Objective
Takayasu arteritis (TAK) is a large‐vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T ...cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK.
Methods
T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age‐ and sex‐matched healthy control subjects.
Results
We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon‐γ (IFNγ) and interleukin‐17A (IL‐17A). We demonstrated the presence of IFNγ‐, IL‐6–, and IL‐17A–producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid‐treated patients with TAK compared with steroid‐free patients with TAK (for IL‐2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL‐1 receptor, IL‐17, and IL‐23).
Conclusion
The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.
Scleritis and episcleritis Perray, L; Ungerer, L; Chazal, T ...
La revue de medecine interne,
12/2023, Letnik:
44, Številka:
12
Journal Article
Recenzirano
Scleritis and episcleritis are rare ocular inflammatory diseases but deserve to be known by internists because of their frequent association with systemic autoimmune diseases. It is important to ...distinguish them between because their prognosis, therapeutic management and potential complications are very different. Episcleritis represents a superficial ocular inflammation with usually benign visual prognosis, no complication with local treatment, and is associated with a systemic autoimmune disease in rare cases. In contrast, scleritis is a potentially serious ophthalmological condition that can threaten the visual prognosis in the absence of appropriate systemic treatment. It is associated with an underlying disease in 40-50% of cases, in particular a systemic autoimmune disease (25-35% of cases) or an infectious cause (5-10% of cases). Rheumatoid arthritis and systemic vasculitides, particularly antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, are the main autoimmune causes of scleritis and episcleritis. Scleritis can reveal the underlying autoimmune disease and requires systematic etiological investigations. Aggressive, complicated, refractory forms or those associated with a systemic autoimmune disease require glucocorticoids or even immunosuppressants, and close collaboration between ophthalmologists and internists is required. The development of biologic agents offers new effective therapeutic tools in the management of these difficult cases.
Objective
Management of nonviral cryoglobulinemia vasculitis has yet to be defined. Rituximab has emerged as a novel and promising therapeutic alternative, but data are scarce. Our objective was to ...evaluate the safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis in off‐trial real‐life patients.
Methods
Prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with rituximab in off‐label conditions, were analyzed.
Results
Twenty‐three patients received treatment with rituximab for cryoglobulinemia vasculitis. Tolerance was marked by the occurrence of side effects in almost half of the patients, including severe infections in 6 (26%) of 23, with a rate of 14.1 per 100 patient‐years. These infections occurred in a particular subset of patients ages >70 years, with essential type II mixed cryoglobulinemia and renal failure with a glomerular filtration rate of <60 ml/minute, and receiving high‐dose corticosteroids. Three of these patients died. In contrast, clinical and immunologic efficacy was noted in all evaluable patients. Clinical relapses occurred in half of the patients after a median time of 13.5 months following rituximab administration, and were more frequent in patients refractory to previous immunosuppressive therapy than in previously untreated patients.
Conclusion
Data from the AIR registry show a dramatic efficacy and a steroid‐sparing effect of rituximab, but also show the occurrence of severe infections in elderly patients with renal failure and high‐dose steroids. The role of rituximab in nonviral cryoglobulinemia vasculitis remains to be defined in well‐designed randomized controlled trials.
SARS-CoV-2 infection is more severe in patients undergoing rituximab (RTX) treatment. Humoral response to vaccination is severely impaired in patients already treated with RTX, but data on antibody ...persistence in patients initiating RTX are lacking. We evaluated the impact of RTX initiation on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with immune-mediated inflammatory diseases. We performed a retrospective, multicenter study evaluating the evolution of anti-spike antibodies and breakthrough infections after initiation of RTX in previously vaccinated patients with protective levels of anti-SARS-CoV-2 antibodies. Threshold for anti-S antibodies positivity and protection were 30 and 264 BAU/mL, respectively. We included 31 previously vaccinated patients initiating RTX (21 female, median age 57 years). At first RTX infusion, 12 (39%) patients had received 2 doses of vaccine, 15 (48%) had received 3 doses, and 4 (13%) had received 4 doses. The most frequent underlying diseases were ANCA-associated vasculitis (29%) and rheumatoid arthritis (23%). Median anti-S antibody titers at RTX initiation, 3 months, and 6 months were 1620 (589–2080), 1055 (467–2080), and 407 (186–659) BAU/mL, respectively. Overall, antibody titers waned by almost two-fold at 3 months and four-fold at 6 months. Median antibody titers were significantly higher in patients who received ≥3 doses compared to those who received only 2 doses. Three patients developed SARS-CoV-2 infection without any severe symptom. Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after RTX initiation similarly to general population. Specific monitoring is useful to anticipate prophylactic strategies.
Key Points
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Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after rituximab initiation similarly to the general population.
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The number of dose of vaccine before rituximab initiation is associated with higher antibody titers at month 3.
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Monitoring antibody levels is mandatory to initiate prophylactic strategies in this population.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to ...identify associated risk factors, and to describe its therapeutic management.
This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type.
We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 95 % CI: 1.11–10.01, p = 0.03), but not with cardiovascular risk factors (OR=0.70 95 % CI: 0.23–2.21, p = 0.60), or AAV relapse (OR=2.01 95 % CI: 0.70–5.88, p = 0.16). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %).
Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.
The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus ...(HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.
Hepatitis C virus–associated polyarteritis nodosa Saadoun, D.; Terrier, B.; Semoun, O. ...
Arthritis care & research (2010),
March 2011, 2011-Mar, 2011-03-00, 20110301, Letnik:
63, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Objective
To analyze the main characteristics and outcome of polyarteritis nodosa (PAN)–type vasculitis associated with hepatitis C virus (HCV).
Methods
We reported the characteristics and outcome of ...31 patients chronically infected with HCV who satisfied the American College of Rheumatology and Chapel Hill criteria for PAN, seen between 1990 and 2009 in a university center.
Results
Among a cohort of 161 patients with HCV‐related vasculitis, 31 (19.3%) were diagnosed as having PAN. The median age was 64.5 years (interquartile range 49.5–70.5 years), with 54.8% women. Compared with HCV‐associated mixed cryoglobulinemia (HCV‐MC) vasculitis, HCV‐PAN displayed a more severe and acute clinical presentation with more frequent fever and weight loss (P < 0.0001), severe hypertension (P = 0.0006), gastrointestinal tract involvement (P < 0.0001), severe acute sensory‐motor multifocal mononeuropathy (P < 0.0001), kidney and liver microaneurysms (P = 0.002), and increased C‐reactive protein level (P < 0.0001). Complete clinical remission of vasculitis was achieved in 79.3% of HCV‐PAN patients compared to 57.5% of HCV‐MC patients (P = 0.05). In multivariate analysis, skin involvement (odds ratio OR 2.81, 95% confidence interval 95% CI 1.27–6.33) and PAN‐type vasculitis (OR 3.01, 95% CI 1.16–8.96) were independently associated with a complete clinical response of HCV vasculitis. A glomerular filtration rate <70 ml/minute (OR 0.54, 95% CI 0.24–1.21) was negatively associated with a complete clinical response of HCV vasculitis. The 5‐year survival rate was 86% in the entire cohort, regardless of the vasculitis type.
Conclusion
HCV‐PAN accounts for 19.3% of our cohort of HCV vasculitis. HCV‐PAN displays a more severe and acute clinical presentation and a higher rate of clinical remission.
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