Clinical influences of anticentromere antibody on primary Sjögren’s syndrome in a prospective Korean cohort

This study was performed to clarify inf luences of anticentromere antibody (ACA) on clinical phenotypes of primary Sjögren’s syndrome (pSS) patients in Korea. Methods: We assessed 318 patients who met the 2016 American College of Rheumatology/ European League Against Rheumatism classification criteria for pSS. All patients were selected from the Korean Initiative of primary Sjögren’s Syndrome (KISS), a prospective cohort. Among them, 53 patients were positive for ACA, while another 265 patients were not. We compared various clinical data including demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values available from the KISS database between the two groups. Results: Patients in the ACA-positive pSS group were older (p = 0.042), and had higher xerostomia inventory scores (p = 0.040), whereas glandular dysfunction represented with Schirmer I test was more severe in the ACA-negative group. More frequent Raynaud’s phenomenon and liver involvement (both p < 0.001) and less articular involvement (p = 0.037) were observed among the EGMs in the ACA-positive group. Less frequency of leukopenia (p = 0.021), rheumatoid factor (p < 0.001), anti-Ro/SSA antibody positivity (p < 0.001), and hypergammaglobulinemia (p = 0.006), as well as higher positivity rates of anti-nuclear antibody and anti- topoisomerase antibody (p < 0.001 and p = 0.006, respectively) were found in the laboratory data in the ACA-positive pSS group. Conclusions: Considering distinct phenotypes in hematological and serological features and EGMs, we should monitor the occurrence of these clinical features among pSS patients with ACA in caution.

Expanded IL-22+ Group 3 Innate Lymphoid Cells and Role of Oxidized LDL-C in the Pathogenesis of Axial Spondyloarthritis with Dyslipidaemia

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4+ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and realtime quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22+ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22+ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22+ ILC3, NKp44 − ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP + cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22+ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22+ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

Patient Perspectives and Preferences Regarding Gout and Gout Management:Impact on Adherence

Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Patient Perspectives and Preferences Regarding Gout and Gout Management:Impact on Adherence

Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Echocardiographic Evaluation of Axial Spondyloarthritis in Korea: Data From the Catholic Axial Spondyloarthritis Cohort

OBJECTIVE: Axial spondyloarthritis (axSpA) is often accompanied by cardiac manifestations, such as valvular heart disease. In this prospective cohort study, we evaluated the incidence of cardiac abnormalities in Korean axSpA patients by echocardiography.METHODS: AxSpA patients were prospectively recruited from a single tertiary hospital. Baseline demographic, clinical, radiographic, and echocardiographic data were collected at the time of enrollment. Echocardiography evaluations were performed with a focus on valvular heart disease and systolic and diastolic function. Logistic regression analyses were used to identify factors associated with diastolic dysfunction in axSpA.RESULTS: A total of 357 axSpA patients were included in the analyses, of whom 78 (21.8%) exhibited diastolic dysfunction, with no reports of systolic dysfunction. Thirteen patients (3.6%) had valvular heart disease, and aortic valve regurgitation (n=5) and mitral valve regurgitation (n=6) were most common. Multivariable logistic regression analyses indicated that older age and higher body mass index (BMI) were positively associated with diastolic dysfunction, whereas human leukocyte antigen (HLA)-B27 positivity was negatively associated with diastolic dysfunction.CONCLUSION: Valvular heart disease is infrequent in Korean axSpA patients. However, diastolic dysfunction is common in axSpA patients, and is significantly associated with older age, higher BMI, and HLA-B27.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.METHODS: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.RESULTS: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.CONCLUSION: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND@#Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.@*METHODS@#RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.@*RESULTS@#Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.@*CONCLUSION@#RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

Type I Interferon Increases Inflammasomes Associated Pyroptosis in the Salivary Glands of Patients with Primary Sjögren's Syndrome

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.

Recurrent Severe Hyponatremia in a Patient with Sjögren’s Syndrome

Sjögren's syndrome (SS) is an autoimmune disease that presents with exocrine gland dysfunction. Renal involvement is common in SS and often results in tubulointerstitial nephritis, renal tubular acidosis, and Fanconi’s syndrome. Electrolyte imbalances are commonly the first symptom of renal involvement of SS. The most common feature of dysnatremia in SS is hypernatremia with diabetes insipidus. However, cases of hyponatremia with syndrome of inappropriate antidiuretic hormone secretion (SIADH) are rarely reported in patients with SS. Herein, we report a case of recurrent severe SIADH in a patient with SS.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND@#Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.@*METHODS@#RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.@*RESULTS@#Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.@*CONCLUSION@#RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

Type I Interferon Increases Inflammasomes Associated Pyroptosis in the Salivary Glands of Patients with Primary Sjögren's Syndrome

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.

Recurrent Severe Hyponatremia in a Patient with Sjögren’s Syndrome

Sjögren's syndrome (SS) is an autoimmune disease that presents with exocrine gland dysfunction. Renal involvement is common in SS and often results in tubulointerstitial nephritis, renal tubular acidosis, and Fanconi’s syndrome. Electrolyte imbalances are commonly the first symptom of renal involvement of SS. The most common feature of dysnatremia in SS is hypernatremia with diabetes insipidus. However, cases of hyponatremia with syndrome of inappropriate antidiuretic hormone secretion (SIADH) are rarely reported in patients with SS. Herein, we report a case of recurrent severe SIADH in a patient with SS.

Rheumatoid arthritis is associated with early tooth loss: results from Korea National Health and Nutrition Examination Survey V to VI

BACKGROUND/AIMS@#To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss.@*METHODS@#The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed.@*RESULTS@#The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted β, 0.20; p = 0.042).@*CONCLUSIONS@#RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.

Erratum: Effects of Individual Education Using a Treating-to-target Strategy in Patients with Rheumatoid Arthritis

The original version of this article contained an error of the ORCID identifier of corresponding author (Ji Hyeon Ju).

Insulin resistance is an independent predictor of erectile dysfunction in patients with gout

BACKGROUND/AIMS: Gout is associated with metabolic disorders that are important risk factors for cardiovascular disease and erectile dysfunction (ED). We aimed to identify independent predictors of ED in patients with gout. METHODS: From August 2014 to August 2015, male outpatients who were being treated for gout in our rheumatology clinic and healthy males without any history of inflammatory disease (control group) were studied. ED was assessed in participants using the five-item version of the International Index of Erectile Function questionnaire. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA-IR). Logistic regression analysis was performed to determine the effect of variables on ED risk in all of the study subjects and in patients with gout. RESULTS: We analyzed 80 patients with gout and 70 healthy controls. The median age of patients with gout was 52 years and median disease duration was 120 months. Gout patients were more likely to have ED than controls (55.3% vs. 41.4%, p < 0.047). After adjustment for confounding factors, only HOMA-IR was significantly associated with ED (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.05 to 3.15). Gout patients with ED were more likely to be older (p < 0.001), have higher HOMA-IR (p = 0.048), and have lower glomerular filtration rate (p = 0.038) than those without ED. Multivariate logistic regression analysis showed that HOMA-IR was an independent predictor for ED (OR, 1.62; 95% CI, 1.03 to 2.82) in gout patients. CONCLUSIONS: IR is an independent predictor of ED in patients with gout.

Clinical outcomes and pathological characteristics of immunoglobulin G4-related ophthalmic disease versus orbital inflammatory pseudotumor

BACKGROUND/AIMS: This study investigated the clinical and pathological features of immunoglobulin G4 (IgG4)-related ophthalmic disease. To clarify the features, we compared IgG4-related ophthalmic disease and orbital inflammatory pseudotumor. METHODS: We retrospectively reviewed the medical records of 103 patients who were initially diagnosed with orbital inflammatory pseudotumor, and identified 16 cases in which the diagnosis was based on surgical biopsy and for which data in medical records were sufficient for analysis. Immunohistochemical staining of pathological specimens for IgG and IgG4 was performed. Finally, six of IgG4-related ophthalmic disease patient and 10 of orbital inf lammatory pseudotumor patient were analyzed. RESULTS: The IgG4-related ophthalmic disease group had more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than the orbital inflammatory pseudotumor group. Collagenous fibrosis and lacrimal gland involvement were significantly more frequent in the IgG4-related ophthalmic disease group. Dense lymphocyte infiltration, obliterative phlebitis, and bilateral lesions were more frequent in IgG4-related ophthalmic disease, but the differences were not significant. The recurrence-free period was shorter in the IgG4-related ophthalmic disease group (p = 0.035). CONCLUSIONS: The location of the lesion (lacrimal gland), count and ratio of IgG4-positive plasma cells, and collagenous fibrosis aid the diagnosis of IgG4-related ophthalmic disease in patients with idiopathic orbital mass-like lesions. In addition, maintenance therapy should be considered in patients with IgG4-related ophthalmic disease to prevent recurrence.

Circulating CCR7(lo)PD-1(hi) Follicular Helper T Cells Indicate Disease Activity and Glandular Inflammation in Patients with Primary Sjögren's Syndrome

Since primary Sjögren's syndrome (pSS) is an autoummune disease of B cell hyperactivity and pathologic autoantibody response, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are suggested to be key players in pSS. We examined subsets of Tfh and Tfr cells from the blood in pSS patients, and whether these subsets represent disease activity, glandular inflammation, or autoantibody responses in pSS. Circulating Tfh and Tfr cells, along with their specific subsets, were identified from the peripheral blood of 18 pSS patients and 14 age- and sex-matched healthy controls (HCs) using flow cytometry analysis. Blood Tfr and Tfh cell ratios were increased in pSS patients compared with HCs. The CCR7(lo)PD-1(hi) subset of circulating Tfh cells was increased in pSS patients with high degree of focal lymphocytic sialadenitis; whereas circulating Tfh cells did not differ between pSS patients and HCs. The frequency of CCR7(lo)PD-1(hi) Tfh cells was significantly correlated with disease activity scores and differentiated B cells. PD-1 expression on blood Tfh and Tfr cells showed positive correlations with IL-21 in pSS. Increasing trend of blood Tfr cells was observed in pSS patients, and blood Tfr cells (particularly Th1 and Th17 subsets) represented hypergammaglobulinemia in pSS. In summary, circulating CCR7(lo)PD-1(hi) Tfh cells indicated disease activity and glandular inflammation in pSS. Circulating Tfr cells, shifted toward Th1 and Th17 subsets, indicated ongoing IgG production in pSS. Subsets of circulating Tfh or Tfr cells could be biomarkers for disease monitoring and patient stratification in pSS.

Effects of Individual Education Using a Treating-to-target Strategy in Patients with Rheumatoid Arthritis

OBJECTIVE: To examine effects of an individual education program using the treating rheumatoid arthritis to target (RA T2T) strategy in patients with moderate-severe rheumatoid arthritis. METHODS: Patients were assigned randomly to an educational intervention (n=33) or conventional care group (n=33). The intervention was a nurse-delivered 9-month educational program consisting of 3 monthly sessions and monthly telephone counseling. The assessments occurred at the baseline and every 3 months in both groups, but only the intervention group completed the 9-month education follow-up. The outcome variables included the disease activity (DAS28), functional disability (KHAQ), fatigue (FACIT-Fatigue), and quality of life (SF-36). Repeated measures ANOVA and a Bonferroni multiple comparison were used to evaluate the outcome variables comparing the groups and follow-up times. RESULTS: Significant interactions were observed between the groups and follow-up times in the disease activity (p=0.041), fatigue (p=0.042), and physical (p=0.006) and mental (p=0.031) health-related quality of life, but there was no significant interaction in the functional disability (p=0.110). Significant differences were noted between the groups at the 9-month period (p=0.048) in disease activity and fatigue, and at the 6-month (p=0.023) and 9-month periods (p=0.027) in the physical health-related quality of life. CONCLUSION: This education program using the RA T2T strategy had significant benefits on the disease activity, fatigue, and quality of life in patients with moderate to severe rheumatoid arthritis, and the results suggested that this contributed to positive clinical outcomes as a good practical nursing intervention.

Sleep Quality Independently Affects Health-related Quality of Life and Cognitive Function in Korean Female Patients with Rheumatoid Arthritis: a Case-control Study

BACKGROUND: This study aimed to address sleep quality in patients with rheumatoid arthritis (RA) and to determine how it affects health-related quality of life (HRQoL) and cognitive function. METHODS: One hundred and twenty-three patients with RA and 76 healthy controls were enrolled in this study. Sleep quality was assessed using the Korean version of the Pittsburgh Sleep Quality Index (PSQI). Cognitive function and HRQoL was evaluated by a Korean-Montreal Cognitive Assessment (MoCA-K) and 36-item Short-Form Health Survey (SF-36), respectively. Other clinical, demographic, and laboratory data were obtained from retrospective medical chart review. RESULTS: More patients in the RA group reported poor sleep quality (PSQI > 5) than in the control group (61% [75/123] vs. 39.5% [30/76]; P = 0.003). Total PSQI was also significantly higher in the RA group (median [interquartile range], 7 [5–11] vs. 5 [3–6.75]; P = 0.001). Total PSQI score negatively correlated with MoCA-K score (Spearman's rho (r) = −0.223; P = 0.003) with a physical component summary (PCS) of SF-36 (r = −0.221; P = 0.003) and a mental component summary (MCS) of SF-36 (r = −0.341; P < 0.001), which means that poor sleep quality was associated with poor cognitive function and low HRQoL. CONCLUSION: The findings of this study suggest that poor sleep quality is an independent risk factor for low HRQoL and cognitive dysfunction. Efforts to improve the sleep quality of RA patients seem to be an important aspect of integrative treatment for RA.

Interleukin-17 Enhances Germinal Center Formation and Immunoglobulin G1 Production in Mice

OBJECTIVE: Interleukin (IL)-17 is a pro-inflammatory cytokine that has pleiotropic effects on multiple target cells and thereby contributes to the development of immune-mediated inflammatory disorders. However, the role of IL-17 in the humoral immune response has not been clearly elucidated. METHODS: Mice deficient in IL-17A (IL-17A knockout [KO] mice) and wild type (WT) C57BL/6 mice were compared. Distinct B cell (mature/precursor and marginal zone/follicular) and plasma cell populations were compared using fluorescence-activated cell sorting (FACS) and confocal immunostaining. Immunoglobulin production was assessed by enzyme-linked immunosorbent assay. RESULTS: There was no difference in B cell and plasma cell populations between IL-17A KO and WT mice. However, after T cell-dependent antigen challenge, IL-17A KO mice produced lower levels of immunoglobulin (Ig)G1 than wild-type animals. IL-17A KO mice also showed reduced germinal center (GC) formation and lower expression of activation-induced cytidine deaminase, the essential enzyme for class switch recombination (CSR). IL-17 had no effect on the proliferation or survival of naïve B cells in in vitro functional studies. However, IL-17 treatment promoted naïve B cell differentiation into plasma cells in synergy with IL-4, although IL-17 alone had no effect. CONCLUSION: Our findings suggest that IL-17 contributes to the humoral immune response by enhancing GC formation, CSR to IgG1, and plasma cell differentiation in synergy with IL-4.