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Efficacy and safety of low dose Mycophenolate mofetil treatment for immunoglobulin G4-related disease: a randomized clinical trial

期刊: RHEUMATOLOGY, 2019; 58 (1)

Objectives. This randomized, controlled clinical trial aims to compare the efficacy and safety of glucocorticoid combined with MMF and glucocorticoid monotherapy for patients with IgG4-related disease. Methods. Sixty-nine patients newly diagnosed with IgG4-related disease were randomly divided into two groups (35 patients in Group I and 34 patients in Group II). Patients in Group I received glucocorticoid monotherapy (0.6-0.8 mg/(kg.day) and tapered gradually); patients in Group II received glucocorticoid combined with MMF therapy (1-1.5 g/day). All the patients were followed up at 1, 3, 6 and 12 months. The primary endpoint was response rate in 12 months and the secondary endpoints were relapse, remission rate and adverse reactions. Results. Group I and Group II shared almost the same efficacy at the 1 month treatment, but during the follow-up, the complete response rate in Group II was much higher than that in Group I at different time points, and the cumulative relapse rate during 1 year of therapy was much higher in Group I than that in Group 11 (4000 vs 20.59%). The remission rate was lower in Group I (51.42 vs 76.47%). Relapses were more likely to happen in lung, lacrimal gland, salivary gland, paranasal sinus and kidney. MMF could reduce relapse, especially organs recurrence. No serious adverse reactions occurred in the two groups. Conclusion. Combination treatment with glucocorticoid and MMF was more effective than the monotherapy, and the relapse of IgG4-related disease might be associated with the elevated levels of serum IgG4 and the low glucocorticoid maintenance dose.

IF:5.15

Metabolic profiling of human plasma reveals the activation of 5-lipoxygenase in the acute attack of gouty arthritis

期刊: RHEUMATOLOGY, 2019; 58 (2)

Objective. Monosodium urate-induced inflammation plays a vital role in acute gout (AG). Inflammation is a multi-stage process involved in the acute release of arachidonic acid and its metabolites. However, the function of the metabolism of arachidonic acid and other polyunsaturated fatty acids in AG is not well understood. This study aimed to investigate the modification of polyunsaturated fatty acid metabolism by AG. Methods. Plasma samples from patients with an AG attack (n = 26) and gender- matched healthy controls (n = 26) were analysed by metabolic profiling of polyunsaturated fatty acids. The findings were further validated with a second cohort (n = 20 each group). The associated mechanisms were investigated in whole blood cells from the second cohort and neutrophils in vitro. Results. Plasma metabolic profiling revealed a significant increase in leukotriene B-4 (LTB4) for AG patients in both cohorts. The increase in plasma LTB4 was accounted for by the dynamic balance between the activation of 5-lipoxygenase and CYP4F3, the former mediating the biosynthesis of LTB4 and the latter mediating its metabolism. This was supported by significantly increased transcriptional levels of 5-lipoxygenase and CYP4F3 in whole blood cells from AG patients compared with those of controls, and the uric acid-caused dose-relevant and time-dependent activation of 5-lipoxygenase and CYP4F3 at the transcriptional and molecular levels in vitro. Conclusion. Increased LTB4 in AG patients is mainly due to activation of 5-lipoxygenase. 5-Lipoxygenase inhibition may be of therapeutic value clinically.

IF:5.15

CD4(+)CXCR4(+) T cells as a novel prognostic biomarker in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

期刊: RHEUMATOLOGY, 2019; 58 (3)

Background. There is an unmet need for the development of new biomarkers for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Methods. Peripheral CD4(+)CXCR4(+) T cells, stromal cell-derived factor-1 and Krebs von den Lungen-6 were measured in patients with IIM-ILD (n=85) and controls. The relation to pulmonary functions, high-resolution CT scores, specific clinical phenotypes and survival was analysed. Cytokine-expression profiling of these CD4(+)CXCR4(+) T cells and their co-culture with pulmonary fibroblasts were conducted. Results. The peripheral percentages of CD4(+)CXCR4(+) T cells were significantly elevated in IIM-ILD patients, and correlated with high-resolution CT score (r= 0.7136, P < 0.0001) and pulmonary function impairments, such as percentage of forced volume vital capacity (r= -0.4734, P = 0.0005). They were associated with anti-melanoma differentiation-associated gene 5 autoantibodies and the amyopathic DM phenotype. In IIM-ILD, peripheral percentages of CD4(+)CXCR4(+) T cells >= 30% revealed a 6-month mortality as high as 47%. These CD4(+)CXCR4(+) T cells express high levels of IL-21 and IL-6. In vitro blockade of IL-21 signalling by neutralization of IL-21 or Janus kinase inhibitor could abolished the fibroblast proliferation. Conclusion. Overall, peripheral CD4(+)CXCR4(+) T cells appear to be a potentially valuable novel biomarker associated with the severity and prognosis of IIM-ILD. They promote pulmonary fibroblast proliferation via IL-21, which may herald future targeted treatments for this severe disease.

IF:5.15

Comparison of two subsets of Chinese patients with retroperitoneal fibrosis in terms of IgG4 immunohistochemical staining

期刊: RHEUMATOLOGY, 2019; 58 (3)

Objective. To identify clinical and pathological differences between IgG4-related retroperitoneal fibrosis (IgG4-RPF) and idiopathic RPF (iRPF) in a Chinese population. Method. Clinical and pathological data of 50 RPF patients from 2006 to 2016 were retrospectively analysed. The presence of at least one characteristic histopathological feature, >30 IgG4(+) plasma cells per high power field, and an IgG4(+)/IgG(+) plasma cells ratio cutoff of >40% were used to define IgG4-RPF. Results. Patients with IgG4-RPF were significantly more likely to have pain (94.1 vs 68.8%, P=0.048), elevated serum IgE concentration (166.1 vs 40.2 IU/ml, P=0.029) and tissue eosinophilia (47.1 vs 12.5%, P= 0.018), compared with patients with iRPF. In the IgG4-RPF subgroup, patients with tissue eosinophilia demonstrated higher levels of CRP (4.3 vs 1.9 mg/di, P= 0.027) and ESR (62.1 vs 22.8 mm/h, P = 0.001). Among the 50 patients with RPF, the average number of tissue IgG4 plasma cells was positively correlated with the number of tissue eosinophils (r= 0.37, P = 0.009). Moreover, serum IgG4 concentration and serum IgE concentration showed positive correlation (r= 0.834, P = 0.000). Conclusion. The distinct serological and histopathological features of Chinese patients with IgG4-RPF were elevated serum IgE concentration and tissue eosinophilia, which potentially can aid and support the diagnosis. As serum IgG4 concentration may be normal in patients with IgG4-RPF, serum IgE may represent a useful serological marker in distinguishing IgG4-RPF from iRPF.

IF:5.15

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