increase in the number of severe infections. Furthermore, an elevated risk of thromboembolic events, particularly pulmonary embolism has been noted. The risks concerning metabolic alterations and the occurrence of malignant neoplasms are comparable to those under treatment with biologics.