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We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count. [ABSTRACT FROM AUTHOR]

The concept of progressive pulmonary fibrosis (PPF) has been introduced to predict the diverse prognosis of interstitial lung disease (ILD). However, the incidence and effect of PPF on outcomes in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) need to be elucidated. This study reviewed 197 patients with CTD-ILD. Symptomatic worsening, pulmonary function decline, and radiological deterioration were investigated to assess the fulfillment of PPF diagnostic criteria. Clinical outcomes, including mortality, were compared based on the presence or absence of PPF. The median follow-up duration was 17.4 months. The mean age of the patients was 64.0 years, and 60.9% were female. Among the underlying CTDs, rheumatoid arthritis (42.1%), inflammatory myositis (19.8%), and systemic sclerosis (13.2%) were the most common. Of the 197 patients, 37 (18.8%) met the diagnostic criteria for PPF during the follow-up period. Even after adjusting for other significant risk factors, PPF was independently associated with mortality [hazard ratio (HR) 3.856; 95% confidence interval (CI) 1.387–10.715; P = 0.010] and baseline albumin was marginally significantly associated with mortality (HR 0.549; CI 0.298–1.010; P = 0.054). The median survival was also significantly shorter in the PPF group than in the non-PPF group (72.3 ± 12.9 vs. 126.8 ± 15.5 months, P < 0.001). Baseline KL-6 ≥ 1000 (U/mL) was a significant risk factor for PPF (HR 2.885; CI 1.165–7.144; P = 0.022). In addition to increased mortality, the PPF group had significantly higher rates of respiratory-related hospitalizations, pneumonia, acute exacerbations, and weight loss than the non-PPF group. PPF is a significant prognostic indicator in patients with CTD-ILD. Thus, healthcare professionals should know that patients with CTD-ILD are at risk of PPF. [ABSTRACT FROM AUTHOR]

Objective: To determine the prognostic significance of proteinuria monitoring in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: We retrospectively analyzed the data of kidney biopsy-confirmed patients with AAV. Proteinuria was evaluated by a urine dipstick test. Poor renal outcome was defined as stage 4/5 chronic kidney disease (CKD) (estimated glomerular filtration rate < 30 mL/min/1.73 m2). Results: We enrolled 77 patients with a median follow-up duration of 36 months (interquartile range, 18–79) in this study. Excluding 8 patients on dialysis at 6 months, 59/69 (85.5%) achieved remission after induction therapy. Patients were then divided into two groups according to the presence of proteinuria at 6 months after induction therapy (n = 29 with proteinuria, 40 without proteinuria). There was no significant difference in the rate of relapse or death according to the presence of proteinuria (p = 0.304 relapse, 0.401 death). In contrast, patients with proteinuria had significantly lower kidney function than those without proteinuria (41 vs. 53.5 mL/min/1.73 m2, p = 0.003). Multivariate analysis revealed that eGFR values at 6 months (hazard ratio [HR] 0.925; 95% CI 0.875–0.978, p = 0.006) and proteinuria at 6 months (HR 4.613; 95% CI 1.230–17.298, p = 0.023) were significantly associated with stage 4/5 CKD. Conclusion: The presence of proteinuria at 6 months after induction therapy and low renal function was significantly associated with a higher risk of stage 4/5 CKD in patients with AAV. Monitoring for proteinuria after induction therapy may help predict poor renal outcomes in patients with AAV. [ABSTRACT FROM AUTHOR]

Background: Aortic regurgitation (AR) is a common cardiovascular complication in patients with Takayasu arteritis (TAK), and complication after aortic valve surgery (AVS) is not rare. This study aimed to identify the long-term postoperative outcomes for significant AR in patients with TAK compared with those in patients without TAK. Methods: We included 35 patients with TAK with moderate-to-severe AR who underwent AVS and compared their postoperative outcomes with those of 105 age- and operation period-matched patients with severe AR but without TAK. The risk factors for poor outcomes [all-cause death and major adverse cardiac and cerebrovascular events (MACCE)] in patients with TAK were analyzed using multivariate Cox regression. Results: The 10-year overall survival rate was 70.5% in patients with TAK and 89.4% in those without TAK (p = 0.048). The MACCE and reoperation rates were significantly higher in patients with TAK (10-year freedom from MACCE, 58.2% vs. 86.4% [p < 0.001]; 10-year freedom from reoperation, 64.5% vs. 98.3% [p < 0.001]). Eighteen of the 35 patients with TAK (51.4%) had poor outcomes, and multivariate analysis revealed that significant coronary artery involvement [hazard ratio (HR), 4.178; 95% confidence interval (CI), 1.222–14.282; p = 0.023] and decreased estimated glomerular filtration rate (HR, 0.968; 95% CI 0.947–0.989; p = 0.003) were associated with poor outcomes. Conclusion: The long-term postoperative outcomes for AR were poorer in patients with TAK than in those without TAK. The poor outcomes in patients with TAK were associated with coronary artery involvement and decreased renal function. [ABSTRACT FROM AUTHOR]

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006–5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression. [ABSTRACT FROM AUTHOR]

Objective: Kidney biopsy is essential for the diagnosis and classification of lupus nephritis. Percutaneous biopsy has a risk of bleeding-related complications; however, data on the risk of percutaneous kidney biopsy in patients with systemic lupus erythematosus (SLE) are scarce. In this study, we aimed to investigate the rate of bleeding-related complications and to examine the risk factors for complications of kidney biopsy in patients with systemic lupus erythematosus (SLE). Methods: We retrospectively reviewed the medical records of patients with SLE who underwent ultrasound-guided percutaneous kidney biopsy between 2002 and 2020 at a tertiary referral center. Minor complications were defined as hematoma and passing hematuria not requiring an intervention. Major complications included bleeding events that required interventions after the biopsy. Statistical analysis with a multivariate logistic regression model was performed. Results: In a total of 277 patients with SLE, the rate of overall bleeding-related complications after kidney biopsy was 19.9% (minor 13.0%; major 6.9%). Among patients with major complications, 84.2% needed blood transfusion alone without embolization or surgery, whereas the remaining three patients needed embolization for bleeding control. Multivariate analysis revealed that thrombocytopenia (odds ratio [OR] 7.186, 95% confidence interval [CI] 2.315–22.300), and low eGFR (OR 3.478, 95% CI 1.094–11.056) were significantly associated with the risk of major bleeding-related complications after kidney biopsy. Conclusion: Percutaneous kidney biopsy is accompanied by the risk of bleeding-related complications; however, most events in our study did not require vascular intervention for bleeding control. Low platelet count and low estimated glomerular filtration rate (eGFR) significantly increase the risk of complications after kidney biopsy in patients with SLE. Key Points • The rate of overall bleeding-related complications after kidney biopsy was about 20% of patients with SLE. • The most commonly observed events were gross hematuria followed by blood transfusion. • Thrombocytopenia and poor kidney function areis an important risk of bleeding-related complications after kidney biopsy. [ABSTRACT FROM AUTHOR]

Purpose: We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis. Methods: We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured. Results: Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan. Conclusions: The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ. [ABSTRACT FROM AUTHOR]

Introduction: To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). Methods: Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated. Results: Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5–5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4–29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6–21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence. Conclusion: JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated. Key Points • JAK inhibitor was generally continued or re-administered after HZ reactivation • Most patients receiving JAK inhibitor after the HZ episode did not experience recurrence of HZ • Resuming JAK inhibitor following HZ seems to be safe [ABSTRACT FROM AUTHOR]

Objective: Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF. Methods: We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients. Results: CTD developed in 15 patients at a median of 2.1 years (range 1.2–4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001). Conclusion: Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD. [ABSTRACT FROM AUTHOR]

There are limited studies regarding the safety of methotrexate (MTX) in patients with reduced renal function. This study aimed to investigate methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA) and renal dysfunction. This retrospective cohort study included patients with RA and renal dysfunction. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. We classified the patients into two groups according to the onset of renal dysfunction: newly and previously developed group. MTX-associated toxicity included renal toxicity, hepatotoxicity, serious infection, pancytopenia, leukopenia, thrombocytopenia and mucositis. Cox analysis was performed to determine the factors associated with toxicity. The study included 120 patients with RA and renal dysfunction receiving MTX (66: newly developed; 54: previously developed). The median eGFR was 52.1 mL/min/1.73 m2 [IQR 47.1–57.3]. Thirty-five patients (29.2%) experienced toxicity, and the median time to toxicity events was 23 months (IQR 10–57). Toxicity was distributed as follows: leukopenia (10%, 12/120), renal toxicity (5.8%, 7/120), hepatotoxicity (7.5%, 9/120), serious infection (8.3%, 10/120), pancytopenia (5.0%, 6/120), thrombocytopenia (5.8%, 7/120), and mucositis (5.8%, 7/120). The toxicity rate did not differ significantly between newly and previously developed group [23/66 (34.8%) vs. 12/54 (22.2%), P = 0.130]. Multivariate analysis revealed that hydroxychloroquine use (HR 0.425, 95% CI 0.212–0.853, P = 0.016), baseline eGFR (HR 0.938, 95% CI 0.890–0.988, P = 0.015) and being female (HR 10.538, 95% CI 1.375–80.793, P = 0.023) were associated with MTX-related toxicity. Toxicity occurred in approximately 30% of patients with RA and renal dysfunction receiving MTX treatment. Hydroxychloroquine use exhibited a protective effect against MTX-associated toxicity development. [ABSTRACT FROM AUTHOR]

We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592–0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480–0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the risk factors of renal flare in patients with membranous lupus nephritis (class V lupus nephritis). Biopsy-proven pure membranous lupus nephritis patients diagnosed between January 1997 and September 2017 were studied. We assessed and compared the clinical and pathological parameters between patients who experienced renal flare and those who did not. To identify risk factors of renal flare, multivariable Cox proportional hazard regression analysis was performed. Out of the 53 patients with pure membranous lupus nephritis, 17 patients (32.1%) experienced renal flare during a median follow-up of 121.5 months (range 44.4–196.9). Patients who experienced renal flare had significantly higher proportion of tubulointerstitial inflammation (76.5% vs. 36.1%, p = 0.006) and tubular atrophy/interstitial fibrosis (70.6% vs. 27.8%, p = 0.003) at baseline. In multivariable Cox proportional hazard regression analysis, the presence of tubulointerstitial inflammation [adjusted hazard ratio (HR) 5.532, 95% confidence interval (CI) 1.722–17.776, p = 0.004] and tubular atrophy/interstitial fibrosis (adjusted HR 4.328, 95% CI 1.450–12.916, p = 0.009) at baseline was significantly associated with increased risk of renal flare. The presence of tubulointerstitial inflammation and tubular atrophy/interstitial fibrosis is associated with increased risk of renal flare in patients with membranous lupus nephritis. [ABSTRACT FROM AUTHOR]

Tubulointerstitial inflammation (TI) has prognostic significance in the renal outcomes of lupus nephritis. Here, we aimed to determine whether non-albumin proteinuria is associated with TI severity and with the renal response in lupus nephritis. We included patients with biopsy-confirmed lupus nephritis at a tertiary medical center in Korea from January 2011 to April 2017. Patients in whom the urine protein/creatinine ratio (uPCR) and the urine albumin/creatinine ratio (uACR) were measured simultaneously were included. Laboratory data and renal pathology were reviewed. Non-albumin proteinuria was calculated by subtracting uACR from uPCR. The renal response was assessed by the amount of proteinuria present at 6 months after treatment with immunosuppressants. Logistic regression analyses were performed to identify factors associated with TI severity and renal response. Out of 45 patients, 36 (80%) had no-to-mild TI, whereas 9 (20%) had moderate-to-severe TI. Proliferative (class III ± V/IV ± V) and nonproliferative (class II/V) glomerulonephritis (GN) were present in 38 (84.4%) and 7 (15.6%) patients, respectively. In the logistic regression analyses, non-albumin proteinuria (uPCR − uACR) was associated with moderate-to-severe TI (odds ratio [OR] 3.166, 95% confidence interval [95% CI] 1.145-8.757, p = 0.026) and was inversely associated with complete renal response (adjusted OR 0.180, 95% CI 0.045-0.718, p = 0.015). In lupus nephritis, non-albumin proteinuria was associated with TI severity and with poor renal response after immunosuppressive treatment. Thus, the determination of non-albumin proteinuria can provide clinically valuable information on lupus nephritis. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate risk factors for cytopenia when a prophylactic dose of trimethoprim-sulfamethoxazole (TMP-SMX) was co-administered with methotrexate (MTX). Patients who received MTX with or without a prophylactic dose of TMP-SMX were included. Patients who received a therapeutic dose of TMP-SMX were excluded. The MTX-alone and MTX with TMP-SMX groups (MTX group and MTX + TMP-SMX group, respectively) were matched in a 4:1 ratio according to age, creatinine level, mean corpuscular volume and MTX dose. Cytopenia was defined as a haemoglobin level decrease by > 2 g/dl, platelet count of < 150,000/mm3 or white blood cell count of < 3500/mm3. The Cox proportional hazards model was used to evaluate risk factors for cytopenia in patients administered with MTX. The incidence of cytopenia did not significantly differ between the MTX group and MTX + TMP-SMX group (5.0 vs 5.7%, p > 0.999). According to the Cox proportional hazards model, chronic liver disease (hazard ratio [HR] 5.829, 95% confidence interval [CI] 1.211-28.063, p = 0.028) was associated with an increased risk of cytopenia. However, the concomitant use of a prophylactic dose of TMP-SMX (HR 1.717, 95% CI 0.352-8.371, p = 0.504) was not significantly associated with an increased risk of cytopenia. Compared with the use of MTX alone, the concomitant use of MTX with a prophylactic dose of TMP-SMX was not significantly associated with an increased risk of cytopenia. Thus, a prophylactic dose of TMP-SMX can be safely used with MTX. [ABSTRACT FROM AUTHOR]

To prevent spinal progression in ankylosing spondylitis, initiating TNF-inhibitor treatment as early as possible is suggested. However, the outcomes are inconsistent in previous clinical studies. Here, we investigated the effect of TNF inhibition alone on spinal progression when used during arthritis development in a murine model. We injected 8-week-old SKG mice with curdlan (curdlan group). We injected adalimumab at 3 and 9 weeks after the first curdlan injection (ADA group). The clinical scores of peripheral arthritis decreased in the ADA group at 3 weeks after first adalimumab injection. Using positron emission tomography–magnetic resonance imaging and histologic examination, spinal inflammation was observed in the curdlan group, and was significantly deceased in the ADA group. However, spinal osteoblast activities by imaging using OsteoSense 680 EX and bone metabolism-related cytokines such as receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, Dickkopf-1, and sclerostin levels except IL-17A level were not different between the two groups. We conclude that treating TNF inhibitor alone reduced peripheral arthritis score and spinal inflammation in curdlan-injected SKG mice but did not decrease the spinal osteoblast activity, suggesting little effect on spinal ankylosis. [ABSTRACT FROM AUTHOR]

Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote TH17 cell differentiation. In the TH17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and TH17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of TH17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of TH17 cell differentiation, which is dependent on IL-6 secretion. [ABSTRACT FROM AUTHOR]

Interleukin-32 gamma (IL-32γ) is a recently discovered cytokine that is elevated in inflamed tissues and contributes to pathogenic features of bone in human inflammatory rheumatic diseases. Nevertheless, the role of IL-32γ and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32γ in bone remodeling and the hypothetical correlation between IL-32γ and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32γ showed reduced bone loss with advancing age, increased bone formation, and high osteogenic capacity of osteoblast compared to wild-type (WT) mice through the upregulation of miR-29a, which caused a reduction of Dickkopf-1 (DKK1) expression. IL-32γ TG mice were protected against ovariectomy (OVX)induced osteoporosis compared with WT mice. Decreased plasma IL-32γ levels were associated with bone mineral density (BMD) in human patients linked to increased DKK1 levels. These results indicate that IL-32γ plays a protective role for bone loss, providing clinical evidence of a negative correlation between IL-32γ and DKK1 as bone metabolic markers. [ABSTRACT FROM AUTHOR]