[A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies].

OBJECTIVE: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment. METHODS: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs. RESULTS: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever (P=0.002) and rapid progressive interstitial lung disease (RP-ILD) (P=0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype (P=0.007), interstitial lung disease (ILD) (P=0.001), eleva-ted AST (P=0.012), elevated serum ferritin (P=0.016) and decreased count of CD4+T cells in peripheral blood (P=0.004) might be the risk factors for IIMs non-complete clinical response. CONCLUSION: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Clinical and immunological characteristics and prognosis of patients with autoantibody negative dermatomyositis: a case control study.

OBJECTIVES: Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM) clinical phenotypes. The aim of this study is to explicate the clinical and immunological features of MSAs-negative DM patients. METHODS: A total of 515 individuals diagnosed with DM was screened from 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed. RESULTS: MSAs-negative DM patients were categorized into two groups: MAAs-negative (MSAs (-)/MAAs (-)) group and MAAs-positive (MSAs (-)/MAAs (+)) group. The percentage of Raynaud's phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positive DM patients and MSAs (-)/MAAs (-) DM patients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumonia and usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among total CD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onset age, higher level of carcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients. CONCLUSIONS: Compared with MSAs-positive group, MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DM patients:   • The MSAs (-)/MAAs (+) DM patients demonstrated a higher prevalence of organizing pneumonia (OP) and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid.   • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients.   • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negative patients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients.   • MSAs-negative DM patients had a more favorable prognosis than MSAs-positive DM patients. A multivariable regression analysis revealed the advanced onset age, high CEA levels, and RP-ILD were risk factors for mortality in DM patients.

Respiratory infection risk in primary Sjögren's syndrome complicated with interstitial lung disease: a retrospective study.

OBJECTIVES: To explore clinical and laboratory characteristics of primary Sjögren's syndrome (pSS) complicated with interstitial lung disease (ILD) and investigate the risk factors for respiratory infections in pSS-ILD. METHODS: A cohort of 162 pSS-ILD patients in Peking University People's Hospital from 2015 to 2020 were included, and all medical records were completely collected. We screened 53 patients suffering from respiratory infections as study cases, compared with 109 age- and sex-matched controls. Differences between infection group and control group were compared. Univariate and multivariate binary logistic regression tests were conducted to identify potential risk factors for respiratory infections in pSS-ILD patients. RESULTS: Among 162 pSS-ILD patients, 32.72% (53/162) suffered from respiratory infections. The most frequent type of ILD was nonspecific interstitial pneumonia (32.08%, 51/159), and the most common type of pathogen was bacteria (64.25%, 34/53). Infection group showed higher levels of ESSDAI (P < 0.001), CRP (P < 0.001), ESR (P = 0.003), and C3 (P = 0.020) but lower level of DLCO-SB (P = 0.015). Univariate logistic model revealed that PAH and the use of glucocorticoid increased infection risk in pSS-ILD patients. On multivariate logistic regression analysis, PAH (OR = 3.993, 95% CI = 1.192-13.373, P = 0.025) and severe reduction of DLCO (DLCO-SB < 40%, OR = 4.625, 95% CI = 1.281-16.702, P = 0.019) were significantly associated with increased risk of respiratory infections in pSS-ILD patients. CONCLUSION: Among pSS-ILD patients, the most frequent type of ILD was nonspecific interstitial pneumonia. In patients with infection, bacteria were the most common pathogen. Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risk. PAH and reduction of DLCO were identified as independent risk factors. Key Points • ILD and infectious diseases severely affect pSS patient conditions. • Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risks in pSS-ILD. • PAH and reduction of DLCO were identified as independent risk factors for lower respiratory infection.

Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus.

INTRODUCTION: Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action. METHODS: A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured. RESULTS: After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend. CONCLUSION: Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

Low-dose IL-2 could decrease the levels of TG-Ab and TPO-Ab in AITD with concurrent SLE patients.Low-dose IL-2 may regulate Treg/Tfh balance and B-cells to ameliorate TG-Ab and TPO-Ab.Low-dose IL-2 provides a new avenue for AITD clinical treatment.

Predictors and prognostic stratification for lupus low disease activity state: results from a prospective clinical trial.

OBJECTIVE: To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. METHOD: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. RESULTS: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the three risk groups based on the identified risk factors. CONCLUSION: Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Sequence characteristics and phylogenetic analysis of H9N2 subtype avian influenza A viruses detected from poultry and the environment in China, 2018.

H9N2 subtype avian influenza A virus (AIV) is a causative agent that poses serious threats to both the poultry industry and global public health. In this study, we performed active surveillance to identify H9N2 AIVs from poultry (chicken, duck, and goose) and the environment of different regions in China, and we phylogenetically characterized the sequences. AIV subtype-specific reverse transcription polymerase chain reaction (RT-PCR) showed that 5.43% (83/1529) samples were AIV positive, and 87.02% (67/77) of which were H9N2 AIVs. Phylogenetic analysis revealed that all H9N2 field viruses belonged to the Y280-like lineage, exhibiting 93.9-100% and 94.6-100% of homology in the hemagglutinin (HA) gene and 94.4-100% and 96.3-100% in the neuraminidase (NA) gene, at the nucleotide (nt) and amino acid (aa) levels, respectively. All field viruses shared relatively lower identities with vaccine strains, ranging from 89.4% to 97.7%. The aa sequence at the cleavage site (aa 333-340) in HA of all the isolated H9N2 AIVs was PSRSSRG/L, which is a characteristic of low pathogenic avian influenza virus (LPAIV). Notably, all the H9N2 field viruses harbored eight glycosylation sites, whereas a glycosylation site 218 NRT was missing and a new site 313 NCS was inserted. All field viruses had NGLMR as their receptor binding sites (RBS) at aa position 224-229, showing high conservation with many recently-isolated H9N2 strains. All H9N2 field isolates at position 226 had the aa Leucine (L), indicating their ability to bind to sialic acid (SA) α, a 2-6 receptor of mammals that poses the potential risk of transmission to humans. Our results suggest that H9N2 AIVs circulating in poultry populations that have genetic variation and the potential of infecting mammalian species are of great significance when monitoring H9N2 AIVs in China.