[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.

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.

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%.

Immune responses after influenza vaccination in patients of primary Sjögren's syndrome.

OBJECTIVES: Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren's Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination. METHODS: A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored. RESULTS: The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P<0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P<0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P>0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS. CONCLUSION: Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.

Interleukin 17E associates with haematologic involvement and autoantibody production in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis.

Corneal nerve structure in patients with primary Sjögren's syndrome in China.

BACKGROUND: The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren's syndrome in China. METHODS: This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren's syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. RESULTS: SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P < 0.001 and P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = - 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = - 0.534, P = 0.013 and r = - 0.487, P = 0.025, respectively). CONCLUSIONS: Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. METHODS: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. RESULTS: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. CONCLUSIONS: Low-dose IL-2 might be effective and tolerated in treatment of SLE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

Anti-recoverin antibodies indicate fundus abnormalities in systemic lupus erythematosus.

OBJECTIVES: Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities. METHODS: Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records. RESULTS: Compared with the non-fundus group, the fundus group had a higher incidence of hematuria (p < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74, p < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group (p = 0.029) or the healthy control group (p = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37, p < 0.05). CONCLUSIONS: Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.

Evaluation of soluble CD25 as a clinical and autoimmune biomarker in primary Sjögren's syndrome.

OBJECTIVES: Serum soluble CD25 (sCD25) is associated with T cell activation and regarded as a marker of disease activity in autoimmune disorders. The purpose of our study was to investigate the clinical relevance of sCD25 in patients with primary Sjögren's syndrome (pSS). METHODS: Sixty-five pSS patients and 60 healthy controls (HCs) with comparable age and gender were recruited. Serum samples were collected and sCD25 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory changes were examined after 12 weeks of treatment, and data were recorded in detail. The European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI) was used to evaluate disease activity. RESULTS: Serum sCD25 levels were significantly increased in pSS patients, compared to HCs (p<0.001). The increased sCD25 were positively associated with ESSDAI scores (p=0.006), especially the haematological domain (p=0.002), and erythrocyte sedimentation rate, and levels of C-reactive protein, immunoglobulin G and γ-globulin (p<0.001, <0.001, 0.045 and 0.011, respectively). High sCD25 was strongly associated with anaemia (p=0.014) and was inversely correlated with haemoglobin levels (p=0.002). In further analysis, we found that patients with autoimmune haemolytic anaemia (AIHA) had the highest levels of sCD25, followed by patients with chronic disease of anaemia (ACD) and iron-deficiency anaemia (IDA). With the improvement after treatment, serum sCD25 levels were significantly decreased, accompanied by resolved anaemia compared to baseline (p=0.001). CONCLUSIONS: sCD25 was associated with disease severity, especially anaemia in patients with pSS and may serve as an indicator of disease activity.

[Analyses of 77 patients with hemophagocytic syndrome].

OBJECTIVE: To summarize the clinical features and laboratory data of 77 patients with hemophagocytic syndrome (HPS). METHODS: A total of 77 patients of HPS were continuously collected from 2007 to 2014 at our hospital. Their underlying diseases, clinical features, laboratory data, therapy and prognosis were analyzed. RESULTS: Their The patients aged from 3 months to 85 years. The gender ratio was roughly equal. Primary HPS was diagnosed in only 5 cases by gene detection Another 72 cases belonged to secondary HPS. The causes were infection (n = 28), hematologic neoplasm (n = 25), autoimmune diseases (AID, n = 11) and unknown (n = 8). HPS was the initial symptom in nearly half cases of hematologic neoplasm and AID. HPS was characterized by high fever (100%), hypersplenomegaly (81.8%) and lymphadenopathy (40.3%). Laboratory data showed cytopenia (94.8%), serum ferritin elevation (93.2%), hypofibrinogenemia (61.8%), hemophagocytosis in bone marrow (78.1%) and hypertriglyceridemia (55.3%). Low NK-cell activity (95.2%) and elevation of sCD25 (100%) were specific manifestations in HPS. Pulmonary infection (36.4%) and hepatic malfunction (33.3%) were common. Approximately 70% were treated with HLH-2004. Pulse-dose corticosteroid therapy (methylprdnisolone 200-500 mg/d) was used in 8 AID patients. And 14 patients died and 10 withdrew treatment because of exacerbation. Five had complications of DIC and another 5 progressed into MODS. Neoplasm (52.0%) had the highest mortality in secondary HPS. And infection (25.0%) and AID (18.2%) followed. CONCLUSION: Sometimes HPS occurs simultaneously with autoimmune disease or neoplasm. Relevant laboratory tests for suspected patients may aid an early diagnosis. Presence of DIC or MODS in HPS is possibly correlated with a poor prognosis and a high mortality.

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.

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.

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.

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.

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.

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.

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.

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.