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

Wang, Kaiwen; Zhao, Jiangfeng; Chen, Zhiwei; Li, Ting; Tan, Xiaoming; Zheng, Yu; Gu, Liyang; Guo, Li; Sun, Fangfang; Wang, Haiting; Li, Jiajie; Wang, Xiaodong; Riemekasten, Gabriela; Ye, Shuang

doi:10.1093/rheumatology/key341

Cited by 38 publications

(25 citation statements)

References 36 publications

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“…CD19 + B cell counts were also lower in CMV + patients than in CMV − participants (91.5 cells/µL, IQR 51.3-147.8 cells/µL vs. 159.35 cells/µL, IQR 83.5-253.8 cells/µL, p = 0.113) although the difference was not statistically significant. This is consistent with a recent report that CD4 + CXCR4 + T cells were associated with the severity of MDA5 + DM-ILD and mortality in a study in which high-resolution computed tomography scores and pulmonary functions (forced vital capacity and diffusion capacity of the lung for carbon monoxide) were evaluated (24). In recent studies, circulating CD28-null T cells were also significantly higher in CMV + DM patients, in whom CD28-null T cells may accelerate inflammation in muscle (25).…”

Section: Discussionsupporting

confidence: 92%

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study

et al. 2021

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Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p < 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p < 0.05).Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.

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Section: Discussionsupporting

confidence: 92%

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study

et al. 2021

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“…CD4 + T cells are critical for the development of interstitial pneumonitis followed by rheumatoid arthritis (28). An increased specific CD4 + T cell subtype (CD4+CXCR4+ T cell) was significantly associated with the severity and mortality of idiopathic inflammatory myopathy-associated interstitial lung disease (29). Mycoplasma pneumoniae immunized or P1 protein immunized mice had significantly increased CD4 + T cells and CD4 + /CD8 + ratio in spleen cells (30).…”

Section: Discussionmentioning

confidence: 99%

Immunological Features of Pediatric Interstitial Pneumonia Due to Mycoplasma pneumoniae

Sheng

Yang

et al. 2021

Front. Pediatr.

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Background: Inflammatory response, oxidative stress, and immunologic mechanism are involved in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). However, the role of immune system of pediatric interstitial pneumonia due to M. pneumoniae infections remains poorly understood. The aim of this study was to analyze the immunologic features of pediatric interstitial pneumonia due to Mycoplasma pneumoniae (M. pneumoniae).Methods: A retrospective study was conducted on a primary cohort of children with MPP. Propensity score analysis was performed to match interstitial pneumonia and pulmonary consolidation children.Results: The clinical characteristics strongly associated with the development of interstitial pneumonia were boys, age >5 years, wheezing history, hydrothorax free, lymphocytes (>3.0 × 109/L), CD19+ (>0.9 × 109/L), CD3+ (>2.5 × 109/L), CD4+ (>1.5 × 109/L), CD8+ (>0.9 × 109/L), interleukin-6 (IL-6, <30 pg/ml), IL-10 (<6 pg/ml), and interferon-γ (IFN-γ, <15 pg/ml). After propensity score analysis, children with interstitial pneumonia showed significantly higher CD19+, CD3+, and CD4+ T cell counts, and lower serum IL-6, IL-10, and IFN-γ levels. The final regression model showed that only CD4+ T cells (>1.5 × 109/L, OR = 2.473), IFN-γ (<15 pg/ml, OR = 2.250), and hydrothorax free (OR = 14.454) were correlated with the development of interstitial pneumonia among children with MPP.Conclusions: The M. pneumoniae-induced interstitial pneumonia showed increased CD4+ T cells and lower serum IFN-γ level. Specific immunologic profiles could be involved in the development of pediatric interstitial pneumonia due to M. pneumoniae infections.

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“…[ 4 , 5 ] It has also been suggested that TOF may suppress T cell-derived pro-inflammatory and fibrosis-promoting effects in vitro, and is expected to have a therapeutic effect on intractable ILD associated with cADM. [ 7 ] It is suggested that interferon-gamma (IFN-γ) is deeply involved in the etiology of life-threatening DM with ILD, and TOF, which has an effect of suppressing IFN-γ production from T cells, may be effective for refractory DM with ILD. [ 8 , 9 ] In cases such as that presented here, in which readministration of CY is difficult due to adverse events, or in recurrent cases with high levels of pulmonary fibrosing markers such as KL-6, TOF administration might be a useful therapeutic option.…”

Section: Discussionmentioning

confidence: 99%

Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission

Ishikawa¹,

Kasuya²,

Fujiwara³

et al. 2020

Medicine

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Rationale: Antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive clinically amyopathic dermatomyositis (cADM) is frequently complicated with interstitial lung disease (ILD) and has a poor prognosis. Although the short-term prognosis of anti-MDA5 Ab-positive cADM is poor, it has been suggested that the recurrence rate is not higher than that of anti-MDA5 Ab-negative dermatomyositis. Combination therapy with corticosteroids, calcineurin inhibitors, and cyclophosphamide is the gold standard for the remission induction therapy at the onset. Recently, it has been reported that tofacitinib (TOF) could be effective for refractory anti-MDA5 Ab-positive cADM with ILD. Although initial remission induction therapy has been established, therapeutic strategies for relapse cases have not yet been established. Patient concerns: A 57-year-old woman who was diagnosed with anti-MDA5 Ab-positive cADM complicated with ILD. In October 2016, she was treated with prednisolone (PSL), tacrolimus (TAC), and cyclophosphamide (CY). These treatments were successful, and PSL could be tapered. However, she developed strong nausea and general fatigue as adverse events of CY. In April 2018, PSL was discontinued, and maintenance therapy was given with TAC. In July 2018, Gottron's sign and ILD recurred. Skin lesions on the finger were partially ulcerated and ILD was also worsening. We proposed a remission reinduction therapy including CY. However, she was rejected CY from experience with past adverse event of CY. Diagnosis: Based on skin lesions and chest computed tomography (CT) findings, the diagnosis was a recurrence of anti-MDA5 Ab-positive cADM with ILD. Interventions: Treatment by TOF 10 mg and PSL 22.5 mg (0.5 mg/kg equivalent) was introduced in November 2018. Outcomes: After introducing TOF and PSL, her skin lesions and chest CT findings of ILD gradually improved. Six months after the induction of TOF, the skin ulcer was epithelialized. One year after the introduction of TOF, PSL was decreased to 9 mg, and the disease activity did not re-exacerbate. Lessons: This case report is the first report suggesting the effectiveness of TOF for recurrent case of anti-MDA5 Ab-positive cADM with ILD. TOF might be an effective therapeutic option for treating recurrent case of anti-MDA5 Ab-positive cADM.

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

Cited by 38 publications

References 36 publications

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study

Immunological Features of Pediatric Interstitial Pneumonia Due to Mycoplasma pneumoniae

Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission

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