The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis.

Palatine tonsils are the only air-contacted lymphoid organs that constantly engage in crosstalk with commensal microorganisms and serve as the first handling sites against microbial antigens. While tonsil inflammations have been implicated in various autoimmune diseases, including rheumatoid arthritis (RA), the precise role of tonsillar microbiota in autoimmune pathogenesis remains inadequately characterized. In this study, we conducted a profiling of the tonsillar microbiota and identified a notable dysbiosis in RA patients, particularly within the Streptococcus genus. Specifically, RA patients exhibited an enrichment of pathogenic Streptococcus species, including S. pyogenes, S. dysgalactiae, and S. agalactiae. Colonization with these bacteria significantly exacerbated arthritis severity and increased autoimmune responses in collagen-induced arthritis (CIA). Furthermore, immunization with peptides derived from these pathogenic Streptococcus species directly induced experimental arthritis. Conversely, RA patients demonstrated a marked deficiency in commensal Streptococcus members, notably S. salivarius. Treatment of CIA mice with S. salivarius attenuated the progression of arthritis and downregulated autoimmune responses. These findings highlight a functional link between tonsillar microbiota and RA, shedding light on their contribution to autoimmunity.

Traditional Chinese medicine for sjögren's syndrome: a national survey of attitudes and perceptions among Chinese patients and rheumatologists.

BACKGROUND: This study explored similarities and differences among Chinese patients and rheumatologists in their attitudes towards and perceptions of traditional Chinese medicine (TCM) for Sjögren's syndrome (SS), including analyzing factors that influenced their decision making. METHODS: An anonymous questionnaire was used to conduct a multicenter survey among patients with SS at three tertiary care medical centers in Beijing and among rheumatology clinicians at several hospitals across China. Results were analyzed using descriptive statistics. RESULTS: There were 942 valid questionnaires from patients from 31 provinces and cities in China, with a male-to-female ratio of approximately 1:14, a mean age of 48.81 years, and a median disease duration of 7 (4, 10) years. There were 320 valid questionnaires from rheumatologists, covering 30 provinces and cities in China, with a male-to-female ratio of approximately 0.87:1, a mean age of 48 years, and a median work duration of 10.5 (6, 15) years. The rheumatologists treated a median of 15 (11, 50) SS cases per month, and the median proportion of SS to all rheumatic diseases was 6.66% (6-10%). Many patients believed TCM could cure the root of the disease, and the most expected TCM therapies were TCM patent prescriptions and medicinal teas. Conversely, rheumatologists placed high value on the efficacy of TCM, and most commonly prescribed Chinese herbal decoctions. Most doctor-patient groups were positive about TCM treatment, citing the low side effects as the major advantage. Regression analysis showed that for patients over 40 years old with a course of disease > 4 years, the probability of using TCM has increased by 1-6 times; the probability of recommending TCM in clinical work of doctors who have worked for more than 15 years, TCM and integrated traditional Chinese and western medicine has increased 1-2 times. CONCLUSIONS: TCM has become widely accepted and earned attention from doctor-patient groups, especially among older patients and experienced rheumatologists. However, negative prejudices and absence of accurate information about TCM treatments and SS itself require improvement. The contradiction between TCM dosage form and efficacy is a major problem, and patient demand for convenient and efficient TCM patent preparations suggests future work should focus on developing TCM patent preparations with clear compositions and mechanisms.

[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.

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.

Characteristics of patients with initial diagnosis of systemic lupus erythematosus in emergency department and their outcomes: a retrospective single-center study.

STUDY OBJECTIVE: This study aims to investigate the characteristics of patients with an initial diagnosis of systemic lupus erythematosus (SLE) in an emergency department (ED) and their outcomes. METHODS: A total of 147 SLE patients (119 females and 28 males, mean age 26 ± 19 years) who visited the ED of the Peking University People's Hospital between January 2017 and June 2022 were enrolled in the study. Data on demographic information, clinical characteristics, comorbidities, therapy, and outcomes were collected. RESULTS: Most patients visit ED because of symptoms related to SLE (74.8%, 110/147). The remaining 37 patients (25.2%) visited ED due to infection (43.2%, 16/37), gastrointestinal bleeding (10.8%, 4/37), coronary heart or cerebrovascular disease (18.9%, 7/37), macrophage activation syndrome or thrombotic microangiopathy (18.9%, 7/37), leukemia (5.4%, 2/37), and hepatic encephalopathy (2.7%, 1/37). Of the patients, 54.4% (80/147) were first diagnosed with SLE at the time of their ED visit. Thrombocytopenia events occurred significantly more frequently in this group of patients (OR 3.664, 95% CI 1.586-8.464, p = 0.002). Pulse steroid therapy was administered to 32.5% (26/80) of the patients with an initial diagnosis of SLE, and 26.3% (21/80) of these patients also received IVIG therapy during their ED visit. SLEDAI scores were significantly decreased after 6 months of therapy. The rate of mortality was 6.8% (10/147) in the 6-month follow-up period, and all the ten deaths happened in patients with disease-established SLE. The main causes of death were infections (two patients) and SLE flare (four patients). CONCLUSION: Understanding disease patterns can contribute to physicians providing accurate diagnosis and efficient care for SLE patients in ED. Key Points • Systemic lupus erythematosus, a complex autoimmune disorder, can have either a chronic or a relapsing and remitting disease course. The disease can involve acute events or severe comorbidities, and frequent visits to the emergency department (ED) are inevitable. • It is essential to better understand which comorbidities can lead to emergency department visits. Accurate clinical diagnosis and appropriate interventions from ED physicians can have a strong impact on the prognosis of the disease. • Hematologic compromise attributed to SLE flare is the most common reason for ED visits. Owing to aggressive treatments, the clinical outcomes in patients with initial diagnosis of SLE have improved notably. • Our study highlights that early recognition and appropriate management of SLE-related conditions and other comorbidity in ED are crucial.

Aberrant Immune Features after Recovery from COVID-19 in Patients with Systemic Lupus Erythematosus and Other Autoimmune Diseases.

Considering the large number of individuals who have already been infected and may have reinfection, the post-infection effects of COVID-19 are of great importance for clinical practice and predicting disease trends. However, our understanding of the potential long-term effects, particularly on immunity, after recovering from COVID-19 remains limited. The aim of this study was to investigate the abnormal immunological factors that contribute to the prolonged immunological effects of COVID-19. Two groups of patients were enrolled in the study, including 11 individuals with various autoimmune diseases (AIDs) and 16 patients diagnosed with systemic lupus erythematosus (SLE). Detailed clinical symptoms were closely monitored, and peripheral mononuclear cells were analyzed using flow cytometry. The clinical status was evaluated using the SLE Disease Activity Index (SLEDAI) and the Clinical Global Impressions (CGI) index. The proportions of follicular T helper cells (Tfh) exhibited significant increases in both cohorts (AID: p = 0.03; SLE: p = 0.0008). Conversely, the percentages of Foxp3+ and CD4+ regulatory T cells (Treg) were reduced in patients following COVID-19 infection (AID: p = 0.009, 0.05, resp.; SLE: p = 0.02, 0.0009, resp.). The percentages of Th2 and Th17 cells were significantly increased in SLE patients (p < 0.05). Exacerbated conditions were observed in SLE patients two months after infection (SLEDAI, p < 0.05). Our findings show that COVID-19 infection increases Tfh cells and decreases Treg cells in patients of AIDs, worsening pathogenetic immune status in post-recovery populations.

A spiropyran-based polymer with a stimulus response to water temperature and water content.

Temperature-responsive spiropyran-functionalized polymers usually require a thermo-sensitive polymer. However, their temperature response range is limited by the lower critical solution temperature (LCST) of the thermo-sensitive polymer, which does not exceed 37 °C. In this work, a hydrophilic polymer (PHEA-SP) sheet was prepared by photo-initiated copolymerization of hydroxyethyl acrylate (HEA) and a spiropyran crosslinking agent (SP). In water, swelling and hydrogen bonding can increase the ring-opening isomerization probability of spiropyran at the PHEA-SP crosslinking point, thus amplifying the discoloration of spiropyran induced by temperature change. PHEA-SP is very responsive to water temperature in the range of 25-55 °C, due to the amplification of spiropyranoid discoloration described above. This method avoids the dependence of the temperature responsive spiropyran-functionalized polymer on a thermo-sensitive polymer and additional UV light, while increasing the upper limit of the water temperature response to 55 °C. In addition, PHEA-SP also shows responsivity to water content in ethanol solution from 0.3% to 100%.

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.

Spiropyran-Based Soft Substrate with SPR, Anti-Reflection and Anti-NRET for Enhanced Visualization/Fluorescence Dual Response to Metal Ions.

The photoluminescence of modified spiropyran on solid surfaces is poor, and the fluorescence intensity of its MC form is weak, which affects its application in the field of sensing. In this work, a PMMA layer containing Au nanoparticles and a spiropyran monomolecular layer are coated on the surface of a PDMS substrate with inverted micro-pyramids successively by means of interface assembly and soft lithography, and the overall structure is similar to insect compound eyes. The anti-reflection effect of the bioinspired structure, the SPR (surface plasmon resonance) effect of the Au nanoparticles and the anti-NRET (non-radiation energy transfer) effect of the PMMA isolation layer raise the fluorescence enhancement factor of the composite substrate vs. the surface MC form of spiropyran to 5.06. In the process of metal ion detection, the composite substrate can achieve both colorimetric and fluorescence response, and the detection limit for Zn2+ can reach 0.281 µM. However, at the same time, the lack of the ability to recognize specific metal ions is expected to be further improved by the modification of spiropyran.

Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration.

BACKGROUND: The aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients. METHOD: Patients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated. RESULT: In total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116-8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ. CONCLUSION: We provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations.

Purtscher-like retinopathy associated with systemic lupus erythematosus treated with rituximab plus low-dose interleukin-2: A case report.

Purtscher-like retinopathy, an occlusive microvasculopathy, is a rare and severe ophthalmic complication of systemic lupus erythematosus (SLE) characterized by a sudden loss of vision with retinal whitening, cotton wool spots and minimal intraretinal hemorrhage. Recovery in visual acuity is usually poor even with prompt treatment. This case showed a patient with SLE concurrent Purtscher-like retinopathy treated with rituximab and interleukin-2 (IL-2) with good prognosis. A 16-year-old female with a 2-year history of SLE was admitted because of unrelieved disease activity of SLE when treated with a high dose of corticosteroids and immunosuppressants and she further suffered from reduced visual acuity in both eyes. She was diagnosed with Purtscher-like retinopathy secondary to SLE after ocular examination. Rituximab and low-dose IL-2 for systemic treatment and intravitreal injection of anti-vascular endothelial growth factor antibody to right eye were given. The SLE disease was completely relieved with the sight recovering and no recurrence of Purtscher-like retinopathy was reported during 6-year follow-up. Purtscher-like retinopathy associated with SLE should be treated early and promptly. Rituximab should be considered in SLE patients with Purtscher-like retinopathy who have an incomplete response to initial immunosuppressive therapy and low-dose IL-2 may help induction of clinical remission.

Anti-carbonic anhydrase II antibody reflects urinary acidification defect especially in proximal renal tubules in patients with primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is a systemic autoimmue disease featured by excessive autoantibody production. It has been demonstrated that anti-carbonic anhydrase II (anti-CA II) antibody is correlated with renal tubular acidosis in pSS; however, no further details about urinary acidification defect have been reported, and the antibody's relationship with other organ impairments remains unknown. This case-control study aimed to examine anti-CA II antibody levels in relation to various systemic complications in pSS, and evaluate its potential role as a organ-specific biomarker in a Chinese cohort. Serum anti-CA II antibody levels were determined using ELISA in 123 patients with pSS and 72 healthy controls. The medical records of the patients were collected, and the correlation between serum anti-CA II antibody and clinical/immunological parameters was investigated. Serum anti-CA II antibody level and its positive rate were significantly increased in pSS patients compared with controls, and ANA-positive patients presented even higher titers of the antibody. In anti-CA II positive group, remarkably higher urine pH and bicarbonate, as well as lower urine titratable acid and serum potassium were observed, which indicated renal tubular acidification dysfunction both involving bicarbonate reabsorption and acid secretion. In addition, platelet count and complement 3, complement 4 levels decreased, whereas serum IgG, IgA and γ-globulin levels increased notably in accord with a higher EULAR SS disease activity index score in these patients. Further analysis showed that anti-CA II antibody was most elevated in patients with defect in bicarbonate reabsorption, reflecting proximal renal tubular injury, rather than in patients with distal renal tubular acidosis as previously reported. In conclusion, anti-CA II antibody reflects renal (especially proximal renal tubular) and hematologic impairment as well as increased disease activity in pSS. It may act as a serum biomarker of systemic damage of pSS.

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.

Clinical characteristics of rheumatic disease-associated hypophysitis: A case series and review of literature.

Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.

Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome: A Randomized Clinical Trial.

Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches. Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People's Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020. Interventions: Patients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up. Main Outcomes and Measures: The primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24. Results: Sixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, -18.33 points; 95% CI, -28.46 to -8.21 points; P = .001; pain: difference, -10.33 points; 95% CI, -19.38 to -1.29 points; P = .03; fatigue: difference, -11.67 points; 95% CI, -20.65 to -2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells. Conclusions and Relevance: In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells. Trial Registration: ClinicalTrials.gov Identifier: NCT02464319.

Tonsillar Microbiome-Derived Lantibiotics Induce Structural Changes of IL-6 and IL-21 Receptors and Modulate Host Immunity.

Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin-21 (IL-21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL-6 and IL-21 receptors, thereby inhibiting the bindings of IL-6 and IL-21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides-mediated immunomodulation.

Antiphospholipid Syndrome-Related Pulmonary Embolism: Clinical Characteristics and Early Recognition.

Background: Pulmonary thromboembolism is a common disease frequently encountered in the emergency room and has a high mortality rate. Antiphospholipid syndrome (APS) is a high-risk factor for recurrent pulmonary embolism (PE). It is critical to effectively administer anticoagulants to avoid the recurrence of thrombotic events. This study aims to identify the clinical characteristics of APS patients with PE (APS-PE) and to develop a risk score for determining the presence of APS in PE patients in the emergency situations. Methods: We retrospectively enrolled 76 PE patients in this study, with 46 patients in the APS-PE group and 30 patients in the non-APS-PE group. We compared differences in demographics, laboratory parameters, and early mortality risk between the two groups. Risk factors for APS-PE were screened using logistic regression analysis. We also developed an early risk score using multivariate analysis weighted points proportional to the ß- regression coefficient values and calculated the sensitivity and specificity for APS in PE patients. Results: In the APS-PE group, we observed a higher proportion of males (43.6 vs. 20%), a higher proportion of low-risk patients (58.7 vs. 10%), lower levels of white blood cells and platelets (PLT), longer activated partial thromboplastin time (APTT), and a slight increase in D-dimer levels. Patients who were triple positive for antiphospholipid antibodies (aPLs) were younger. The APTT gradually increased as the number of positive aPLs increased. The risk factors for APS included male (OR = 5.565, 95% CI 1.176-26.341), decreased PLT (OR = 0.029, 95% CI 0.003-0.330), slightly increased D-dimer (OR = 0.089, 95% CI 0.019-0.426), and prolonged APTT (OR = 4.870, 95% CI 1.189-19.951). The risk score was named MPDA and included male, PLT, D-dimer and APTT, which can predict APS in PE patients with the AUC at 0.888 (95% CI 0.811-0.965). Conclusion: The risk factors for APS in PE patients are male, low PLT, prolonged APTT and slightly increased D-dimer. The MPDA is a quantitative scoring system which is highly suggestive of APS in PE patients.

The COVID-19 vaccine: Attitudes and vaccination in patients with autoimmune inflammatory rheumatic diseases.

Background: We examined attitudes toward the COVID-19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods: A multicenter, web-based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results: Of the unvaccinated patients, 32.9% were willing to receive the COVID-19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine-related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID-19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow-up of 88 (38, 131) days, patients' disease activities were stable. Conclusions: The findings show that AIIRD patients were unwilling to receive the COVID-19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID-19 disease and vaccines had a significant effect on vaccination willingness.