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Background Assessing serological inflammation is difficult in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients, as standard inflammation parameters, like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are influenced by interleukin-6-receptor inhibition. Calprotectin in the serum, also named S100A8/S100A9, might be a more useful inflammation parameter in TCZ-treated patients. Methods Sixty-nine RA patients taking TCZ were included. Serum-calprotectin levels were assessed, as well as ESR, CRP, need for a change in disease-modifying anti-rheumatic drugs due to RA activity (= active RA), and the RA clinical disease activity score (CDAI). Forty-five RA patients taking tumor-necrosis factor-inhibitors (TNFi) were investigated for the same parameters. Results TCZ-treated patients with active RA had higher calprotectin values than not active RA patients (4155.5 [inter quartile range 1865.3–6068.3] vs 1040.0 [676.0–1638.0] ng/ml, P < 0.001). A calprotectin cut-off value of 1916.5 ng/ml resulted in a sensitivity and specificity of 80.0 %, respectively, for the detection of RA disease activity. Calprotectin values correlated with CDAI-scores ( r = 0.228; P = 0.011). ESR and CRP were less suitable to detect RA activity in TCZ-treated patients. Also TNFi-treated patients with active RA had higher calprotectin values compared to not active RA (5422.0 [3749.0–8150.8] vs 1845.0 [832.0–2569.0] ng/ml, P < 0.001). The calprotectin value with the best sensitivity and specificity for detecting RA activity was 3690.5 ng/ml among TNFi-treated patients. Conclusion Calprotectin in the serum can be a useful inflammation parameter despite TCZ-treatment.

The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14 and May 28 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.

Background Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine production of B cells in patients with SSc after aHSCT. Methods Peripheral blood of six patients with SSc was collected at defined intervals up to 16 months after aHSCT. Immunophenotyping was performed, and B cell function was determined by measuring cytokine secretion in supernatants of stimulated B cell cultures. Results Within 1 month after aHSCT, a peak in the percentage of CD38 ++ /CD10 + /IgD + transitional B cells and CD38 ++ /CD27 ++ /IgD − plasmablasts was detected. Long-term changes persisted up to 14 months after aHSCT and showed an increased percentage of total B cells; the absolute B cell number did not change significantly. Within the B cell compartment, an increased CD27/IgD + naïve B cell percentage was found whereas decreased percentages of CD27 + /IgD + pre-switched memory, CD27 + /IgD − post-switched memory, and CD27 − /IgD − double-negative B cells were seen after aHSCT. Cytokine secretion in B cell cultures showed significantly increased IL-10 concentrations 13 to 16 months after aHSCT. Conclusion A changed composition of the B cell compartment is present for up to 14 months after aHSCT indicating positive persisting effects of aHSCT on B cell homeostasis. The cytokine secretion profile of B cells changes in the long term and shows an increased production of the immune regulatory cytokine IL-10 after aHSCT. These findings might promote the clinical improvements after aHSCT in SSc patients.

We present the case of a 22-year-old male who was first diagnosed with chronic recurrent multifocal osteomyelitis (CRMO) at the age of 16 years. During treatment with the tumor necrosis factor (TNF)-alpha inhibitor adalimumab, he developed severe palmoplantar psoriasis that affected his quality of life and necessitated discontinuation of the drug despite its efficacy against CRMO. Subsequent treatment with the interleukin (IL)-17a inhibitor secukinumab did not improve the psoriasis and led to a recurrence of the osteomyelitis. Therefore, the TYK-2 inhibitor deucravacitinib, approved in 2023 for the treatment of moderate to severe plaque psoriasis, was initiated. This resulted in clinical and morphological complete and sustained remission of CRMO within 12 weeks and a significant improvement of the psoriasis after six months of treatment with no occurrence of severe adverse events. To our knowledge, this is the first case report demonstrating complete and safe remission of CRMO associated with palmoplantar psoriasis treated with the TYK2 inhibitor deucravacitinib.

Background Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations. Methods A prospective long-term follow up study was performed including patients with rheumatic diseases and clonal T cell populations. Clinical features, adverse events, especially infections and cytopenias, and immunosuppressive medication were assessed. T cell populations were characterized by polymerase chain reaction, flow cytometry and stimulated cell cultures. Results 28 Patients with rheumatoid arthritis, spondyloarthritis, or giant cell arteritis were prospectively followed for up to 7.6 years. Severe infections or cytopenias (10.7% autoimmune neutropenias) were rare. The clonal T cell populations mostly persisted over time, the tumor burden decreased in the long-term. The cytokine secretion in stimulated T cell cultures did not differ in the subgroup of RA patients with versus without clonal T cells. Conclusion Clonal T cell populations in patients with rheumatic diseases are common, but are rarely harmful. Feared neutropenia, infections or progression into T cell leukemia could not be detected in the long-term in our cohort.

BackgroundThe complex nature of rheumatic diseases poses considerable challenges for clinicians when developing individualized treatment plans. Large language models (LLMs) such as ChatGPT could enable treatment decision support.ObjectiveTo compare treatment plans generated by ChatGPT-3.5 and GPT-4 to those of a clinical rheumatology board (RB).Design/methodsFictional patient vignettes were created and GPT-3.5, GPT-4, and the RB were queried to provide respective first- and second-line treatment plans with underlying justifications. Four rheumatologists from different centers, blinded to the origin of treatment plans, selected the overall preferred treatment concept and assessed treatment plans’ safety, EULAR guideline adherence, medical adequacy, overall quality, justification of the treatment plans and their completeness as well as patient vignette difficulty using a 5-point Likert scale.Results20 fictional vignettes covering various rheumatic diseases and varying difficulty levels were assembled and a total of 160 ratings were assessed. In 68.8% (110/160) of cases, raters preferred the RB’s treatment plans over those generated by GPT-4 (16.3%; 26/160) and GPT-3.5 (15.0%; 24/160). GPT-4’s plans were chosen more frequently for first-line treatments compared to GPT-3.5. No significant safety differences were observed between RB and GPT-4’s first-line treatment plans. Rheumatologists’ plans received significantly higher ratings in guideline adherence, medical appropriateness, completeness and overall quality. Ratings did not correlate with the vignette difficulty. LLM-generated plans were notably longer and more detailed.ConclusionGPT-4 and GPT-3.5 generated safe, high-quality treatment plans for rheumatic diseases, demonstrating promise in clinical decision support. Future research should investigate detailed standardized prompts and the impact of LLM usage on clinical decisions.

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment option in patients with severe forms of systemic sclerosis (SSc) by resetting the immune system. Nevertheless, secondary autoimmune disorders and progressive disease after aHSCT might necessitate renewed immunosuppressive treatments. This is particularly challenging when organ dysfunction, i.e., end-stage kidney failure, is present. In this case report, we present the unique case of a 43-year-old female patient with rapidly progressive diffuse systemic sclerosis who underwent aHSCT despite end-stage renal failure as consequence of SSc-renal crisis. Therefore, conditioning chemotherapy was performed with melphalan instead of cyclophosphamide with no occurrence of severe adverse events during the aplastic period and thereafter. After aHSCT, early disease progression of the skin occurred and was successfully treated with secukinumab. Thereby, to the best of our knowledge, we report the first case of successful aHSCT in a SSc-patient with end-stage kidney failure and also the first successful use of an IL-17 inhibitor to treat early disease progression after aHSCT.

•RA patients showed lower IgG-anti-TBEV compared to HC.•In RA, IgG-anti-TBEV are influenced by age at, time since last TBEV vaccination and disease duration.•Higher IgG-anti-TBEV responses in RA patients who had received booster vaccination.•Lower natural killer cell responses in RA patients.•Immunological benefits are suggested for timely boosters. Inactivated vaccines, such as tick-borne-encephalitis-virus-(TBEV) vaccine, have been discussed as less immunogenic in elderly and in immunocompromised patients. In this controlled cross-sectional cohort study, the antibody and cellular responses after TBEV-vaccination were investigated in 36 rheumatoid arthritis (RA) patients and 112 healthy controls (HC) by evaluating IgG-anti-TBEV concentration, neutralization and relative avidity index (RAI). Cellular reactivity was assessed by IFNgamma-producing spot-forming-units (SFU) by ELISPOT assay and flow cytometry. RA patients showed lower IgG-anti-TBEV compared to HC, which were influenced by age at and time since last TBEV vaccination and disease duration. High-responders regarding cellular immunity and avidity were less frequent in RA compared to HC. RA patients who had received booster vaccinations were more likely to demonstrate higher IgG-anti-TBEV responses compared to those who had not. In conclusion, RA patients showed a negative effect of age on anti-TBEV-IgG and immunological benefits of timely booster vaccination are suggested.

Background Autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for a selected group of systemic sclerosis (SSc) patients with good available evidence but can be associated with considerable morbidity and mortality. The aim of this study was to describe infectious complications and distinct immune reconstitution patterns after aHSCT and to detect risk factors in lymphocyte subsets, which are associated with an elevated rate of infections after aHSCT. Methods Seventeen patients with SSc were included in this single-center retrospective cohort study. Clinical and laboratory data was collected before and for 12 months after aHSCT, including immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting. Results Cytomegalovirus (CMV) reactivations were common in CMV-IgG-positive patients (50%) and needed treatment. Mycotic infections occurred in 17.6%. One patient died (resulting in a mortality of 5.9%) due to pneumonia with consecutive sepsis. All patients showed decreased T helper cells (CD3 + /CD4 + ) and within the B cell compartment decreased post-switched memory B cells (CD19 + /CD27 + /IgD − ) and elevated naïve B cells (CD19 + /CD27 − /IgD + ) until 12 months after aHSCT. Patients who developed infections had significantly lower B cells before aHSCT than patients who did not develop infections. Conclusion After aHSCT, monitoring for infectious complications, especially for CMV reactivations, is crucial as the reconstitution of the immune system takes longer than 12 months. Low peripheral B cells might be a risk factor for an elevated infection rate.

To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease. In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation. In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age <60 years (OR = 1.78), RAID score >2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy. Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms. This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483).