Autoimmune liver disease (AILD) is a series of chronic liver diseases with abnormal immune responses, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The treatment options for AILD remain limited, and the adverse side effects of the drugs that are typically used for treatment frequently lead to a low quality of life for AILD patients. Moreover, AILD patients may have a poor prognosis, especially those with an incomplete response to first-line treatment. Mesenchymal stem cells (MSCs) are pluripotent stem cells with low immunogenicity and can be conveniently harvested. MSC-based therapy is emerging as a promising approach for treating liver diseases based on their advantageous characteristics of immunomodulation, anti-fibrosis effects, and differentiation to hepatocytes, and accumulating evidence has revealed the positive effects of MSC therapy in AILD. In this review, we first summarize the mechanisms, safety, and efficacy of MSC treatment for AILD based on work in animal and clinical studies. We also discuss the challenges of MSC therapy in clinical applications. In summary, although promising data from preclinical studies are now available, MSC therapy is currently far for being applied in clinical practice, thus developing MSC therapy in AILD is still challenging and warrants further research.

Introduction: About one-third of primary biliary cholangitis (PBC) patients do not exhibit complete response to ursodeoxycholic acid (UDCA). Some of these patients were reported to benefit from the combination therapy of fibrates and UDCA, but more clinical evidence is required. In this study, we conducted a randomized, controlled trial on the safety and efficacy of fenofibrate in the treatment of patients with PBC. Methods: Forty-eight PBC patients with incomplete response to UDCA were enrolled and randomly assigned to two groups (24 in the experiment group and 24 in the control group). For the experimental group, the patients were administered 13–15 mg/kg/day UDCA in combination with 200 mg/day fenofibrate. For the control group, the patients continued to receive UDCA at 13–15 mg/kg/day. The patients were followed up for at least 12 months. The serum levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (γ-GT), aspartate aminotransferase (AST), and other biochemical parameters were measured at 3, 6, and 12 months during the trial to assess patient conditions. Results: At 12 months, 20.8% of the patients in the experimental group had all three indexes of serum ALP, γ-GT, and total bilirubin normalized, while 0% of patients in the control group reached the primary outcome (difference, 20.8 percentage points; 95% CI, 4.6–37.0). 54.2% of the patients had normal ALP levels in the experimental group and 4.2% in the control group (difference, 50 percentage points; 95% CI, 28.5–71.5). The experimental group had greater improvement of ALP ( p < 0.001) and IgG ( p = 0.026) than the control group. The biochemical indexes of the patients in the experimental group also significantly improved during the treatment of fenofibrate. Conclusion: Addition of fenofibrate can improve biochemical indexes of PBC patients who had an incomplete response to UDCA. Reversible elevation of serum creatine and transaminases is observed in some patients. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR) as ChiCTR1800020160 (protocol available online: http://www.chictr.org.cn/showproj.aspx?proj=32443 ).

Autoimmune diseases are diseases in which the body produces an abnormal immune response to self-antigens and damages its own tissues. Programmed death-1 (PD-1) and its ligands (PD-Ls) have been discovered to be important negative regulators of the immune system, playing crucial roles in autoimmunity. We analyzed the existing scientific literature dealing with this issue. In this review, the PD-1/PD-L pathway in the genetic susceptibility to and pathogenesis of rheumatic diseases is discussed. The PD-1/PD-L pathway might be helpful for diagnosing, evaluating the disease activity of and treating rheumatic diseases. PD-1/PD-L gene polymorphisms are associated with a genetic predisposition to rheumatic disorders, which can provide reference information for diagnosis and disease activity. The conclusion of the crucial role of the PD-1/PD-L pathway in the pathogenesis of rheumatic diseases is consistent, but the details remain controversial. In some animal models, manipulating the PD-1/PD-L pathway could decrease disease severity. PD-1/PD-Ls may enable us to develop new therapeutics for patients with rheumatic diseases in the future. The PD-1/PD-L pathway plays crucial roles in rheumatic disease. More work is needed to provide a better mechanistic understanding of the PD-1/PD-L pathway and to facilitate the precise therapeutic manipulation of this pathway.

Aims: To investigate the long-term survival of patients with primary Sjögren’s syndrome (pSS) in China. Methods: Patients with pSS who fulfilled the 2002 American–European Consensus Group classification criteria were prospectively enrolled from 2004 to 2011. Their baseline clinical, laboratory, and therapeutic data were collected. The primary endpoint was all-cause death by January 2018. The standard mortality ratio (SMR) was calculated by comparing with age-matched and sex-matched mortality data of the general population. Kaplan–Meier curves were obtained by time-to-event analysis. Univariate and multivariate Cox hazards regression analyses were performed to identify risk factors for mortality. Results: A total of 1054 patients were enrolled and 834 patients were followed up for a median of 94.8 months, with 48 confirmed deaths. The total SMR was 3.63 [95% confidence interval (CI) 2.60–4.66]. The 3-, 5-, and 10-year survival rates were 98.4%, 97.5%, and 92.9%, respectively. Infection, malignancy, and respiratory failure were the top three causes of mortality. We identified male sex [hazard ratio (HR) = 3.00, 95% CI 1.23–7.31], age at diagnosis ⩾50 years of age (HR = 7.69, 95% CI 3.01–19.62), thrombocytopenia (HR = 1.93, 95% CI 1.01–3.72), and interstitial lung disease (HR = 5.96, 95% CI 2.24–15.82) as the independent prognostic factors of death. Conclusions: The mortality rates of Chinese patients with pSS are higher than those of the general population. Male patients of elder age at diagnosis complicated with thrombocytopenia and interstitial lung disease might be suggestive for poorer survival and require closer follow up.

Objectives: The aim of this study is to investigate the clinical significance of myeloperoxidase (MPO)–antineutrophil cytoplasmic antibody (ANCA) on eosinophilic granulomatosis with polyangiitis (EGPA) from a longitudinal Chinese cohort.Methods: A total of 120 patients with EGPA were consecutively enrolled and followed up. Two patients with PR3 ANCA was excluded and our analysis focused on the 118 patients with EGPA. On the basis of MPO-ANCA status, baseline clinical manifestations, treatment, and outcomes were analyzed. Logistic regression analysis was performed to analyze the independently associated factors for renal involvement.Results: ANCA positivity was observed in 24.2% of patients with EGPA. Patients with MPO-ANCA accounted for 20.8%. Patients with positive MPO-ANCA had higher levels of erythrocyte sedimentation rate (ESR), C-reactive protein, Birmingham Vasculitis Activity Score (BVAS), higher ratios of fever, myalgia, renal involvement, and biopsy-proven vasculitis. Heart manifestations and asthma were more common in patients with negative ANCA. Baseline MPO-ANCA titers positively correlated with ESR, eosinophil count, and BVAS and were higher in patients with methylprednisolone pulse. Among patients with renal involvement, patients with positive MPO-ANCA had higher proportions of female, fever, biopsy-proven vasculitis, and faster ESR; patients with negative ANCA developed more skin and cardiac involvement. MPO-ANCA positivity, male, and ear involvement were the independent factors associated with renal involvement. Intravenous cyclophosphamide and immunoglobulins were prescribed more frequently in patients with positive MPO-ANCA.Conclusion: In this cohort, patients with positive MPO-ANCA and negative ANCA displayed distinct clinical features, suggesting that MPO-ANCA might be a valuable biomarker for EGPA stratification. Baseline MPO-ANCA level correlated positively with disease activity of EGPA. MPO-ANCA was a significant independent factor associated with renal involvement.

Background: Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement. Results: CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups. Conclusions: CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.