Altered cellular immune response to vaccination against SARS-CoV-2 in patients suffering from autoimmunity with B-cell depleting therapy.

B-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytometry. Anti-SARS-CoV-2 spike receptor-binding domain antibody assays were performed to elucidate B-cell responses. To complement our cellular analysis, we performed immunophenotyping for T- and B-cell subsets. We show that SARS-CoV-2 vaccination using mRNA vaccines elicits cellular T-cell responses in patients under B-cell depleting therapy. Some facets of this immune response including TNFα production of CD4+ T-cells and granzyme B production of CD8+ T-cells, however, are distinctly diminished in these patients. Consequently, it appears that the finely coordinated process of T-cell activation with a uniform involvement of CD4+ and CD8+ T-cells as seen in HCs is disturbed in autoimmune patients. In addition, we observed that immune cell composition does impact cellular immunity as well as sustainability of anti-spike antibody titers. Our data suggest disturbed cellular immunity following mRNA vaccination in patients treated with B-cell depleting therapy. Immune cell composition may be an important determinant for vaccination efficacy.

Association of immunological parameters with aortic dilatation in giant cell arteritis: a cross-sectional study.

Aortic dilatation (AD) occurs in up to 30% of patients with giant cell arteritis (GCA). Reliable biomarkers for AD development, however, are still absent. The aim of this exploratory study was to evaluate whether immunological parameters are associated with the occurrence of AD in GCA. Cross-sectional study on 20 GCA patients with AD, 20 GCA patients without AD, and 20 non-GCA controls without AD measuring leukocytes, neutrophils, lymphocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), interferon (IFN)-α, IFN-γ, IFN-γ-induced protein 10 (IP-10), interleukin (IL) 5, IL-8, IL-10, IL-17A, IL-18, IL-1 receptor antagonist, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF), L-selectin, P-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1). AD was measured by aortic contrast-enhanced computed tomography and defined by enlargement of the aorta above population-based aortic diameters adjusted by age, gender, and body surface area. No significant differences were observed between GCA patients with AD and GCA patients without AD concerning levels of leukocytes, neutrophils, lymphocytes, CRP, ESR, SAA, IL-8, IL-18, PDGF, IP-10, selectins, and sICAM-1. Values of IFN-α, IFN-γ, IL-5, IL-10, IL-17A, IL-1 receptor antagonist, and TNF-α were all below the detection limits in more than 70% of subjects. Lymphocytes and CRP revealed positive correlations with the diameter of the thoracic descending aorta. Immunological parameters were not useful to conclude on the presence of AD in GCA. Further studies are required to test if CRP and lymphocytes may be useful to predict future development of AD in GCA.

Sjögren syndrome: looking forward to the future.

Primary Sjögren's syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.

Patterns of Peripheral Blood B-Cell Subtypes Are Associated With Treatment Response in Patients Treated With Immune Checkpoint Inhibitors: A Prospective Longitudinal Pan-Cancer Study.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. Methods: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. Results: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21- B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). Conclusion: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types.

Membranous nephropathy associated with immunoglobulin G4-related disease successfully treated with obinutuzumab.

Immunoglobulin G4 (IgG4)-releated disease is typically associated with interstitial nephritis, but rare cases of idiopathic membranous nephropathy as a renal manifestation have been described. Obinutuzumab was successfully used in refractory membranous nephropathy, but evidence for the treatment of IgG4-related disease with obinutuzumab is lacking. We report one patient's case with membranous nephropathy associated with IgG4-related disease who was treated with obinutuzumab following an anaphylactic reaction to rituximab. Obinutuzumab treatment resulted in a sustained complete remission of membranous nephropathy and a decrease of IgG4 to the normal range. This case demonstrates that membranous nephropathy associated with IgG4-related disease can be treated successfully with obinutuzumab.

Ultrasound in osteoarthritis of the hand: a comparison to computed tomography and histology.

OBJECTIVE: To compare structural findings between US, micro-CT (µCT) and histology in people with OA of the hands. METHODS: We analysed DIP and PIP joints of 31 fingers from 15 dissecting-room cadavers with OA of the hands. The occurrence of bone erosions and osteophytes were recorded by US, µCT and histology at 16 regions for each joint and compared for each method. RESULTS: In total, US (n = 558, 56.2% of 992 examined regions) and µCT (n = 493, 49.7%) detected a higher frequency of osteophytes at PIP and DIP joints than histology (n = 161, 23.4% of 689 histological examined regions; P = 0.01). We found a comparable number of erosions with each method [US, n = 52 (5.2%); µCT, n = 43 (4.3%); histology, n = 35 (5.2%)]. Both imaging techniques correlated moderately with each other regarding the detection of osteophytes (r = 0.54, P = 0.002) and erosions (r = 0.43, P = 0.017). Neither US nor µCT correlated with histology regarding erosions or osteophytes. With histology as the reference, US had a sensitivity of 80% and a specificity of 32% to detect osteophytes, whereas µCT had a sensitivity of 73% and a specificity of 27%. For erosions, sensitivities (US 10% and µCT 6%, respectively) were much lower. Microscopically, erosions contained fibrous myxoid tissue extending from subcortical cavities through the breach of cortical bone. CONCLUSIONS: The ability of US to identify osteophytes was comparable to that of µCT, yielding a good sensitivity when histology was used as the gold standard. The sensitivity of US and µCT to detecting erosions was low compared with histology.

CD19+IgD+CD27- Naïve B Cells as Predictors of Humoral Response to COVID 19 mRNA Vaccination in Immunocompromised Patients.

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.

Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis.

Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology-and progression-of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.

T Cell Phenotyping in Individuals Hospitalized with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic. Cytokine release syndrome occurring in a minority of SARS-CoV-2 infections is associated with severe disease and high mortality. We profiled the composition, activation, and proliferation of T cells in 20 patients with severe or critical COVID-19 and 40 matched healthy controls by flow cytometry. Unsupervised hierarchical cluster analysis based on 18 T cell subsets resulted in separation of healthy controls and COVID-19 patients. Compared to healthy controls, patients suffering from severe and critical COVID-19 had increased frequencies of activated and proliferating CD38+Ki67+ CD4+ and CD8+ T cells, suggesting active antiviral T cell defense. Frequencies of CD38+Ki67+ Th1 and CD4+ cells correlated negatively with plasma IL-6. Thus, our data suggest that patients suffering from COVID-19 have a distinct T cell composition that is potentially modulated by IL-6.

Lymphopenia in primary Sjögren's syndrome is associated with premature aging of naïve CD4+ T cells.

OBJECTIVE: To investigate peripheral lymphopenia, a frequent finding in primary Sjögren's syndrome (pSS) associated with higher disease activity and increased mortality. METHODS: Prospective, cross-sectional study of consecutive patients with pSS (n = 66) and healthy controls (n = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated ß-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP). RESULTS: In pSS, lymphopenia mainly affected naïve CD4+ T cells. We noted a lower frequency of proliferating naïve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, naïve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of naïve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers. CONCLUSION: In pSS, evidence for increased proliferation of naïve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of naïve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS.

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study.

AIMS: Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear. METHODS: In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2ß, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios. RESULTS: In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively. CONCLUSION: In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.

Rheumatic Musculoskeletal Diseases and COVID-19 A Review of the First 6 Months of the Pandemic.

In December 2019, a cluster of severe pneumonia was observed in China, with the subsequent discovery of a new beta-coronavirus (SARS-CoV-2) as the causative agent. The elicited disease COVID-19 is characterized by fever, dry cough, myalgia, or fatigue and has a favorable outcome in the majority of cases. However, in some patients COVID-19 leads to severe pneumonia and sepsis with subsequent respiratory failure and gastrointestinal, hematological, neurological, and cardiovascular complications. A higher risk of infection is intrinsic to active rheumatic and musculoskeletal diseases (RMD) and the use of biological disease modifying anti-rheumatic drugs (DMARDs). With an increasing number of reports on COVID-19 in RMD patients, we are beginning to appraise their risks. In this review, we summarize the published cases of COVID-19 infections in RMD patients, including patients with inflammatory arthritis and connective tissue diseases as well as anti-phospholipid syndrome and Kawasaki syndrome. Overall, patients with inflammatory arthritis do not seem to be at a higher risk for infection or a severe course of COVID-19. Risk for critical COVID-19 in patients with systemic inflammatory diseases such as SLE or vasculitis might be increased, but this needs further confirmation. Furthermore, we summarize the data on DMARDs used to fight SARS-CoV-2 infection and hyperinflammation.

Case Report: Extensive Phosphorylation of Interleukin-1 Receptor-Associated Kinase 4 in a Patient With Schnitzler Syndrome.

Schnitzler syndrome (SchS) is a rare autoinflammatory disease, characterized by urticarial rash, recurrent fever, osteo-articular pain/arthritis with bone condensation, and monoclonal gammopathy. Diagnosis may be difficult due to overlapping signs with other diseases. Here, we describe the case of a 62-year-old man with SchS, who was initially misdiagnosed with multicentric Castleman disease (MCD). As excessive release of IL-6 is characteristic of MCD, in contrast to IL-1 in SchS, we measured the phosphorylation of intracellular signaling proteins of the respective pathways by flow cytometry. We found a distinct increase of phosphorylated IRAK-4 in our patient's B cells and monocytes while phosphorylation of STAT-3 was low, suggesting predominant IL-1 signaling. In accordance with these results and the classification criteria, we established the diagnosis of SchS instead of MCD and commenced therapy with the IL-1 receptor antagonist anakinra. We observed a rapid remission of signs accompanied by a reduction of phosphorylated IRAK-4 to normal levels. In conclusion, we propose phosphorylated IRAK-4 in B cells and monocytes as a potential marker for diagnosis of SchS and for treatment response to IL-1 blockade.

Effects of Probiotic Strains on Disease Activity and Enteric Permeability in Psoriatic Arthritis-A Pilot Open-Label Study.

(1) Background: Psoriatic Arthritis (PsA) is a painful disease of the joints and spine. Recent reports observed distinct enteric dysbiosis in PsA; intake of probiotic strains is considered to ameliorate enteric dysbiosis. If probiotics are effective in PsA is elusive. (2) Methods: In this pilot open-label study we enrolled 10 PsA patients with low to medium disease activity who received probiotics for 12 weeks. Analysis of faecal zonulin, α1-antitrypsin and calprotectin, as well as peripheral immune phenotyping was performed at baseline, after 12 weeks and 12 weeks after termination of probiotic intake. (3) Results: All patients showed increased levels of the enteric permeability marker zonulin which correlated with the frequency of peripheral Th17 cells. Calprotectin, a marker for intestinal inflammation was elevated in 6 out of 10 patients. Probiotic intake resulted in a reduction of disease activity and gut permeability. These effects, however, were not sustained beyond termination of probiotic intake. (4) Conclusions: PsA patients suffer from enhanced enteric permeability and inflammation. Probiotics may ameliorate disease activity in PsA by targeting these alterations.

Assessing health-related quality of life in primary Sjögren's syndrome-The PSS-QoL.

OBJECTIVES: To develop a questionnaire for the assessment of health-related quality of life (HRQL) in primary Sjögren's syndrome (PSS), and to test its psychometric properties. METHODS: Based on the concepts of a previous qualitative study, a questionnaire for the assessment of HRQL in PSS (PSS-QoL) was developed. Psychometric testing of PSS-QoL was performed after revising the first draft with feedback of patients (n = 6) and clinicians (n = 4). Convergent construct validity was assessed by correlating the score with the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Euro-QoL 5D (EQ-5D). Reliability was examined by asking patients to complete the questionnaire twice 1-2 weeks apart. An English Version of the PSS-QoL was developed by using standard methodology with forward and back translation. RESULTS: Out of the 75 PSS patients, 91% were female, mean (±SD) age was 58.5 ± 12.5 years. PSS-QoL consists of 25 questions and can be divided into two main categories: physical (discomfort and dryness) and psychosocial. The internal consistency of the PSS-QoL revealed a Crohnbach's α of 0.892. Strong and moderate correlations were found between the PSS-QoL and ESSPRI (corrcoeff = 0.755) and EQ. 5D-pain/discomfort (corrcoeff = 0.531). Reproducibility of the PSS-QoL was high, yielding an ICC of 0.958 (95% CI: 0.926-0.981). CONCLUSIONS: The PSS-QoL is the first specific tool for the assessment of patients' HRQL in PSS and showed good psychometric properties. It may serve as a novel patient-reported outcome measure in future clinical studies.

Joint positions matter for ultrasound examination of RA patients-increased power Doppler signal in neutral versus flat position of hands.

Objective: Position of joints might influence the result of US examination in patients with RA. The purpose of this work was to compare grey-scale (GS) and power Doppler (PWD) findings obtained in neutral vs flat position of hands. Methods: A cross-sectional study of 42 RA patients with active disease. Two dimensional and 3D sonography of wrists and MCP joints were conducted in two different joint positions: neutral position, which is a slight flexion of the fingers with relaxed extensor muscles; and flat position, where all palm and volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the percentage of PWD voxels within a region of interest was calculated. GSS was not quantified using 3D sonography. Results: Compared with neutral position, 2D PWD signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4-80.1%). Inter- and intrareader agreement of PWD results was good (intraclass correlation coefficient: 0.75-0.82). Conclusion: In RA, a neutral position of the hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD signals at wrists and MCP joints, compared with a flat position. Standardization of the scanning procedure is essential for obtaining comparable US results in RA patients in trials and clinical routines.

Novel Senescent Regulatory T-Cell Subset with Impaired Suppressive Function in Rheumatoid Arthritis.

OBJECTIVE: Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far. METHODS: Eighty-four RA patients and 75 healthy controls were prospectively enrolled into the study. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed for phenotypic and functional analyses of Treg subsets. T-cell receptor excision circle (TREC) levels and telomere lengths were determined using RT-PCR. RESULTS: In this paper, we describe the novel CD4+FoxP3+CD28- T-cell subset (CD28- Treg-like cells) in RA patients revealing features of both Tregs and senescent T-cells: Treg surface/intracellular markers such as CD25, CTLA-4, and PD-1 as well as FOXP3 were all expressed by CD28- Treg-like cells, and they yielded signs of premature senescence including reduced TREC levels and an accumulation of γH2AX. CD28- Treg-like could be generated in vitro by stimulation of (CD28+) Tregs with TNF-α. CD28- Treg-like cells insufficiently suppressed the proliferation of effector T-cells and yielded a pro-inflammatory cytokine profile. CONCLUSION: In conclusion, we describe a novel T-cell subset with features of Tregs and senescent non-Tregs. These cells may be linked to an aberrant balance between regulatory and effector functions in RA.

It's more than dryness and fatigue: The patient perspective on health-related quality of life in Primary Sjögren's Syndrome - A qualitative study.

OBJECTIVES: In Primary Sjögren's Syndrome (PSS), there is an apparent lack of data concerning the perspectives of patients, their needs, preferences and difficulties of daily life. This qualitative study was conducted to explore perspectives and needs of patients with PSS that influence health related quality of life (HRQL). METHODS: We recruited 20 PSS patients fulfilling the American-European consensus classification criteria out of the PSS cohort of the Medical University Graz, Austria. In total, 6 focus group sessions (with three to four patients per group) were performed. A modified meaning condensation procedure was used to analyse the data. RESULTS: The interview analysis resulted in 484 meaning units, 254 subconcepts and 86 concepts. The identified concepts were grouped into three dimensions: physical dimension, psychological & emotional challenges and social life & daily living. A dependency between the three categories was identified. The concepts most commonly reported by patients were related to the physical dimension: pain and dryness as well as complaints associated with/provoked by these symptoms. Patients also reported shortness of breath, fatigue und constipation. CONCLUSIONS: This qualitative study underpins that HRQL in PSS patients is affected by several factors. The problems are not limited to dryness, pain and fatigue while the complaints secondary to these symptoms are important to patients with PSS significantly affecting physical, psychological and social life components of HRQL. A disease-specific patient related outcome measures for clinical practice and trials should be developed considering the different aspects of HRQL in PSS.