Disordered Balance of T-Cell Subsets in Arterial Tertiary Lymphoid Organs in Immunoglobulin G4-Related Vascular Disease.

BACKGROUND: Arterial/aortic tertiary lymphoid organs (ATLOs), characterized by germinal centers, control local arterial immune responses. T follicular helper cells (Tfh), resident in germinal centers, regulate immunoglobulin production and germinal center development. They consist of Tfh1, Tfh2, and Tfh17 subsets. T follicular regulatory (Tfr) cells possess suppressive functions as regulatory T cells and migrate into germinal centers. Immunoglobulin G4 (IgG4)-related diseases manifest in vascular lesions as frequently formed inflammatory aneurysms (IgG4-related abdominal aortic aneurysm [IgG4-AAAs]). IgG4-AAAs contain several ATLOs. METHODS AND RESULTS: We performed whole-slide immunohistochemical image analysis in surgical specimens of IgG4-AAAs (n=21), non-IgG4-related inflammatory AAAs (n=17), atherosclerotic AAAs (n=10), and Takayasu arteritis (n=5). IgG4-AAA was characterized by numerous, large, irregular-shaped ATLOs, and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared with others. The morphologic abnormalities (in number, area, and form) of ATLOs in IgG4-AAAs and the increased number of Tfr cells are closely related to the activity of IgG4-related diseases. All T-cell subsets were more enriched within ATLOs than outside ATLOs. In particular, an increase in Tfr cells in IgG4-AAAs was associated with ATLO formation. Increased Tfh17 cells were found in Takayasu arteritis, and atherosclerotic AAA and non-IgG4-related inflammatory AAAs were characterized by increased Tfh1 cells. CONCLUSIONS: In the classification of vascular lesions, considering the imbalance in T-cell subsets, IgG4-AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs.

[Development of coronary artery disease in a young adult with Takayasu's arteritis: the lesser, the better]. / Sviluppo di malattia coronarica in giovane paziente affetto da arterite di Takayasu: the lesser, the better.

Large vessel vasculitis, such as Takayasu's arteritis (TA), is a rare inflammatory disease affecting multiple vascular districts including the coronary arteries, producing either stenosis and/or aneurysms: these lesions can be found in the same patient and also in the same vessel, with potentially devastating effects. Moreover, TA often affects young people, in the midst of their work and social activity. Ischemic heart disease is the leading cause of cardiovascular mortality in Western countries and is mainly due to coronary atherosclerosis, whose etiopathogenesis is multifactorial and is closely related to the concomitant presence of classic cardiovascular risk factors and inflammation of the vessel wall. We report the case of a young, physically active adult with multivessel coronary artery disease developed in the context of a TA bursted 7 years before and currently in clinical remission. This complex case required a careful literature review and a multidisciplinary approach, since the best treatment option for coronary lesions induced by TA has not been established: a "watchful waiting" strategy was eventually adopted, considering the poor outcome of both percutaneous and surgical revascularization in this group of patients.

Arterial wall fibrosis in Takayasu arteritis and its potential for therapeutic modulation.

Arterial wall damage in Takayasu arteritis (TAK) can progress despite immunosuppressive therapy. Vascular fibrosis is more prominent in TAK than in giant cell arteritis (GCA). The inflamed arterial wall in TAK is infiltrated by M1 macrophages [which secrete interleukin-6 (IL-6)], which transition to M2 macrophages once the inflammation settles. M2 macrophages secrete transforming growth factor beta (TGF-ß) and glycoprotein non-metastatic melanoma protein B (GPNMB), both of which can activate fibroblasts in the arterial wall adventitia. Mast cells in the arterial wall of TAK also activate resting adventitial fibroblasts. Th17 lymphocytes play a role in both TAK and GCA. Sub-populations of Th17 lymphocytes, Th17.1 lymphocytes [which secrete interferon gamma (IFN-γ) in addition to interleukin-17 (IL-17)] and programmed cell death 1 (PD1)-expressing Th17 (which secrete TGF-ß), have been described in TAK but not in GCA. IL-6 and IL-17 also drive fibroblast activation in the arterial wall. The Th17 and Th1 lymphocytes in TAK demonstrate an activation of mammalian target organ of rapamycin 1 (mTORC1) driven by Notch-1 upregulation. A recent study reported that the enhanced liver fibrosis score (derived from serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and pro-collagen III amino-terminal pro-peptide) had a moderate-to-strong correlation with clinically assessed and angiographically assessed vascular damage. In vitro experiments suggest the potential to target arterial wall fibrosis in TAK with leflunomide, tofacitinib, baricitinib, or mTORC1 inhibitors. Since arterial wall inflammation is followed by fibrosis, a strategy of combining immunosuppressive agents with drugs that have an antifibrotic effect merits exploration in future clinical trials of TAK.

Sudden death due to Takayasu arteritis complication associated with situs inversus totalis: A case discovered at autopsy.

Takayasu arteritis is a rare pathology that usually has general and atypical signs that make its diagnosis difficult. These characteristics can delay diagnosis, thus leading to complications and death. We, herein, report an autopsy case of a 25-year-old female patient with a history of multiple consultations for dyspnea. During these consultations, no diagnosis was made. She was found unconscious near her home and shortly after, she was declared dead. Forensic autopsy revealed superficial traumatic lesions. Internal examination revealed complete situs inversus. Multiple bilateral pleural adhesions and bilateral moderate effusion were found. The heart was heavy with thickening of the aortic wall (1.1cm), carotid arteries, and pulmonary trunk, associated with a large aortic valve and evidence of leakage. Histological examination of the aorta and its major branches showed features of panarteritis with segmental involvement. The vascular wall was thick with lymphoplasmacytic infiltrate and giant cells involving mainly the medio-adventitial junction. Disruption of the elastic lamina and reactive fibrosis in the intima were also noted. Diagnosis of large vessel vasculitis and particularly Takayasu arteritis was made. Death was therefore attributed to heart failure due to aortic insufficiency as a complication of Takayasu arteritis.

PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study.

OBJECTIVE: To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis. METHODS: Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated. RESULTS: At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P < 0.01) and CRP level (r = 0.69, P < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up. CONCLUSION: PETVAS showed good performance in predicting new lesions in Takayasu arteritis.

Nationwide clinical and epidemiological study of large-vessel vasculitis in Japan in 2017.

OBJECTIVE: We conducted a nationwide epidemiological study to estimate the number of patients with Takayasu arteritis (TAK) and giant cell arteritis (GCA) in Japan and to describe the clinical characteristics of these patients. METHODS: The first survey was designed to estimate the number of patients with TAK and GCA who were treated at medical institutions in Japan in 2017. The second survey was designed to collect data on the clinical characteristics of the patients who were reported in the first survey. RESULTS: Of the 3495 institutions selected for the first survey, 1960 (56.1%) responded. The number of patients with clinically diagnosed TAK and GCA was estimated to be 5320 (95% confidence interval, 4810-5820) and 3200 (95% confidence interval, 2830-3570), respectively. Aortic regurgitation was reported in 35% of patients with TAK, and eye-related comorbidities were observed in 30.4% of patients with GCA. The common carotid and internal carotid arteries were the most frequently involved in patients with TAK (62.7%). Subclavian artery lesions and thoracic or abdominal aorta lesions were reported in 31% and 42.6% of patients with GCA, respectively. CONCLUSIONS: The number of patients with TAK and GCA was estimated simultaneously, and significant differences in clinical characteristics were observed between the two diseases.

Monocyte subsets and monocyte-related chemokines in Takayasu arteritis.

The pathogenesis of Takayasu arteritis (TAK) is poorly understood and no previous studies have analyzed monocytes in TAK. This study evaluated monocyte subsets and monocyte-related chemokines in the peripheral blood of TAK patients and healthy controls (HC). Monocyte subsets were identified as classical (CD14+CD16-), intermediate (CD14+CD16dim), and non-classical (CD14dimCD16high) in the peripheral blood. The chemokines CCL (C-C chemokine ligand)2, CCL3, CCL4, CCL5, CCL7, CXCL (C-X-C motif ligand)10, and CX3CL (C-X3-C motif ligand)1 were measured in the sera. Thirty-two TAK patients and 30 HC were evaluated. Intermediate monocytes were higher in TAK than HC [25.0 cells ×106/L (16.7-52.0) vs. 17.2 cells ×106/L (9.2-25.3); p = 0.014]. Active disease was associated with monocytosis (p = 0.004), increased classical (p = 0.003), and intermediate (p < 0.001) subsets than HC. Prednisone reduced the percentage of non-classical monocytes (p = 0.011). TAK patients had lower CCL3 (p = 0.033) and CCL4 (p = 0.023) levels than HC, whereas CCL22 levels were higher in active TAK compared to the remission state (p = 0.008). Glucocorticoids were associated with lower CXCL10 levels (p = 0.012). In TAK, CCL4 correlated with total (Rho = 0.489; p = 0.005), classical and intermediate monocytes (Rho = 0.448; p = 0.010 and Rho = 0.412; p = 0.019). In conclusion, TAK is associated with altered counts of monocyte subsets in the peripheral blood compared to HC and CCL22 is the chemokine with the strongest association with active disease in TAK.

"Coexistence of IgA nephropathy and renal artery stenosis in Takayasu arteritis: case report and literature review".

Although Takayasu arteritis (TAK) is a form of large vessel vasculitis, complications of glomerulonephritis have occasionally been observed, with mesangial proliferative glomerulonephritis as the most common. The aim of this work was to present a case-based review regarding the association of glomerulonephritis and IgA nephropathy (IgAN) with TAK. A literature search was carried out using the PubMed and Scopus databases for articles published in English, and the Ichu-shi Web for Japanese. A 34-year-old Japanese man was evaluated for proteinuria, and IgAN was diagnosed by renal biopsy. Simultaneously, aortic wall thickening and right renal artery stenosis confirmed a coexisting TAK. Prednisolone and methotrexate improved both diseases, and percutaneous transluminal renal angioplasty resulted in right renal artery reopening. Our case and literature review revealed that membranous proliferative glomerulonephritis and IgAN are common in eastern Asia, while focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis are common in other regions. The incidence of IgAN is higher in TAK cases and is mostly reported in Asia. Abdominal aortic involvement and renal artery stenosis are common in cases with preceding TAK. IgAN could be related to the cytokine network involving interleukin-6, suggesting the usefulness of tocilizumab in patients with TAK accompanied by IgAN. The type of glomerulonephritis complicated with TAK differs among regions, and patients with TAK are more likely to experience IgAN than the healthy population.

Ultrasonography and contrast-enhanced ultrasound for activity assessment in 115 patients with carotid involvement of Takayasu arteritis.

OBJECTIVES: To evaluate the efficacy of ultrasound and contrast-enhanced ultrasound (CEUS) in disease activity assessment of Takayasu arteritis (TA) with carotid involvement. METHODS: This is a cohort study of 115 patients of TA with carotid involvement. We investigated correlations between clinical data, sonographic features, and CEUS enhancement at the site most prominent lesion of each patient. Disease activity was assessed by the National Institute of Health Kerr criteria. Sonographic findings were compared with follow-up examinations. CEUS was repeated after a 3-7 months interval in 35 patients to evaluate change of CEUS enhancement after treatment. RESULTS: Extensiveness of CEUS enhancement at most prominent carotid lesions had significant correlations with disease activity by the Kerr criteria (P < .001). The specificity of extensive enhancement for indicating active disease was 95%, while sensitivity was 67%. Patients with active disease showed greater arterial wall thickness and more prominent reduction of arterial wall thickness after treatment. Most of the patients (68%) with subsided active disease after treatment featured decrease of CEUS enhancement. CONCLUSIONS: Extensiveness of enhancement by CEUS and arterial wall thickness by ultrasonography may be useful markers for initial and follow-up assessment of disease activity of TA with common carotid artery involvement.

A novel molecular mechanism of vascular fibrosis in Takayasu arteritis: macrophage-derived GPNMB promoting adventitial fibroblast extracellular matrix production in the aorta.

Takayasu arteritis (TAK) is a chronic large vessel disease characterized by aortic fibrotic thickening, which was mainly mediated by activation of aorta adventitial fibroblasts (AAFs). Our previous genetic study demonstrated that TAK-associated locus IL6 rs2069837 regulated glycoprotein non-metastatic melanoma protein B (GPNMB) expression. Thus, this study aimed to investigate the pathogenic role of GPNMB in TAK. Through pathological staining, we find that GPNMB was mainly expressed in vascular adventitia and positively correlated with adventitial extracellular matrix (ECM) expression in TAK vascular lesion. Specifically, GPNMB was increased in adventitial CD68+ macrophages, which were closely located with CD90+ adventitial fibroblasts. In in-vitro cell culture, THP-1-derived macrophages with GPNMB overexpression promoted ECM expression in AAFs. This effect was also confirmed in aortic tissue or AAFs culture with GPNMB overexpression or active GPNMB protein stimulation. Mechanistically, Co-IP assay and siRNA or inhibitor intervention demonstrated that integrin αVß1 receptor mediated GPNMB effect on AAFs, which also activated downstream Akt and Erk pathway in AAFs. Furthermore, we showed that leflunomide treatment inhibited GPNMB-mediated fibrosis in AAFs, as well as GPNMB expression in macrophages, which were also partially validated in leflunomide-treated patients. Taken together, these data indicated that macrophage-derived GPNMB promotes AAFs ECM expression via the integrin αVß1 receptor and Akt/Erk signaling pathway and leflunomide might play an anti-fibrotic role in TAK by interfering with the macrophage-derived GPNMB/AAFs axis. This study provides evidence that targeting GPNMB is a potential therapeutic strategy for treating vascular fibrosis in TAK.

Inflammatory Diseases of the Aorta: JACC Focus Seminar, Part 2.

Inflammatory aortitis is most often caused by large vessel vasculitis (LVV), including giant cell arteritis, Takayasu's arteritis, immunoglobulin G4-related aortitis, and isolated aortitis. There are distinct differences in the clinical presentation, imaging findings, and natural history of LVV that are important for the cardiovascular provider to know. If possible, histopathologic specimens should be obtained to aide in accurate diagnosis and management of LVV. In most cases, corticosteroids are utilized in the acute phase, with the addition of steroid-sparing agents to achieve disease remission while sparing corticosteroid toxic effects. Endovascular and surgical procedures have been described with success but should be delayed until disease control is achieved whenever possible. Long-term management should include regular follow-up with rheumatology and surveillance imaging for sequelae of LVV.

Clinical features and risk factors of intracranial artery disease in patients with Takayasu arteritis.

OBJECTIVES: It has been known that aorta, subclavian, and extracranial arteries are commonly involved in Takayasu arteritis (TA). However, the involvement of intracranial artery in TA has not been well explored. The purpose of this study was to describe the clinical characteristics of intracranial artery lesions in TA patients and identify associated risk factors. METHODS: A total of 160 patients diagnosed with TA at Beijing Anzhen Hospital from November 2012 to November 2019 were retrospectively enrolled in this study and assigned to different groups according to the presence or absence of intracranial artery lesions. RESULTS: Our data showed that 20% of the enrolled 160 patients developed intracranial artery lesions and the right internal carotid artery (ICA) was the most common involved artery (53%). The average age of patients with intracranial artery lesions was significantly older compared to that of patients without intracranial artery involvement (43.56 ± 11.40 vs 36.41 ± 12.22, p = 0.003). In addition, more patients in the intracranial artery group had concomitant disease histories of stroke and/or hypertension (p = 0.010, 0.033). Chest tightness, chest pain, palpitation, coronary artery lesions, and extracranial segment lesions of ICA were more commonly observed in patients with intracranial artery lesions (p < 0.001, 0.017, 0.015, < 0.001, 0.003). Furthermore, we discovered that patients with coronary artery involvement, extracranial segment lesions of ICA, and higher Vasculitis Damage Index (VDI) score had an increased risk of developing intracranial artery lesions (p = 0.013, 0.019, 0.019). CONCLUSION: Our study showed that the intracranial artery disease was common in TA and was associated with coronary artery lesions, extracranial segment lesions of ICA, and higher VDI score. Key Points • Intracranial artery disease in TA patients had advanced age and higher triglyceride level. • Besides coronary artery lesions, intracranial artery disease in TA patients was associated with the extracranial segment lesions of ICA and higher VDI score.

Comparison of Different Thoracic Aortic Wall Characteristics for Assessment of Disease Activity in Takayasu Arteritis: A Quantitative Study with 3.0 T Magnetic Resonance Imaging.

BACKGROUND: Determination of disease activity in Takayasu arteritis (TAK) is crucial for clinical management but challenging. The value of different magnetic resonance imaging (MRI) characteristics for the assessment of disease activity remains unclear. This study investigated the imaging findings of the thoracic aortic wall and elasticity by using a comprehensive 3.0 T MRI protocol. METHODS: We prospectively enrolled 52 consecutive TAK patients. TAK activity was recorded according to the ITAS2010. All the patients underwent thoracic aortic MRI. The luminal morphology of the thoracic aorta and its main branches were quantitatively evaluated using a contrast-enhanced magnetic resonance angiography (MRA) sequence. The maximum wall thickness of the thoracic aorta, postcontrast enhancement ratio, and aortic wall edema were analyzed in each patient through pre- and post-enhanced T1-weighted and T2-weighted imaging. Pulse-wave velocity (PWV) of the thoracic aorta was calculated using a four-dimensional flow technique. RESULTS: The majority of the 52 patients had type V disease (34.62%, 18/52). Among all the MRI indicators of the thoracic aorta, the area under the curve was the largest for the maximal wall thickness (0.804, 95% confidence interval [CI] = 0.667-0.941). The maximal wall thickness (93.33%, 95% CI = 68.1%-99.8%) exhibited the highest sensitivity with a cutoff value of 3.12 mm. Wall edema (84.00%, 95% CI = 63.9%-95.5%) presented the highest specificity. A positive correlation was noted between PWV and patients' age (r = 0.54, p < 0.001), disease duration (r = 0.52, p < 0.001), and the maximum wall thickness (r = 0.45, p = 0.001). CONCLUSIONS: MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. Aortic maximal wall thickness was the most accurate indicator of TAK activity. The early phase was superior to the delay phase for aortic wall enhancement analysis for assessing TAK activity.

Development of severe colitis in Takayasu arteritis treated with tocilizumab.

Relapse of Takayasu arteritis (TAK) is frequent, and the use of biologics is required in refractory cases. Tocilizumab (TCZ), a biological agent used in TAK, is known to increase the incidence of diverticulitis in patients with rheumatoid arthritis. Adverse events of TCZ in TAK have been poorly recognised. This study aimed to investigate the occurrence of severe colitis among patients with TAK receiving TCZ. We enrolled 116 patients with TAK who met the criteria of the American College of Rheumatology and visited our department between 2018 and 2020. The occurrence of severe colitis and its clinical characteristics were retrospectively evaluated. TCZ was introduced in 34 of 116 patients (29.3%). Severe colitis that required hospitalisation was observed in three of the 34 patients receiving TCZ (8.8%). All patients were female and had Numano type V artery lesions, and the ascending colon was commonly affected. Wide lesions that reached the sigmoid colon, colonic perforation, bacteraemia, or positive stool cultures were observed in some patients. All patients received antibiotics and intestinal rest, and TCZ was resumed in one patient. IL-6 plays a physiological role in the intestine, including recovery from ischaemic damage. In addition to infectious aetiology, blocking the physiological roles of IL-6 by TCZ is considered important for the development of colitis in TAK. Severe colitis is an important adverse event in patients with TAK who receive TCZ. The risk of bloodstream infection associated with colitis should be recognised, especially in patients who have undergone vascular surgery. Key Points • Severe colitis was observed in 8.8% of patients with TAK receiving tocilizumab • Patients had type V artery lesions and ascending colon involvement and were under long-term use of corticosteroids • Inhibition of the physiological roles of IL-6 in the intestinal tract might also be involved.

Takayasu's Arteritis: A Case Report.

Takayasu's arteritis is a chronic vasculitis of medium and large vessels. The most involved vessel is the aorta and its major branches. The disease is primarily seen in young women. The described incidence of the disease ranges from 0.3 to 3.3 million per year. The vessels are characterized by mononuclear infiltration and granulomatous inflammation of vascular media, which leads to arterial wall thickening with stenosis, occlusion, and aneurysmal dilation. Here we present a case of Takayasu's arteritis in a 26-year-old woman who presented with syncope and dizziness with thickened walls of the arch of the aorta and its branches in Magnetic Resonance Imaging angiogram finding. Women of Japanese descent are not the only ones who can develop Takayasu's arteritis; it can affect anyone. Therefore, early diagnosis and treatment are warranted. When the disease is dormant, the outcome seems favourable. Keywords: aortitis syndrome; arteritis; case reports; pulseless disease; young female arteritis.

Takayasu arteritis in an adolescent with Crohn's disease.

Crohn's disease (CD) and Takayasu arteritis (TA) are two distinct clinical entities. Τhe likelihood of both diseases coexisting is low, and although CD co-occurs with all types of vasculitis, TA is the most common subtype. Herein, the case of a 15-year-old female, diagnosed with TA following an initial diagnosis of CD, is reported. A review of the literature, including a systemic review of the case reports and case series of children and adolescents up to the age of 21, with both CD and TA, follows the case description. In total, 28 cases of TA and CD were retrieved. The median age of patients was 14.8 years, they were mostly females (72%) and the median time between the two diagnoses was 3.7 years. In the majority of cases, CD was diagnosed first and TA followed. Computed tomography angiography and magnetic resonance angiography were the preferred imaging modalities to assist diagnosis.

Spinal Hypertrophic Pachymeningitis Causing Thoracic Myelopathy in a Patient of Takayasu Arteritis: A Case Report.

CASE: A 52-year-old man presented with thoracic myelopathy, and his magnetic resonance imaging (MRI) was suggestive of T1-T4 hypertrophic-pachymeningitis. Incidentally, circumferential thickening of the infra-renal abdominal aorta and right common iliac artery was seen, which along with the findings in a contrast computed tomography was consistent with Takayasu arteritis (TA). The patient underwent T1-T4 laminectomy, thinning of dura, biopsy, and steroid therapy. At the 1-year follow-up, he was asymptomatic and MRI revealed resolution of the lesion. CONCLUSION: This is the first report describing an association between TA and hypertrophic spinal pachymeningitis, emphasizing the unusual neurological manifestation of myelopathy and complete resolution of symptoms with timely and appropriate intervention.

Assessment of Low Bone Mineral Density in Untreated Patients with Takayasu's Arteritis.

Chronic inflammation affects bone metabolism and accelerates bone loss. This study is aimed at analyzing the prevalence of low bone mineral density (LBMD) in patients with untreated Takayasu's arteritis (TA) and risk factors. Forty untreated TA patients were enrolled, including 38 premenopausal women and 2 men before 50 years old. The control group included 60 age- and gender-matched healthy persons. Bone mineral density (BMD) of lumbar vertebrae and hip in patients with TA and the control group was measured by the dual-energy X-ray method. Serum 25OHD and ß-CTX were also measured. The lumbar BMD of TA patients (0.89 ± 0.11 g/cm2) was significantly lower than that of the healthy control (0.97 ± 0.11 g/cm2). The prevalence of LBMD at the lumbar spine (17.50%) was significantly higher than that of the control group (3.33%). However, there was no significant difference at the hip. The 25OHD of TA patients was lower than that of healthy controls, while the level of ß-CTX was higher. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with LBMD were higher than those in patients with normal BMD. According to univariate correlation analysis, there was a significant negative correlation between LDL-C and lumbar BMD. Binary logistic regression analysis showed that LDL-C was an important factor affecting the occurrence of LBMD in patients with TA (OR = 25.269, P = 0.02). Our result reveals bone loss in TA patients, which hints the relationship among inflammation, lipid metabolism, and bone metabolism.

A susceptibility locus in the IL12B but not LILRA3 region is associated with vascular damage in Takayasu arteritis.

HLA-B*52 is an established genetic factor in Takayasu arteritis (TAK). Recently, single nucleotide polymorphisms (SNPs) in IL12B (rs6871626) and LILRA3 (rs103294) were newly identified as non-HLA susceptibility loci in TAK. Here, we examined how these SNPs contribute to clinical characteristics and vascular damage in TAK. We retrospectively reviewed the medical records of 99 TAK patients enrolled in our previous genome-wide association study, and whose genotypes for IL12B rs6871626, LILRA3 rs103294, and HLA-B*52 were available. Incidence of aortic regurgitation (AR) was significantly associated with the A allele (risk allele) of IL12B rs6871626 (CC 42%, AC 61%, AA 81%; p = 0.0052; odds ratio [OR] 2.45), as well as with the incidence of hypertension (p = 0.049; OR 1.82) and the proportion of patients who underwent aortic valve replacement (p = 0.023; OR 3.64). Regarding vascular damage, there was positive correlation between the Takayasu Arteritis Damage Score and the A allele of IL12B rs6871626 (CC 3.42 ± 2.71, AC 4.06 ± 3.25, AA 6.00 ± 2.81; p = 0.0035; ß = 1.35) and between the Vasculitis Damage Index and the A allele (CC 3.47 ± 1.98, AC 4.33 ± 2.40, AA 5.37 ± 2.22; p = 0.0054; ß = 0.96). Contrarily, no correlation was found between LILRA3 rs103294 and vascular damage. In the present study, IL12B rs6871626 was associated with vascular damage in TAK, whereas LILRA3 rs103294 was not. Genotyping of IL12B rs6871626 may help to identify patients at risk of disease progression.