Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease.

OBJECTIVES: The aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD. METHODS: We performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results. RESULTS: We identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD. TOP2A_B cells and TOP2A_T cells had stemness signatures, and trajectory analysis showed that TOP2A_B cells may differentiate into IgG4+plasma cells and that TOP2A_T cells may differentiate into T follicular helper (Tfh) cells. ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD. CONCLUSION: Our data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

Dynamic Metastable Characteristics of Carbon Cages Embedded with Er2C2.

Novel endohedral metallofullerenes (EMFs), namely, Er2C2@C2v(5)-C80, Er2C2@Cs(6)-C82, Er2C2@Cs(15)-C84, Er2C2@C2v(9)-C86, Er2C2@Cs(15)-C86, and Er2C2@Cs(32)-C88, had been experimentally synthesized, and the unique structures and many fascinating properties had also been widely explored. Nevertheless, the position of the Er atoms inside the cage shows a severe disorder within the stable EMF monomer, which is difficult to understand and explain from the experimental point of view. In this work, based on the density functional theoretical calculations, the Er2C2@Cs(6)-C82 has 73 directional isomers and 2 Er atoms that are far beyond from Er-Er single bonding and tend to be close to the cage side (marked as "shell"), and the core (Er2C2 units) takes on a butterfly shape as generally revealed. The energy difference between any two of the isomers is in the range of 0.05 to 25.6 kcal/mol, indicating a relatively easy thermodynamic transition between the isomers. The other five Er carbide cluster EMFs (Er2C2@C2v(5)-C80, Er2C2@Cs(15)-C84, Er2C2@C2v(9)-C86, Er2C2@Cs(15)-C86, and Er2C2@Cs(32)-C88) are also studied in the same way, and 30, 37, 39, and 43 most stable Er-oriented sites inside the cage, respectively, are obtained. In addition, the shape of the Er2C2 gradually changed from butterfly to linear. Moreover, the electronic structure and molecular orbital analyses show that it is easy for Er2C2@C80-88 to form a charge transfer state of [Er2C2]4+@[C80-88]4- via the dynamic core-shell coordination equilibrium. Er2C2 with a steep drop in chemical stability is restricted to forming varying degrees of metastable states in the shell, determined by the shell size, to ensure the overall stability. The lowest unoccupied molecular orbital energy level of these EMFs is increased by 0.5-1.1 eV compared with fullerenes C80-88, potentially providing favorable conditions for suitable energy level matching with EMF as an electron acceptor used in organic solar cell devices.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome.

BACKGROUND: ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. METHODS: Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. RESULTS: A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). CONCLUSION: APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China.

OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. METHODS: This retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. RESULTS: The results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35-22.64) and 22.31 (4.32-115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. CONCLUSIONS: Anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Analysis of the clinical features of antisynthetase syndrome: a retrospective cohort study in China.

OBJECTIVE: To summarize the clinical, serological, and radiological characteristics of anti-synthetase syndrome (ASS) patients with different anti-aminoacyl-tRNA synthase antibody. METHODS: Retrospective analysis was performed based on the clinical data of 88 patients diagnosed with ASS in Tianjin Medical University General Hospital from January 2015 to December 2020. The clinical data included general conditions, serological indexes, high-resolution CT (HRCT) characteristics, and pulmonary function manifestations. RESULTS: Among the 88 patients, there were 17 males and 71 females. The anti-synthetase antibodies included anti-Jo-1 (n = 42), anti-PL-7 (n = 14), anti-PL-12 (n = 9), anti-EJ (n = 20), and anti-OJ (n = 3) antibodies. The most common clinical manifestations of ASS patients were interstitial lung disease (ILD) (90%, 79/88), followed by myositis (79.5%, 70/88), arthritis (50%, 44/88), and rash (50%, 44/88). The frequency of arthritis in the anti-Jo-1 antibody-positive group was higher than that of the anti-PL-7 and anti-EJ antibody groups (P = 0.004, P = 0.002, respectively). The frequency of Gottron's sign in the anti-PL-7 antibody positive group was higher than that of the anti-Jo-1 and anti-PL-12 antibody-positive groups (P = 0.006, P = 0.04). Isolated arthritis was the most frequent initial symptoms in anti-Jo-1 antibody-positive group (47.6%, 20/42), while isolated ILD was most frequent in patients with anti-EJ antibody (50%, 10/20), and isolated myositis in patients carrying anti-OJ (66.7%, 2/3). There were only 32 cases (36.4%) with the typical clinical triad (myositis, arthritis, ILD). In our cohort, 79 patients (90%) were complicated with ILD. Meanwhile, 7 out of 79 cases were classified into rapid progressive group with 6 cases (85.7%) carrying anti-Ro-52 antibody. The probability of reticular and honeycombing shadow in HRCT of patients with anti-EJ antibody positive was higher than that of other groups (P < 0.05). CONCLUSION: ILD, myositis, and arthritis were the most common clinical manifestations in patients with ASS. Different antibody-positive patients have different initial symptoms. Patients with isolated arthritis, myositis, and ILD should be vigilant of ASS. The complication of anti-Ro-52 antibody in ASS patients was associated with rapidly progressive pulmonary interstitial disease. Patients with positive anti-EJ antibodies tend to have ILD as the first symptom, and with high occurrence of ILD, the HRCT showed more serious patterns, suggesting the correlation between anti-EJ antibodies and ILD. Key Points • Analyzing specific clinical manifestations in ASS patients with different ARS antibodies can raise awareness of the disease and reduce misdiagnosis. • Anti-EJ antibodies were correlated with ILD. • Anti-Ro-52 antibodies may correlate with RP-ILD in ASS patients.

Predictive factors for progressive fibrosing interstitial lung disease in anti-synthetase syndrome.

OBJECTIVES: Interstitial lung disease (ILD) is common in anti-synthetase syndrome (ASS). Progressive fibrosing ILD (PF-ILD) may develop in ILD with autoimmune features. Data on PF-ILDs in ASS as a group are scarce. This study aimed to explore the characteristics and predictors of PF-ILD in ASS patients. METHODS: This retrospective study enrolled 96 ASS-ILD patients. Baseline clinical data were collected. PF-ILD assessments were conducted at every hospital visit during windows of 24 months after initial diagnosis. Phenotypic, survival features and predictors of PF-ILD were estimated through SPSS 22.0. RESULTS: The results revealed that 35.42% (34/96) were evaluated to be PF-ILD with a median interval time of 14.73 months. Nonspecific interstitial pneumonia was the most common radiological pattern of PF-ILD. Ground glass opacity (GGO), traction bronchiectasis and reticulation were representative high-resolution computed tomography findings of this group. Compared with the non-progressive group, PF-ILD patients had higher frequencies of anti-Ro-52 antibodies (91.18% vs 66.13%, P = 0.007) and GGO in the lower + middle and lower + middle + upper zones of the left lung, as well as lower + middle zones in the right lung (85.30% vs 54.84%, P = 0.003; 64.71% vs 38.71%, P = 0.015; 82.35% vs 58.06%, P = 0.016). Multivariate Cox analysis identified that anti-Ro-52 antibody (hazards ratio [HR] 3.55, 95% CI 1.06-11.90, P = 0.040) and GGO in left lower + middle lung zones (HR 22.11, 95% CI 1.95-250.90, P = 0.012) were independent risk factors for PF-ILD. CONCLUSIONS: PF-ILD was associated with poor prognosis. Over one-third of ASS-ILD patients may develop to PF-ILD. Anti-Ro-52 antibody positivity and GGO in left lower + middle lung zones were independent risk factors for PF-ILD in ASS patients.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.