Antibody-positive Group Research Articles

Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin.

Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD). We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin. Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD. IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

The association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome.

This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome (pSS). A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti-Ro/SSA and anti-La/SSB, whereas 97 had anti-Ro/SSA but not anti-La/SSB antibodies. Forty-four patients for whom neither anti-Ro/SSA nor anti-La/SSB antibodies were found were diagnosed with Sjögren's syndrome by minor salivary gland biopsy. The anti-Ro/SSA antibody-positive group showed higher rheumatoid factor (RF) levels than the anti-Ro/SSA antibody-negative group. The anti-La/SSB antibody-positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti-La/SSB antibody-negative group. In addition, the group with both anti-Ro/SSA and anti-La/SSB antibodies showed lower UWS than the group with only anti-Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C-reactive protein. UWS and SWS were lower when a patient was positive for anti-La/SSB, showing that anti-La/SSB is more likely to be involved in salivary gland hypofunction than anti-Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti-La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS.

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

To summarize the clinical, serological, and radiological characteristics of anti-synthetase syndrome (ASS) patients with different anti-aminoacyl-tRNA synthase antibody. 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. 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). 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.

Presence of anti-nuclear antibody associated with worse clinical outcomes of anti-NMDAR encephalitis.

PurposeSystemic autoantibodies are important for the diagnosis of autoimmune diseases, but their roles in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are unknown. The purpose of our study is to investigate the characteristics and a prognosis of anti-NMDAR encephalitis with the prevalence of autoantibodies.MethodsSystemic autoantibodies were evaluated in 64 patients with anti-NMDAR encephalitis and 14 patients with autoimmune encephalitis with other forms. Then, according to systemic autoantibodies, patients with anti-NMDAR encephalitis were divided into an anti-nuclear antibody (ANA) positive group and an ANA negative group. The clinical outcome was assessed by a modified Rankin score at 12 months after the disease onset.ResultsA total of 64 patients with anti-NMDAR encephalitis were enrolled, of which 28.13% (18/64) were positive for ANA. The titers of a positive anti-NMDAR antibody in CSF (p = 0.041) and serum (p = 0.031) in the ANA-positive group were significantly higher than the ANA-negative group. Patients with ANA positive than those with ANA negative showed lower rates of headache (p = 0.047) and speech disorder (p = 0.049). The presence of ANA was associated with a worse clinical outcome at 12 months (p = 0.043).ConclusionANA was prevalent in patients with anti-NMDAR encephalitis, and associated with a worse prognosis and impaired neurological recovery.

Association of anti-citrullinated peptide antibodies with the progression of aortic stenosis

Abstract Background/Purpose Aortic stenosis (AS) is common in an aging population, but disease activity biomarkers are lacking. The pathophysiology of calcific AS shares many similarities with atherosclerosis, including lipid deposition, inflammation, and calcification. Citrullination is a part of many chronic inflammatory processes and citrullinated proteins have been found within atherosclerotic plaque. Thus, we investigated whether the presence of anti-citrullinated peptide antibody, especially anti-CCP antibody, might be associated with AS. Methods A retrospective observational study was conducted for 678 patients who underwent echocardiography and anti-CCP antibody test between April 2004 and July 2020. Anti-CCP antibody status was regarded as positive when concentrations exceeded the upper limit of normal (ULN), and any lower value was considered negative. The anti-CCP antibody-positive group was subdivided into two groups: low-positive for ≥ ULN but &amp;lt; the median, and high-positive ≥ the median value (Figure 1A). Also, aortic valve (AV) tissues were obtained from the patients with AS or not at the time of surgical aortic valve replacement or heart transplantation, who did not have rheumatoid arthritis. We analyzed the presence of citrullinated proteins in the AV by immunohistochemistry and Western blotting. Results 241 (35.5%) subjects showed AV degeneration in baseline echocardiography. They had a higher anti-CCP antibody positivity rate (42.7% vs. 34.6%, p=0.035) than the subjects without AV degeneration. Of total patients, 331 (48.8%) subjects underwent follow-up echocardiography (median follow-up duration 4.6 years [interquartile range 2.0–8.0 years]). AS progression, which was defined as an increase of at least one grade in AS severity classification on follow-up echocardiography, was observed in 34 (10.3%) patients. The progression of AS occurred more in the high-positive group than in the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p=0.041) (Figure 1B). In multivariate analysis, the high-positivity of anti-CCP antibody was an independent predictor of AS progression (Odds ratio: 2.312; 95% confidence interval: 1.006–5.310; p=0.048) (Figure 1C). Increased citrullination was visualized in areas with diseased AV compared with normal AV tissue by immunohistochemistry (Figure 2A, 2B) and Western blotting (Figure 2C, 2D). These results suggested the possible association with the citrullinated peptide-related inflammation process and the pathophysiology of AS. Conclusion A positive result of anti-CCP antibody, especially with a high titer, was associated with AV degenerative change at baseline echocardiography. Also, anti-CCP antibody positivity was an independent factor for predicting the progression of AS. These findings suggest that citrullination can be a part of the pathophysiology of AS. Furthermore, the anti-CCP antibody can be a biomarker predicting AS progression. Further research will be needed. Funding Acknowledgement Type of funding sources: None.

Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.

Investigation of the Relationship Between the Immune Responses due to COVID-19 Vaccine and Peripheral Bloodlymphocyte Subtypes of Healthcare Workers

Worldwide vaccination is the best strategy to limit the Coronavirus disease-2019 (COVID-19) pandemic. The aim of this study was to investigate the antibody levels and hemogram parameters and the prediction of T-helper, T-cytotoxic and B lymphocyte subtypes in the peripheral blood for the development of these antibodies in the selected group of healthcare workers who were vaccinated with CoronaVac® (Sinovac, China). In a previous study with the same researchers, blood samples were taken from healthcare workers one month after the second vaccination, and anti-RBD anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) IgG antibodies were measured by enzyme linked immunosorbent assay (ELISA) method. Test results were classified as binding antibody <25.6 BAU/mL unresponsive, 25.6-35.1 BAU/mL weak response, <35.2 BAU/mL strong response, according to the assay manufacturer's recommendations. According to these criteria, it was determined that 22 (8.3%) people had no response, 25 (9.5%) people had a moderate response, and 217 (82.2%) people had a strong response. According to these results, 30 people from each group were invited. The results of three individuals were excluded from the evaluation due to chronic illness. A total of 87 health workers were included in the study. Twenty-two of these people had no response, 25 had a moderate response, and 40 had a good response. Flow cytometry was used to examine the peripheral blood lymphocyte percentage distribution. Statistical analyzes were performed with SPSS 26 software. The conformity of the variables to the normal distribution was examined using analytical methods (Kolmogorov-Smirnov/ Shapiro-Wilk tests). Pearson's Chi-square test was used to compare categorical variables. The correlation between the antibody level and the measurement results of hemogram parameters and lymphocyte indicators was evaluated by Pearson's correlation analysis. The model was established by performing linear regression analysis with the variables correlated with the antibody level. Cases with a p value below 0.05 were considered statistically significant. The age range of the participants in the study was 22-69. The mean age was 45.5 ± 10.4 years. Antibodies against SARS-CoV-2 virus were detected by ELISA method in 65 (74.7%) of the healthcare professionals, while no antibodies were detected in 22 (25.3%) of them. Lymphocyte count (p= 0.002), CD3 count (p= 0.0004), CD4 count (p= 0.0001), CD3/CD19 ratio (p= 0.011), CD4 percentage (p= 0.004) in the antibody positive group was found to be significant. According to the level of correlation between antibody level and lymphocyte indicators, a statistically significant negative correlation was found in CD3, CD4, CD8 and CD19 positive lymphocytes, respectively, and the best correlation was observed in CD3 positive lymphocytes. The formula f (Antibody level)= y= 358002 -0.176 x CD3 + 0.469 x CD19 was created using the linear regression model. In the light of the data of this study, the central role of T and B cells in COVID-19 immunization emerges. The vaccine-related antibody level-related formula may be useful for healthcare professionals in patient follow-up. It is thought that conducting vaccine related immune response studies involving larger populations will contribute more to the literature.

OP-9 - Correlation between antiphospholipid antibodies and the coagulation-fibrinolysis system in women with a history of miscarriage - comparison between conventional antiphospholipid antibodies and neo-self antibodies.

The clinical diagnostic criteria for antiphospholipid antibody syndrome (APS) include thrombosis and obstetric complications; alterations in the coagulation-fibrinolysis system due to pathogenic autoantibodies have been described as a common background for the clinical presentation of APS. Recently, autoantibodies against β2-glycoprotein I (β2GPI) in complex with HLA class II molecules (β2GPI/ HLA-DR) (neo-self antibodies) have been reported to be a novel autoantibody associated with APS. The present study investigated the relationship between conventional antiphospholipid antibodies and neoself antibodies and coagulation/fibrinolysis markers in women with a history of miscarriage. Serum antibody titres of conventional antiphospholipid antibodies (anti-cardiolipin IgG/IgM, anti-β2GPI and lupus anticoagulant) and neo-self antibodies were measured in 58 women with a history of miscarriage. Coagulation and fibrinolysis status was assessed by TAT, AT and D-dimer and APTT. In addition, the relationship with subsequent pregnancy outcome was investigated. Ten women were positive for conventional antiphospholipid antibodies and six were positive for neo-self antibodies, including one patient who was positive for both. 28 patients had elevated TAT levels and none of them showed APTT elongation. The frequency of elevated TAT was 80% (8/10) in the conventional antiphospholipid antibody-positive group and 83% (5/6) in the neo-self antibody-positive group. Those ratios were higher than the TAT positivity of 37% (16/43) in the antibodies-negative group. During the observational period, clinical pregnancy was confirmed in 23 cases, including 16 with TAT elevation. Among them, three cases resulted in early miscarriage, two of which had a TAT elevation, one of which was positive for neo-self-antibodies. Both the traditional antiphospholipid antibody-positive group and the neo-self antibody-positive group had a high frequency of TAT elevation. Alteration in coagulation/fibrinolytic system could be shared as the pathogenic background between the two groups and is possibly involved in the incidence of miscarriage.

Seroprevalence of Anti-Hepatitis E Virus Antibodies among Patients from a Tertiary Hospital from Northeast Romania.

Background and Objectives. Being an enterically transmitted pathogen with a growing prevalence in developed countries, hepatitis E virus (HEV) infection remains an underdiagnosed disease in Eastern Europe. As far as Romania is concerned, only a few studies address this issue. Our goal was to estimate the prevalence of serum anti-HEV IgA/IgM/IgG antibodies in a group of patients admitted to the Clinical Hospital for Infectious Diseases “St. Parascheva” Iasi. Materials and Methods. The cross-sectional study consisted of enrollment of 98 patients admitted to the clinic for COVID-19 over a period of three months in 2020. Results. The median age in our study was 73 years, with an equal gender ratio and with a predominance of people from the urban environment (75%). The overall HEV antibody seroprevalence was 12.2%. The main risk factors associated with HEV infection were consumption of water from unsafe sources (58.3% HEV-positive patients vs. 26.7% HEV-negative patients, p = 0.026) and improperly cooked meat (58.3% HEV-positive patients vs. 23.2% HEV-negative patients, p = 0.01). Zoonotic transmission was an important criterion in our study, with patients reporting contact with pigs, poultry, rats, or other farms animals, but no significant differences were found between HEV antibody positive and negative groups. Conclusions. The seroprevalence rate of HEV antibodies was similar to other previous reports from our area but higher than in most European countries. The fact that HEV antibodies were detected in patients without identifiable risk factors for hepatitis E is evidence of subclinical infection as a silent threat.

Relationships between the serum TPOAb and TGAb antibody distributions and water iodine concentrations, thyroid hormones and thyroid diseases: a cross-sectional study of 2503 adults in China.

The aim of this study was to explore the status of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in three areas with differing water iodine concentrations; and to discuss the relationships between these two thyroid antibodies and thyroid diseases in the three areas. We investigated 2503 adults from three areas. Urinary iodine concentrations, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), TPOAb, TGAb and thyroid volume (TV) were measured, and thyroid ultrasonography was performed. The positivity rates of TGAb(+), TPOAb(+) and TGAb(+) and TPOAb(+) or TGAb(+) were significantly higher in iodine fortification (IF) areas than iodine adequate (IA) areas (all P < 0·05). In IF and iodine excess areas, the positivity rates of TPOAb(+), TGAb(+) and TPOAb(+) or TGAb(+) significantly increased with age (all P for trend < 0·05). The levels of TSH, TV and the prevalence of overt hypothyroidism, subclinical hypothyroidism and goitre were significantly elevated in the thyroid antibody-positive groups in the three areas, but the FT3 was diminished (all P < 0·010). Positivity for TPOAb and TGAb was associated with an increased risk of subclinical hypothyroidism in the three areas. In areas with different median water iodine, positivity for both TPOAb and TGAb was associated with elevated TSH values. Notably, with the increased levels of TPOAb, the frequency of abnormally elevated TSH increased dramatically in the three areas.

Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study.

Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15-41] vs. 19 [5-30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes

IntroductionMaternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. MethodsWe performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. ResultsThe median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DiscussionSARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

Characteristics and Prognosis of Antibody Non-responders With Coronavirus Disease 2019.

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally. Information regarding the characteristics and prognosis of antibody non-responders to COVID-19 is limited.MethodsIn this retrospective, single-center study, we included all patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1,921 patients were divided into the antibody-negative (n = 94) and antibody-positive (n = 1,827) groups, and 1:1 propensity score matching was used to match the two groups.ResultsIn the antibody-negative group, 40 patients (42.6%) were men, and 49 (52.1%) were older than 65 years. Cough was the most common symptom in the antibody negative group. White blood cell counts, neutrophils, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, urea nitrogen, and creatinine were significantly higher in the antibody-negative patients than in the antibody-positive group (P < 0.005). The number of days of nucleic acid-negative conversion in the antibody-negative group was shorter than that in the antibody-positive group (P < 0.001). The hospitalization time of the antibody-negative patients was shorter than that of the antibody-positive patients (P < 0.001).ConclusionSome COVID-19 patients without specific antibodies had mild symptoms; however, the inflammatory reaction caused by innate clinical immunity was more intense than those associated with antibodies. Non-specific immune responses played an essential role in virus clearance. There was no direct correlation between excessive inflammatory response and adverse outcomes in patients. The risk of reinfection and vaccination strategies for antibody-negative patients need to be further explored.

Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Effects of maternal antibodies in infants on the immunogenicity and safety of inactivated polio vaccine in infants

ABSTRACT The presence of maternal poliovirus antibodies may interfere with the immune response to inactivated polio vaccine (IPV), and its influence on the safety of vaccination is not yet understood. A total of 1146 eligible infants were randomly assigned (1:1) to the IPV and Sabin IPV (SIPV) groups to compare and analyze the efficacy of the two vaccines in preventing poliovirus infection. We pooled the SIPV and IPV groups and reclassified them into the maternal poliovirus antibody-positive group (MAPG; ≥1: 8) and the maternal poliovirus antibody-negative group (MANG; <1: 8). We evaluated the impact of maternal poliovirus antibodies by comparing the geometric mean titer (GMT), seroconversion rate, and geometric mean increase (GMI) of types I–III poliovirus neutralizing antibodies post-vaccination, and incidence rates of adverse reactions following vaccination between the MAPG and MANG. Respective seroconversion rates in the MAPG and MANG were 94% and 100%, 79.27% and 100%, and 93.26% and 100% (all serotypes, P < .01) for types I—III poliovirus, respectively. The GMT of all types of poliovirus antibodies in the MAPG (1319.13, 219.91, 764.11, respectively) were significantly lower than those in the MANG (1584.92, 286.73, 899.59, respectively) (P < .05). The GMI in the MAPG was significantly lower than that in the MANG (P < .05). No statistically significant difference in the incidence of local and systemic adverse reactions was observed between the MAPG and MANG. Thus, the presence of maternal poliovirus antibodies does not affect the safety of IPV but can negatively impact the immune responses in infants after IPV vaccination.

Clinical characteristics of anti-isoleucyl-tRNA synthetase antibody associated syndrome and comparison with different patient cohorts.

This study aimed to analyse the clinical features of anti-isoleucyl-tRNA synthetase (OJ) antibodies in Chinese patients and to compare with previously published cohorts. We reviewed the clinical data of anti-OJ antibody positive patients, including their long-term follow-up. Anti-OJ antibodies were present in 10 of 1269 (0.8%) patients with idiopathic inflammatory myopathies (IIMs), and 10/320 (3.1%) patients with anti-synthetase syndrome (ASS). Of the anti-OJ antibody-positive patients, 90% had interstitial lung disease (ILD), of whom three (30%) developed rapidly progressive ILD (RP-ILD). Half (50%) of the patients were febrile and developed myocardial involvement; 40% of patients experienced myositis, mechanic's hands and arthritis. Compared to the anti-Jo-1 group, the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the anti-OJ antibody-positive group were higher (p<0.05). From a review of the literature regarding the clinical features of anti-OJ, fever was more common in the eastern cohort (41.7% vs. 8.3%, p=0.002), whereas patients in western countries were more likely to develop arthritis (20.9% vs. 58.1%, p=0.001). With complete follow-up of the present cohort, 80% improved with treatment, including one patient who underwent lung transplant. The anti-OJ antibody occurred infrequently in Chinese patients, ILD was the major clinical feature, but myocardial injury was also a prominent associated complication. Anti-OJ positive patients were responsive to treatment.

Characteristics of Triple Seronegative Myasthenia Gravis: A Single Center Experience

Background: There is variability in the literature regarding the characteristics of triple seronegative myasthenia gravis (SNMG) patients. Most studies were performed before LRP4 antibodies were discovered, and characterizations of triple seronegative patients are lacking in the literature.&#x0D; Methods: We retrospectively investigated patients diagnosed with myasthenia gravis (MG) at Ohio State University from 2009 to 2019. Triple SNMG was defined by a history and examination that was consistent with MG and positive SFEMG, RNS or edrophonium testing, but negative serology for AChR, MUSK, and LRP4 antibodies.&#x0D; Results: A total of 210 AChR+, 9 MuSK+, 6 LRP4+, 9 double SNMG, and 21 triple SNMG patients were reviewed. Triple SNMG patients required significantly fewer immunosuppressive agents compared with AChR+ patients (p=0.0001) and a trend towards a less frequent history of hospitalizations, myasthenic crises and intubations compared to all antibody positive groups. Triple SNMG patients had a significantly higher frequency of ocular disease (33%) compared to AChR+ patients (13%) (p=0.0250). One triple and one double SNMG patient had thymic hyperplasia and improved after thymectomy. 11 triple SNMG patients had negative genetic testing for CMS.&#x0D; Conclusion: Our results further elucidate the clinical characteristics of triple SNMG, which include the predominance for ocular disease and a less severe disease course. Although likely rare, investigation for thymic pathology should be a consideration even in SNMG, and thymectomy should be considered when there is thymic pathology. We did not find alternate diagnoses in SNMG patients and thus ancillary testing should be considered in carefully selected patients for cost-effective care.

Abstract 43: Prevalence of islet-autoantibodies and monogenic diabetes in children with recent onset type 1 diabetes mellitus: A multicenter study

Background: Previous smaller studies have shown higher prevalence of islet-antibody negative Type 1 diabetes mellitus (T1DM) among Indians compared to Caucasians. Islet-antibody negative (Type 1B) diabetes is not well characterized.Aims and Objectives: To study the prevalence of islet-autoantibodies, characterize type 1B diabetes, and determine the role of enterovirus infections and monogenic diabetes in children and adolescents with recent onset T1DM.Results: Among 111 patients, frequency of islet-autoantibody positivity were: GAD65-73%, IA2-35% and ZnT8-34%. 20 (18%) were negative for all 3 islet-autoantibodies. There were no significant clinical, biochemical or HLA allelic frequency differences between antibody negative and positive group. None of the ninety subjects tested showed evidence of enterovirus infection in serum by RT-PCR. Of the seven Type 1B patients without ketoacidosis tested, 2 had pathogenic mutations: one each in WFS 1 [homozygous c.2006A>G (p.Tyr669Cys)] and HNF4a [heterozygous c.998G>A (p.Arg333His)] loci. An additional 2 subjects had mutations of uncertain significance: one each in WFS 1 [heterozygous c.1522_1523del (p.Tyr508CysfsTer34)] and ABCC 8 [Heterozygous c.3784G>A (p.Ala1262Thr)] loci.Conclusions: A significant proportion of patients with T1DM were negative for islet antibodies at onset, but did not differ clinically or biochemically. Monogenic diabetes was found in a proportion of patients with type 1B diabetes.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P &lt; 0.01) and anti-Jo1 (64.9%, P &lt; 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P &lt; 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P &lt; 0.05). Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.